(S)-alpha-Methylhydrocinnamic acid [(2S)-2-Methyl-3-phenylpropanoic acid]

(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

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90 reactions in Reaxys

2018-07-27 00h:30m:54s (UTC)

O

1. Query HO

H

Search as: Product, As drawn, No mixtures ) AND (IDE.RN='14367-54-5') AND (IDE.INCHI='MCIIDRLDHRQKPHQMMMGPOBSA-N') NOT (RX.RXRN=2614110))

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

O

HO

O

OH

H

H

HO O

Rx-ID: 2062919 View in Reaxys 1/90 Yield

Conditions & References With hydrogen, <Rh2(COD)2><BF4>2, triethylamine in tetrahydrofuran, Time= 1h, p= 760Torr , Ambient temperature, different chiral catalysts, Product distribution Johnson, Thomas H.; Rangarajan, G.; Journal of Organic Chemistry; vol. 45; nb. 1; (1980); p. 62 - 65 View in Reaxys With hydrogen, di-μ-chlorobis(norbornadiene)dirhodium(I), chiral phosphinediamine in methanol, Time= 57h, T= 25 °C , p= 15001.2Torr , various solvents, pressures, times; other chiral phosphine diamine ligand, Product distribution Yamada, Issaku; Ohkouchi, Munetaka; Yamaguchi, Motowo; Yamagishi, Takamichi; Journal of the Chemical Society Perkin Transactions 1; nb. 12; (1997); p. 1869 - 1873 View in Reaxys With <RhCl(nbd)>2-(S,S)-isopropylbis<2-(1-N,N-dimethylaminoethyl)phenyl>phosphine, hydrogen in methanol, Time= 86h, T= 25 °C , p= 30400Torr , Title compound not separated from byproducts Yamada, Issaku; Yamaguchi, Motowo; Yamagishi, Takamichi; Tetrahedron Asymmetry; vol. 7; nb. 12; (1996); p. 3339 3342 View in Reaxys With hydrogen, di-μ-chlorobis(norbornadiene)dirhodium(I), (S,S)-isopropylbis<2-(1-N,N-dimethylaminoethyl)phenyl>phosphine in methanol, Time= 86h, T= 25 °C , p= 30002.4Torr , Yield given. Yields of byproduct given. Title compound not separated from byproducts Yamada, Issaku; Ohkouchi, Munetaka; Yamaguchi, Motowo; Yamagishi, Takamichi; Journal of the Chemical Society Perkin Transactions 1; nb. 12; (1997); p. 1869 - 1873 View in Reaxys With hydrogen, diacetato[(R)-(+)-2,2'-bis(diphenylphosphino)-5,5',6,6',7,7',8,8'-octahydro-1,1'-binaphthyl]ruthenium(II) in methanol, Time= 48h, p= 1140Torr , Ambient temperature, Yield given. Yields of byproduct given. Title compound not separated from byproducts Uemura, Toshitsugi; Zhang, Xiaoyoung; Matsumura, Kazuhiko; Sayo, Noboru; Kumobayashi, Hidenori; Ohta, Tetsuo; Nozaki, Kyoko; Takaya, Hidemasa; Journal of Organic Chemistry; vol. 61; nb. 16; (1996); p. 5510 - 5516 View in Reaxys With hydrogen, [Ru(η2-O2CCH3)2((S)-H8-binap)] in methanol, Time= 48h, T= 25 °C , p= 1125.09Torr , Title compound not separated from byproducts Maienza, Francesca; Santoro, Francesco; Spindler, Felix; Malan, Christophe; Mezzetti, Antonio; Tetrahedron Asymmetry; vol. 13; nb. 16; (2002); p. 1817 - 1824 View in Reaxys With (S,S)-(-)-2,2'-bis[(R)-(N,N-dimethylamino)(phenyl)methyl]-1,1'-bis[di(3,5-dimethyl-4-methoxyphenyl)phosphine]ferrocene, hydrogen, di(norbornadiene)rhodium(I) tetrafluoroborate in methanol, Time= 94h, T= 25 °C , p= 37503Torr , Title compound not separated from byproducts Spindler, Felix; Malan, Christophe; Lotz, Matthias; Kesselgruber, Martin; Pittelkow, Ulrich; Rivas-Nass, Andreas; Briel, Oliver; Blaser, Hans-Ulrich; Tetrahedron Asymmetry; vol. 15; nb. 14; (2004); p. 2299 - 2306 View in Reaxys With (R)-1,1'-di[(3,4,5-Me3C6H2)2P]-9,9'-spirobifluorene*Ru(OAc)2, hydrogen in methanol, Time= 18h, T= 25 - 28 °C , p= 4560Torr , Title compound not separated from byproducts

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

Cheng, Xu; Zhang, Qi; Xie, Jian-Hua; Wang, Li-Xin; Zhou, Qi-Lin; Angewandte Chemie - International Edition; vol. 44; nb. 7; (2005); p. 1118 - 1121 View in Reaxys With bis(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate, phosphoramidite based on chiral-3,3'-dimethylbinol, hydrogen, triphenylphosphine in water, isopropyl alcohol, Time= 16h, T= 30 °C , p= 18751.5Torr , Title compound not separated from byproducts Hoen, Rob; Boogers, Jeroen A. F.; Bernsmann, Heiko; Minnaard, Adriaan J.; Meetsma, Auke; Tiemersma-Wegman, Theodora D.; De Vries, Andre H. M.; De Vries, Johannes G.; Feringa, Ben L.; Angewandte Chemie - International Edition; vol. 44; nb. 27; (2005); p. 4209 - 4212 View in Reaxys With hydrogen, (R)-spirofluorene-[(3,4,5-Me3-C6H2)2P]2-[Ru(OAc)2] in methanol, Time= 18h, T= 25 - 28 °C , p= 4560Torr , Title compound not separated from byproducts Cheng, Xu; Xie, Jian-Hua; Li, Sheng; Zhou, Qi-Lin; Advanced Synthesis and Catalysis; vol. 348; nb. 10-11; (2006); p. 1271 - 1276 View in Reaxys With pyridylphosphorus ligand, zinc(II) salphen, hydrogen, di(norbornadiene)rhodium(I) tetrafluoroborate in dichloromethane, Time= 16h, T= 35 °C , p= 3750.3Torr , Product distribution, Further Variations: Reagents Kuil, Mark; Goudriaan, P. Elsbeth; Kleij, Arjan W.; Tooke, Duncan M.; Spek, Anthony L.; Van Leeuwen, Piet W. N. M.; Reek, Joost N. H.; Dalton Transactions; nb. 22; (2007); p. 2311 - 2320 View in Reaxys With hydrogen, triethylamine in methanol, Time= 65h, T= 25 °C , p= 4500.45Torr , Product distribution, Further Variations: Reagents Maienza, Francesca; Spindler, Felix; Thommen, Marc; Pugin, Benoit; Malan, Christophe; Mezzetti, Antonio; Journal of Organic Chemistry; vol. 67; nb. 15; (2002); p. 5239 - 5249 View in Reaxys With hydrogen, [1-[(1-Ph2P)Et]-2-(2-(3,5-(CF3)2-Ph)2-P-Ph)-ferrocene], rhodium in methanol, Time= 20h, T= 25 °C , p= 3750.38Torr , Product distribution, Further Variations: Catalysts Sturm, Thomas; Weissensteiner, Walter; Spindler, Felix; Advanced Synthesis and Catalysis; vol. 345; nb. 1-2; (2003); p. 160 - 164 View in Reaxys With hydrogen, [Ru(benzene)Cl]Cl in methanol, Time= 24h, T= 60 °C , p= 4500.45Torr , Title compound not separated from byproducts.

Qiu, Liqin; Li, Yue-Ming; Kwong, Fuk Yee; Yu, Wing-Yiu; Fan, Qing-Hua; Chan, Albert S. C.; Advanced Synthesis and Catalysis; vol. 349; nb. 4-5; (2007); p. 517 - 520 View in Reaxys C.12 :The catalyst precursor and the ligand were stirred in the solvent under argon. A solution of the substrate was added, the argon is drawn off with vacuum and the vessel is connected to a hydrogen supply at the given pressure and temperature. Switching on the stirrer starts the hydrogenation. After the given time, the stirrer is switched off and the solution is placed under argon again. Conversion and enantiomeric excess (ee) are determined by gas chromatography.

With hydrogen, bis(norbornadiene)rhodium(l)tetrafluoroborate, C40H58FeN2O3P2 in methanol, Time= 40h, T= 25 °C , p= 3750.38Torr , Product distribution / selectivity Patent; Solvias AG; WO2007/135179; (2007); (A1) English View in Reaxys With Johnson & Matthey type 440, hydrogen, cinchonidine, benzylamine in 1,4-dioxane, water, T= 23 °C , p= 760.051Torr , optical yield given as percent ee, enantioselective reaction Sugimura, Takashi; Uchida, Takayuki; Watanabe, Junya; Kubota, Takeshi; Okamoto, Yasuaki; Misaki, Tomonori; Okuyama, Tadashi; Journal of Catalysis; vol. 262; nb. 1; (2009); p. 57 - 64 View in Reaxys

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

With bis(norbornadiene)rhodium(l)tetrafluoroborate, hydrogen in tetrahydrofuran, Time= 24h, T= 20 °C , p= 7500.75Torr , optical yield given as percent ee, enantioselective reaction Lee, Jong-Dae; Thanh, Thien Co; Kim, Tae-Jeong; Sang, Ook Kang; Synlett; nb. 5; (2009); p. 771 - 774 View in Reaxys D.3 :0.41 g (2.53 mmol) of 2-methylcinnamic acid and 5 ml of degassed methanol are introduced in succession into a Schlenk vessel filled with argon. A catalyst solution consisting of 4.73 mg (0.01265 mmol) of [Rh(norbornadiene)2]BF4, 8.77 mg (0.0133 mmol) of ligand A and 5 ml of degassed methanol is prepared in a second Schlenk vessel filled with argon. This solution and the catalyst solution are then transferred in succession by means of a steel capillary into a 50 ml autoclave filled with argon.

The ratio of substrate/catalyst is 200. The autoclave is closed and a pressure of 5 bar is set by means of 4 flushing cycles (pressurization to 10 bar of hydrogen). The autoclave is thermostated at 25°C and the reaction is started by switching on the stirrer.

The reactor is stirred for 19 hours. After opening the autoclave, a reddish reaction solution is isolated. The conversion is quantitative (determined by means of GC and (at)H-NMR). Removal of the solvent on a rotary evaporator gives a quantitative yield of 2-methyl-3-phenylpropionic acid having an enantiomeric purity of 29percent ee (determined by means of HPLC after conversion into the methyl ester; column: Chiracel OB. ).

With hydrogen, bis(norbornadiene)rhodium(l)tetrafluoroborate, (S)-1-diphenylphosphino-2-[η-(S)-hydroxy-(o-diphenylphosphinophenyl)methyl]ferrocene in methanol, Time= 19h, T= 25 °C , p= 3750.38Torr , Product distribution / selectivity Patent; UMICORE AG and CO. KG; WO2005/108409; (2005); (A2) English View in Reaxys A method similar to that of Example D3 is employed. 8.96 mg (0.0133 mmol) of methoxy- TANIAPHOS are used in place of the ligand A. The conversion is 100percent. Removal of the solvent on a rotary evaporator gives a quantitative yield of 2-methyl-3-phenylpropionic acid having an enantiomeric purity of 30percent ee.

With hydrogen, bis(norbornadiene)rhodium(l)tetrafluoroborate, (S)-1-diphenylphosphino-2-[η-(S)-methoxy(o-diphenylphosphinophenyl)methyl]ferrocene in methanol, Time= 19h, T= 25 °C , p= 3750.38Torr , Product distribution / selectivity Patent; UMICORE AG and CO. KG; WO2005/108409; (2005); (A2) English View in Reaxys B.1 :The method of carrying out the hydrogenations and the determination of the optical yields ee is described in general terms

by W. Weissensteiner et al in Organometallics 21 (2002), pages 1766-1774. The catalysts are in each case prepared in situ in the solvent by mixing of the ligand and metal complex as catalyst precursor (unless indicated otherwise = [Rh(norbornadiene)2]BF4). Unless indicated otherwise, the substrate concentration is 0.25 mol/l. The determination of conversion and ee of MAA is carried out by means of gas chromatography using a chiral column (Chirasil-L-val).The hydrogenations of EAC are carried out in ethanol in the presence of 5percent (v/v) of CF3CH2OH. The determination of the ee is carried out by means of gas chromatography using a chiral column [Lipodex E (30m); 1300C isothermal; 190 KPa H2]. In the hydrogenation of EOV, [Rul2(p-cumene)]2 is used as metal complex and catalyst precursor. The determination of the ee is carried out after reaction with trifluoroacetic anhydride by means of gas chromatography using a chiral column [Lipodex E (30m)].In the hydrogenation of MEA, [Ir(COD)CI]2 is used as metal complex and catalyst precursor. The hydrogenation is carried out in bulk using 105 g of MEA (without solvent) in the presence of 70 mg of tetrabutylammonium iodide and 10 ml of acetic acid.

With hydrogen, bis(norbornadiene)rhodium(l)tetrafluoroborate, C62H78FeP4 in methanol, Time= 1h, T= 25 °C , p= 750.075Torr , Product distribution / selectivity Patent; SOLVIAS AG; WO2006/3195; (2006); (A1) English View in Reaxys B.1 :The method of carrying out the hydrogenations and the determination of the optical yields ee is described in general terms

by W. Weissensteiner et al in Organometallics 21 (2002), pages 1766-1774. The catalysts are in each case prepared in situ in the solvent by mixing of the ligand and metal complex as catalyst precursor (unless indicated otherwise = [Rh(norbornadiene)2]BF4). Unless indicated otherwise, the substrate concentration is 0.25 mol/l. The determination of conversion and ee of MAA is carried out by means of gas chromatography using a chiral column (Chirasil-L-val).The hydrogenations of EAC are carried out in ethanol in the presence of 5percent (v/v) of CF3CH2OH. The determination of the ee is carried out by means of gas chromatography using a chiral column [Lipodex E (30m); 1300C isothermal; 190 KPa H2]. In the hydrogenation of EOV, [Rul2(p-cumene)]2 is used as metal complex and catalyst precursor. The determination of the ee is carried out after reaction with trifluoroacetic anhydride by means of gas chromatography using a chiral column [Lipodex E (30m)].In the hydrogenation of MEA, [Ir(COD)CI]2 is used as metal complex and catalyst precursor. The hydrogenation is carried out in bulk using 105 g of MEA (without solvent) in the presence of 70 mg of tetrabutylammonium iodide and 10 ml of acetic acid.

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

With hydrogen, triethylamine, bis(norbornadiene)rhodium(l)tetrafluoroborate, C64H60FeN2P4 in tetrahydrofuran, Time= 1h, T= 25 °C , p= 3750.38Torr , Product distribution / selectivity Patent; SOLVIAS AG; WO2006/3195; (2006); (A1) English View in Reaxys With [Ru(CF3COO)2(1,5-COD)], (R,Rp)-2-[1-(dicyclohexylphosphinoethyl)]-1-[2-(diphenylphosphinomethyl)phenyl]ferrocene, hydrogen in methanol, Time= 2h, T= 25 °C , p= 15001.5Torr , enantioselective reaction Schuecker, Raffael; Mereiter, Kurt; Spindler, Felix; Weissensteiner, Walter; Advanced Synthesis and Catalysis; vol. 352; nb.

6; (2010); p. 1063 - 1074 View in Reaxys With hydrogen in tetrahydrofuran, Time= 16h, T= 20 °C , p= 5171.62Torr , Inert atmosphere, optical yield given as percent ee, enantioselective reaction Lee, Su Seong; Riduan, Siti Nurhanna; Erathodiyil, Nandanan; Lim, Jaehong; Cheong, Jian Liang; Cha, Junhoe; Han, Yu; Ying, Jackie Y.; Chemistry - A European Journal; vol. 18; nb. 24; (2012); p. 7394 - 7403 View in Reaxys With C56H36F12FeO10P2Ru4, hydrogen in ethanol, toluene, Time= 24h, T= 100 °C , p= 37503.8Torr , Autoclave, Reagent/catalyst, enantioselective reaction Moberg, Viktor; Duquesne, Robin; Roehrs, Oliver; Nachtigall, Jonny; Nordlander, Ebbe; Contaldi, Simone; Monari, Magda; Damoense, Llewellyn; Green, Michael; Hutton, Alan T.; Santelia, Daniela; Haukka, Matti; Chemistry--A European Journal; vol. 18; nb. 39; (2012); p. 12458 - 12478,21 View in Reaxys With C52H52FeO10P2Ru4, hydrogen in ethanol, toluene, Time= 24h, T= 100 °C , p= 37503.8Torr , Autoclave, enantioselective reaction Moberg, Viktor; Duquesne, Robin; Roehrs, Oliver; Nachtigall, Jonny; Nordlander, Ebbe; Contaldi, Simone; Monari, Magda; Damoense, Llewellyn; Green, Michael; Hutton, Alan T.; Santelia, Daniela; Haukka, Matti; Chemistry--A European Journal; vol. 18; nb. 39; (2012); p. 12458 - 12478,21 View in Reaxys With bis(norbornadiene)rhodium(l)tetrafluoroborate, (R)-1-{(RFc)-2-[2-(diphenylphosphino)phenyl]ferrocenyl}ethylbis[3,5-bis(trifluoromethyl)phenyl]phosphine, hydrogen in methanol, Time= 20h, T= 20 °C , p= 15201Torr , Autoclave, Reagent/catalyst Zirakzadeh, Afrooz; Gross, Manuela A.; Wang, Yaping; Mereiter, Kurt; Spindler, Felix; Weissensteiner, Walter; Organometallics; vol. 32; nb. 4; (2013); p. 1075 - 1084 View in Reaxys With di-μ-chlorobis(norbornadiene)dirhodium(I), (SFc)-2-((R)-1-diphenylphosphinoethyl)-(RFc)-2ηη-diphenylphosphino-1,1ηη-biferrocene, hydrogen in tetrahydrofuran, Time= 20h, T= 20 °C , p= 15201Torr , Autoclave, Catalytic behavior, Reagent/catalyst, Solvent Zirakzadeh, Afrooz; Gross, Manuela A.; Wang, Yaping; Mereiter, Kurt; Spindler, Felix; Weissensteiner, Walter; Organometallics; vol. 32; nb. 4; (2013); p. 1075 - 1084 View in Reaxys 3 : Example 3 Catalytic 6d Catalyzed Asymmetric Hydrogenation of α-Methyl Cinnamic Acid: In the glove box in an argon atmosphere,The catalyst 6d (3.6 mg) was added to a 5 mL hydrogenated vial and then the substrate η-methylcinnamic acid (32 mg, 0.2 mmol), triethylamine (22 mg, 0.2 mmol) and 1 mL of dichloromethane were added successively. The hydrogenated vials were placed in a hydrogenation reactor and the hydrogen was replaced three times and then filled with 30 atm H2 and reacted at room temperature for 4 h. After completion of the reaction, the reaction mixture was passed through a short silica gel column. 1HNMR was used to determine the conversion (81percent), and the enantioselective ee (81percent) of the reaction was determined by high performance liquid chromatography (HPLC).

With C49H66IrNOP(1+)*C32H12BF24 (1-), hydrogen, triethylamine in dichloromethane, Time= 4h, T= 20 °C , p= 22801.5Torr , Glovebox Patent; Wuhan Kaitelisi Technology Co., Ltd.; Zhang Xumu; Wang Qian; Dong Xiuqin; (12 pag.); CN106632478; (2017); (A) Chinese

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

View in Reaxys

O

H

HO

HO O

Rx-ID: 22694575 View in Reaxys 2/90 Yield 99 %

Conditions & References With hydrogen, triethylamine in methanol, Time= 0.5h, T= 20 °C , p= 4560.31Torr , optical yield given as percent ee, enantioselective reaction Li, Shen; Zhu, Shou-Fei; Zhang, Can-Ming; Song, Song; Zhou, Qi-Lin; Journal of the American Chemical Society; vol.

130; nb. 27; (2008); p. 8584 - 8585 View in Reaxys

99 %

With C38H36IrO2P, hydrogen, caesium carbonate in butan-1-ol, Time= 6h, T= 65 °C , p= 2280.15Torr , enantioselective reaction Yang, Shuang; Che, Wen; Wu, Hui-Ling; Zhu, Shou-Fei; Zhou, Qi-Lin; Chemical Science; vol. 8; nb. 3; (2017); p. 1977 1980 View in Reaxys

99 %

9 : Hydrogenation of α, α-unsaturated carboxylic acid The catalyst (S)-2d (3.7 mg, 0.005 mmol), η, η-unsaturated carboxylic acid 5 (0.5 mmol) was weighed in a glove box, Cesium carbonate (82 mg, 0.25 mmol) was sealed in a reaction tube equipped with a stirrer. After removal, add n-butanol with a syringe(2 mL), the inner tube was placed in a hydrogenation reactor and replaced by a pressurized-deflated operation (3-5 times) into a hydrogen atmosphere.The hydrogen pressure was 0.3 MPa and the stirring at 65 ° C was stopped. And then stop stirring, release hydrogen, the reaction system steamed After concentration, the system was adjusted to pH <3 with 3N aqueous hydrochloric acid solution and extracted with ether (10 mL x 3). The organic phases were combined and washed with saturated brineWashed, dried over anhydrous sodium sulfate. The desiccant was removed by suction filtration and distilled off to give the target product 6,1H NMR for its conversion.Reactions are fully converted. The ee values were analyzed by chiral HPLC after conversion of the product to the corresponding amide. The experimental results are shown in Table 8 With C38H36IrO2P, hydrogen, caesium carbonate in butan-1-ol, Time= 6h, T= 65 °C , p= 2250.23Torr , Glovebox, enantioselective reaction Patent; Nankai University; ZHOU, QILIN; ZHU, SHOUFEI; YANG, SHUANG; CHE, WEN; WANG, LIXIN; (15 pag.); CN106518931; (2017); (A) Chinese View in Reaxys

97 %

With C32H12BF24 (1-)*C54H71IrNP(1+), hydrogen, caesium carbonate in methanol, Time= 1h, T= 45 °C , p= 4560.31Torr , Autoclave, optical yield given as percent ee, enantioselective reaction Zhu, Shou-Fei; Yu, Yan-Bo; Li, Shen; Wang, Li-Xin; Zhou, Qi-Lin; Angewandte Chemie - International Edition; vol. 51; nb.

35; (2012); p. 8872 - 8875 View in Reaxys Reaction Steps: 2 1: (i) H2SO4, (ii) H2, Pd-C, EtOH 2: η-chymotrypsin, aq. NaOH With sodium hydroxide, η-chymotrypsin Cohen,S.G.; Milovanovic,A.; Journal of the American Chemical Society; vol. 90; (1968); p. 3495 - 3502 View in Reaxys

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

OH

O

O

H

HO

H

HO O

Rx-ID: 29577152 View in Reaxys 3/90 Yield

Conditions & References With [Rh((R,R)-Cy-SMS-Phos)(MeOH)2]BF4, hydrogen, N-cyclohexyl-cyclohexanamine in methanol, Time= 3h, T= 20 °C , p= 7500.75Torr , optical yield given as percent ee Zupancic, Borut; Mohar, Barbara; Stephan, Michel; Organic Letters; vol. 12; nb. 13; (2010); p. 3022 - 3025 View in Reaxys 5 :The chiral catalyst [Show Image] is used, the asymmetric catalytic hydrogenation of 2- benzyl acrylic acid 7 is carried out under the condition same to that of Embodiment 5, the result of the reaction is that: the conversion rate is 100percent, the yield is 93percent and the ee value of the product is 73percent.

Stage 1: With hydrogen, caesium carbonate, [(Sa-DTB-SIPHOX)Ir(COD)]BARF in methanol, Time= 12h, T= 20 °C , p= 4500.45Torr Stage 2: With hydrogenchloride in water, pH= < 3, Product distribution / selectivity Patent; Zhejiang Jiuzhou Pharmaceutical Co., Ltd.; EP2272853; (2011); (A1) English View in Reaxys With di(norbornadiene)rhodium(I) tetrafluoroborate, C33H48FeNP2, hydrogen in ethanol, Time= 5h, T= 20 °C , p= 760.051Torr , Resolution of racemate Patent; Wuhan Science and Technology Co., Ltd.; Zhang, Xumu; Chen, Caiyou; (17 pag.); CN105481909; (2016); (A) Chinese View in Reaxys With bis(norbornadiene)rhodium(l)tetrafluoroborate, C33H47FeNP2, hydrogen in ethanol, Time= 6h, T= 20 °C , p= 750.075Torr Chen, Caiyou; Wang, Heng; Zhang, Zhefan; Jin, Shicheng; Wen, Songwei; Ji, Jianjian; Chung, Lung Wa; Dong, XiuQin; Zhang, Xumu; Chemical Science; vol. 7; nb. 11; (2016); p. 6669 - 6673 View in Reaxys

O

H

HO

HO O

Rx-ID: 42532437 View in Reaxys 4/90 Yield 99 %

Conditions & References With C48H50Cl4N2O2P2Ru3, hydrogen, sodium hydrogencarbonate in methanol, Time= 24h, T= 20 °C , p= 3750.38Torr , Autoclave, enantioselective reaction Li, Jing; Shen, Jiefeng; Xia, Chao; Wang, Yanzhao; Liu, Delong; Zhang, Wanbin; Organic Letters; vol. 18; nb. 9; (2016); p.

2122 - 2125 View in Reaxys

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

OH

O

O

HO

H

H

HO

HO OH HO O

Rx-ID: 44747951 View in Reaxys 5/90 Yield

Conditions & References

48 %

With acetobacter aceti culture medium containing glucose, yeast extract, agar, glycerol and distilled wateracetobacter aceti, Time= 72h, Microbiological reaction Brenna, Elisabetta; Cannavale, Flavia; Crotti, Michele; De Vitis, Valerio; Gatti, Francesco G.; Migliazza, Gaia; Molinari, Francesco; Parmeggiani, Fabio; Romano, Diego; Santangelo, Sara; ChemCatChem; vol. 8; nb. 24; (2016); p. 3796 - 3803 View in Reaxys

O

H

O

HO O

Rx-ID: 2042019 View in Reaxys 6/90 Yield

Conditions & References With water, Time= 2h, lipase PS Colombo, M.; Amici, M. De; Micheli, C. De; Pitre, D.; Carrea, G.; Riva, S.; Tetrahedron: Asymmetry; vol. 2; nb. 10; (1991); p. 1021 - 1030 View in Reaxys Reaction Steps: 3 1: diisobutylaluminium hydride / tetrahydrofuran / 1 h / -70 °C / Inert atmosphere 2: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium bromide; sodium hypochlorite / dichloromethane / 0.42 h / -10 -5 °C / pH 9.5 3: aldehyde dehydrogenase from bovine lens; NAD / aq. phosphate buffer / 7 h / 30 °C / pH 8 / Enzymatic reaction With sodium hypochlorite, 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical, aldehyde dehydrogenase from bovine lens, NAD, diisobutylaluminium hydride, potassium bromide in tetrahydrofuran, aq. phosphate buffer, dichloromethane Knaus, Tanja; Mutti, Francesco G.; Humphreys, Luke D.; Turner, Nicholas J.; Scrutton, Nigel S.; Organic and Biomolecular Chemistry; vol. 13; nb. 1; (2015); p. 223 - 233 View in Reaxys

H

HO O

Rx-ID: 7672197 View in Reaxys 7/90 Yield 48 %

Conditions & References 4 :General procedure: 10 ml of dioxane is added to a 50 ml round-bottomed flask containing compound 6A (0.05 g, 1 eq), and 10 ml of 2N NaOH is slowly added thereto. After refluxing at 100 ° C for 2 hours, it was extracted with dichloromethane. To the extracted dichloromethane solution was added saturated ammonium chloride and extracted with dichloromethaneThe organic layer was dried with magnesium sulfate and then precipitated in about 200 ml of methanol cooled to -78 ° C. The precipitated solution was filtered and the filtered solid was washed with a mixed solution of methanol and distilled water in a volume ratio of 1: 1. The solid remaining in the filter was then taken to yield compound 4A.The water layer was acidified (pH 2-3) with hydrogen chloride and extracted with ethyl acetate. The organic layer extracted with ethylacetate was dried over magnesium sulfate

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and purified by column chromatography (eluent: ethyl acetate: n-hexane + 2: 8) to obtain compound 8A. Table 3 below shows the results of measurement of enantiomeric excess of Compound 8A using HPLC (eluent: 2-propanol: n-hexane = 5: 95).

With sodium hydroxide in 1,4-dioxane, water Solid phase= non-crosslinked chloromethylated polystyrene, Time= 2h, T= 100 °C Patent; Chonnam National Academic Foundation; Kim, Taek Hyun; Kang, Byung Sun; (19 pag.); KR2015/105875; (2015); (A) Korean View in Reaxys Valentine; Scott; Synthesis; (1978); p. 329,343 View in Reaxys 1 : EXAMPLE 1 After six additional recrystallizations from 50percent aqueous ethanol, there remained 18.8 g of the quinine salt.

The quinine salt (0.34 g) was treated with 100 ml of 1M sulfuric acid and extracted with chloroform (2*100 ml).

The combined organic extracts were dried over magnesium sulfate, filtered and concentrated.

The residue was purified by radial chromatography (5percent to 10percent methanol in chloroform, 2 mm plate) to yield 89 mg of (S)-2-methyl-3-phenylpropionic acid.

Patent; Merrell Dow Pharmaceuticals Inc.; US5047534; (1991); (A) English View in Reaxys Patent; Merrell Pharmaceuticals Inc.; US5840729; (1998); (A) English View in Reaxys

HO

H

HO O

Rx-ID: 39304043 View in Reaxys 8/90 Yield

Conditions & References Reaction Steps: 2 1: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium bromide; sodium hypochlorite / dichloromethane / 0.42 h / -10 -5 °C / pH 9.5 2: aldehyde dehydrogenase from bovine lens; NAD / aq. phosphate buffer / 7 h / 30 °C / pH 8 / Enzymatic reaction With sodium hypochlorite, 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical, aldehyde dehydrogenase from bovine lens, NAD, potassium bromide in aq. phosphate buffer, dichloromethane Knaus, Tanja; Mutti, Francesco G.; Humphreys, Luke D.; Turner, Nicholas J.; Scrutton, Nigel S.; Organic and Biomolecular Chemistry; vol. 13; nb. 1; (2015); p. 223 - 233 View in Reaxys

H

O

HO O

Rx-ID: 39304061 View in Reaxys 9/90 Yield 93 %

Conditions & References With aldehyde dehydrogenase from E.coli, ene-reductase from Saccharomyces cerevisiae, NADH in aq. phosphate buffer, Time= 6h, T= 30 °C , pH= 7, Enzymatic reaction, Time, chemoselective reaction Knaus, Tanja; Mutti, Francesco G.; Humphreys, Luke D.; Turner, Nicholas J.; Scrutton, Nigel S.; Organic and Biomolecular Chemistry; vol. 13; nb. 1; (2015); p. 223 - 233 View in Reaxys

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Reaction Steps: 3 1: ene-reductase from Saccharomyces cerevisiae; η-D-glucose; NADPH; glucose dehydrogenase / aq. phosphate buffer / 19 h / 30 °C / pH 7 / Enzymatic reaction 2: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium bromide; sodium hypochlorite / dichloromethane / 0.42 h / -10 -5 °C / pH 9.5 3: aldehyde dehydrogenase from bovine lens; NAD / aq. phosphate buffer / 7 h / 30 °C / pH 8 / Enzymatic reaction With glucose dehydrogenase, sodium hypochlorite, η-D-glucose, 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical, aldehyde dehydrogenase from bovine lens, ene-reductase from Saccharomyces cerevisiae, NAD, NADPH, potassium bromide in aq. phosphate buffer, dichloromethane Knaus, Tanja; Mutti, Francesco G.; Humphreys, Luke D.; Turner, Nicholas J.; Scrutton, Nigel S.; Organic and Biomolecular Chemistry; vol. 13; nb. 1; (2015); p. 223 - 233 View in Reaxys

O

H

HO

O

HO O

Rx-ID: 39304069 View in Reaxys 10/90 Yield

Conditions & References

5 %, 83 %

With aldehyde dehydrogenase from E.coli, ene-reductase from Saccharomyces cerevisiae, NADH in aq. phosphate buffer, Time= 1h, T= 30 °C , pH= 7, Enzymatic reaction, Time, chemoselective reaction Knaus, Tanja; Mutti, Francesco G.; Humphreys, Luke D.; Turner, Nicholas J.; Scrutton, Nigel S.; Organic and Biomolecular Chemistry; vol. 13; nb. 1; (2015); p. 223 - 233 View in Reaxys

O

H

HO O

Rx-ID: 39304175 View in Reaxys 11/90 Yield

Conditions & References With aldehyde dehydrogenase from bovine lens, NAD in aq. phosphate buffer, Time= 7h, T= 30 °C , pH= 8, Enzymatic reaction, Reagent/catalyst, pH-value, Solvent Knaus, Tanja; Mutti, Francesco G.; Humphreys, Luke D.; Turner, Nicholas J.; Scrutton, Nigel S.; Organic and Biomolecular Chemistry; vol. 13; nb. 1; (2015); p. 223 - 233 View in Reaxys

O

HO

O

OH

H

H

HO O

Rx-ID: 28260217 View in Reaxys 12/90 Yield

Conditions & References D.3 :0.41 g (2.53 mmol) of 2-methylcinnamic acid and 5 ml of degassed methanol are introduced in succession into a Schlenk vessel filled with argon. A catalyst solution consisting of 4.73 mg (0.01265 mmol) of [Rh(norbornadiene)2]BF4, 8.77 mg (0.0133 mmol) of ligand A and 5 ml of degassed methanol is prepared in a second Schlenk vessel filled with argon. This solution and the

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

catalyst solution are then transferred in succession by means of a steel capillary into a 50 ml autoclave filled with argon. The ratio of substrate/catalyst is 200. The autoclave is closed and a pressure of 5 bar is set by means of 4 flushing cycles (pressurization to 10 bar of hydrogen). The autoclave is thermostated at 25° C. and the reaction is started by switching on the stirrer. The reactor is stirred for 19 hours. After opening the autoclave, a reddish reaction solution is isolated. The conversion is quantitative (determined by means of GC and 1H-NMR). Removal of the solvent on a rotary evaporator gives a quantitative yield of 2-methyl-3-phenylpropionic acid having an enantiomeric purity of 29percent ee (determined by means of HPLC after conversion into the methyl ester; column: Chiracel OB.).

With hydrogen, (S)-1-diphenylphosphino-2-[η-(S)-hydroxy-(o-diphenylphosphinophenyl)methyl]ferrocene, [Rh(norbornadiene)2]BF4 in methanol, Time= 19h, T= 25 °C , p= 7500.75Torr , Product distribution / selectivity Patent; Lotz, Matthias; Spindler, Felix; US2008/287698; (2008); (A1) English View in Reaxys D.3 :A method similar to that of Example D3 is employed. 8.96 mg (0.0133 mmol) of methoxy-, TANIAPHOS are used in place of the ligand A. The conversion is 100percent. Removal of the solvent on a rotary evaporator gives a quantitative yield of 2methyl-3-phenylpropionic acid having an enantiomeric purity of 30percent ee.

With hydrogen, (S)-1-diphenylphosphino-2-[η-(S)-methoxy(o-diphenylphosphinophenyl)methyl]ferrocene, [Rh(norbornadiene)2]BF4 in methanol, Time= 19h, T= 25 °C , p= 7500.75Torr , Product distribution / selectivity Patent; Lotz, Matthias; Spindler, Felix; US2008/287698; (2008); (A1) English View in Reaxys With diphenyl{1-[(S)-2,6-bis-trimethylsilyl-3,5-dioxa-4-phospha-cyclohepta(2,1-a;3,4-a')dinaphthalen-4-yl]-3-methyl-2-indolyl}phosphine, bis(norbornadiene)rhodium(l)tetrafluoroborate, hydrogen in dichloromethane, Time= 20h, T= 20 °C , p= 7500.75Torr , Inert atmosphere, optical yield given as percent ee Wassenaar, Jeroen; Kuil, Mark; Reek, Joost N. H.; Advanced Synthesis and Catalysis; vol. 350; nb. 10; (2008); p. 1610 1614 View in Reaxys With bis(norbornadiene)rhodium(l)tetrafluoroborate, (S(p),S(p))-2,2''-bis(diphenylphosphino)-1,1''-biferrocene, hydrogen in methanol, Time= 15h, T= 25 °C , p= 3750.38Torr , Autoclave, optical yield given as percent ee, enantioselective reaction Espino, Gustavo; Xiao, Li; Puchberger, Michael; Mereiter, Kurt; Spindler, Felix; Manzano, Blanca R.; Jalon, Felix A.; Weissensteiner, Walter; Dalton Transactions; nb. 15; (2009); p. 2751 - 2763 View in Reaxys With 5% Pd(II)/C(eggshell), Cinchonidin in 1,4-dioxane, water, T= 22.84 °C , optical yield given as percent ee, enantioselective reaction Sugimura, Takashi; Ogawa, Hiroyuki; Chemistry Letters; vol. 39; nb. 3; (2010); p. 232 - 233 View in Reaxys With 5% Pd(II)/C(eggshell), Cinchonin in 1,4-dioxane, water, T= 22.84 °C , optical yield given as percent ee, enantioselective reaction Sugimura, Takashi; Ogawa, Hiroyuki; Chemistry Letters; vol. 39; nb. 3; (2010); p. 232 - 233 View in Reaxys With diisopropyl{1-[(S)-2,6-dimethyl-3,5-dioxa-4-phospha-cyclohepta(2,1-a;3,4-a')dinaphthalen-4-yl]-3-methyl-2-indolyl}phosphine, bis(norbornadiene)rhodium(l)tetrafluoroborate, hydrogen in dichloromethane, Time= 16h, T= 25 °C , p= 7500.75Torr , optical yield given as percent ee, enantioselective reaction Wassenaar, Jeroen; Kuil, Mark; Lutz, Martin; Spek, Anthony L.; Reek, Joost N. H.; Chemistry - A European Journal; vol.

16; nb. 22; (2010); p. 6509 - 6517 View in Reaxys 1.5 :Embodiment 1: Asymmetric catalytic hydrogenation of η- methyl cinnamic acid [Show Image] In the glove box, the catalyst (0.00125 mmol) and η- methyl cinnamic acid 1a (81 mg, 0.5 mmol) are weighted in the reaction inner tube with stirring bar, then the reaction inner tube is sealed for use. When the reaction inner tube is took out, the additive and the solvent are added, then the inner tube is placed into the hydrogenation reactor, the mixture is stirred under the hydrogen pressure of 0.6~10 Mpa till the pressure stops declining. Then the stirring is stopped, the hydrogen is released. After the system is condensed by evaporating off rotatably, the system is adjusted pH <3 with 3N hydrochloric acid water solution, extracted with diethyl ether (10 mL .x. 3), and

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separated, the organic phase is collected, washed with saturated salt water, and dried with anhydrous sodium sulfate. The desiccant is removed by suction filtration, the solvent is evaporated off by rotating, then the object product 2a is obtained. The conversion rate is analyzed through 1H NMR, after it is converted to amide, its ee value is analyzed through the chiral HPLC analysis.

The experimental results obtained are shown in Table 1: With hydrogen, C32H12BF24 (1-)*C43H42IrNOP(1+) in methanol, T= 20 °C , p= 4500.45Torr , Sealed tube, Product distribution / selectivity Patent; Zhejiang Jiuzhou Pharmaceutical Co., Ltd.; EP2275398; (2011); (A1) English View in Reaxys With bis(norbornadiene)rhodium(l)tetrafluoroborate, C53H50O5P2, hydrogen in dichloromethane, Time= 12h, T= 20 °C , p= 30003Torr , Inert atmosphere, optical yield given as percent ee, enantioselective reaction Robert, Tobias; Abiri, Zohar; Sandee, Albertus J.; Schmalz, Hans-Guenther; Reek, Joost N.H.; Tetrahedron Asymmetry; vol. 21; nb. 21-22; (2010); p. 2671 - 2674 View in Reaxys With bis(norbornadiene)rhodium(l)tetrafluoroborate, (3aR,8aR)-6-((3-(diphenylphosphanyl)[1,1'-biphenyl]-2-yl)oxy)-2,2-dimethyl-4,4,8,8-tetraphenyltetrahydro[1,3]dioxolo[4,5-e][1,3,2]dioxaphosphepine, hydrogen in dichloromethane, Time= 12h, T= 20 °C , p= 30003Torr , Inert atmosphere, optical yield given as percent ee, enantioselective reaction Robert, Tobias; Abiri, Zohar; Sandee, Albertus J.; Schmalz, Hans-Guenther; Reek, Joost N.H.; Tetrahedron Asymmetry; vol. 21; nb. 21-22; (2010); p. 2671 - 2674 View in Reaxys With 1% Pd/η-Al2O3, hydrogen, Time= 4h, T= 20 °C , p= 760.051Torr , enantioselective reaction Sun, Xiaojing; Williams, Christopher T.; Catalysis Communications; vol. 17; (2012); p. 13 - 17 View in Reaxys With (η4-1,5-cyclooctadiene)(1-[(4S)-(2-(1-adamantyl)-4,5-dihydrooxazolyl)ethyl]-3-(2,6-diisopropylphenyl)-4,5-dihydroimidazolin-2-ylidene)iridium(I) tetrakis(3,5-bis(trifluoromethyl)phenyl)borate, hydrogen in dichloromethane, Time= 16h, T= 25 °C , p= 37503.8Torr , Reagent/catalyst, enantioselective reaction Khumsubdee, Sakunchai; Fan, Yubo; Burgess, Kevin; Journal of Organic Chemistry; vol. 78; nb. 19; (2013); p. 9969 - 9974 View in Reaxys With 5% palladium on Al2O3, hydrogen, cinchonidine in N,N-dimethyl-formamide, Kinetics, Solvent, Reagent/catalyst, Optical yield = 17 percent ee; enantioselective reaction Sun, Xiaojing; Monnier, John R.; Williams, Christopher T.; Catalysis Letters; vol. 143; nb. 9; (2013); p. 881 - 886 View in Reaxys General procedure for hydrogenation General procedure: Hydrogenation was carried out in a magnetically stirred autoclave in 1,4-dioxane containing 2.5percent (v/v) of water under an atmospheric pressure of hydrogen at room temperature. The catalyst (20mg) was pre-treated in a H2 flow at 375°C for 30min. After cooling down and transferred to the autoclave, the catalyst was pre-treated with modifier CD (0.02mmol) in 4mL solvent for an additional 30min. Then, certain amount of substrate and BA, as an effective additive, in 2mL solvent were added to the mixture. After adjusting the hydrogen pressure to the desired H2 pressure, the stirring was started. For substrates 1–4, the mixture after reaction was first neutralized with a diluted HCl solution, extracted with ethyl ether and analyzed by hydrogen nuclear magnetic resonance (1H NMR, Bruker DRX 400MHz type spectrometer) for conversion and a high performance liquid chromatography (HPLC, 6890 Agilent Co.) equipped with a chiral column (Daicel Chiralcel OJ-H) for enantiomeric excess (ee). For substrates 5 and 6, the mixture after reaction was first neutralized with a diluted HCl solution. Then, the catalyst and liquid were separated by centrifugation. After passing the liquid phase through a short silica column and drying, the conversion and enantioselectivity of 5 or 6 were determined on a gas chromatograph (Agilent 6890, 30m×0.32mm×0.25μm HP19091G-B213 capillary column).

With cinchonidine, 5% Pd/CNT, hydrogen, benzylamine in 1,4-dioxane, water, p= 750.075Torr , Catalytic behavior, Reagent/ catalyst, enantioselective reaction Guan, Zaihong; Lu, Shengmei; Li, Can; Journal of Catalysis; vol. 311; (2014); p. 1 - 5 View in Reaxys 4.7.2. Condition B (for acid substrates).

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General procedure: For monodentate ligand study; Ir(COD)2BARF or Rh(COD)2BARF (3 molpercent) and appropriate monodentate ligand (6.6 molpercent) were dissolved in MeOH (0.5 M). The mixture was stirred for 15 min, then corresponding unsaturated acid (0.25 mmol) and Cs2CO3 (0.13 mmol) were added to the mixture. The resulting mixture was degassed by three cycles of freeze–pump–thaw and then transferred to a Parr bomb. The bomb was pressurized to 50 bar with hydrogen and the mixture was stirred at 300 rpm for 16 h. The bomb was then vented and solvent was evaporated. The crude product was passed through a short silica plug using 30 percent EtOAc/hexanes as the eluant. The enantiomeric ratio was then measured through chiral GC analysis.

With [Ir(cycloocta-1,5-diene)2](tetrakis(3,5-bis(trifluoromethyl)phenyl)borate), (1S,2S,4S,5R)-2-((1R)-(dinaphtho[2,1-d:1',2'-f] [1,3,2]dioxaphosphepin-4-yloxy)(6-methoxyquinolin-4-yl)methyl)-5-vinylquinuclidine, hydrogen, caesium carbonate in methanol, Time= 24h, T= 25 °C , p= 37503.8Torr , Reagent/catalyst, enantioselective reaction Khumsubdee, Sakunchai; Burgess, Kevin; Tetrahedron; vol. 70; nb. 6; (2014); p. 1326 - 1335 View in Reaxys With bis(norbornadiene)rhodium(l)tetrafluoroborate, (Sp)-2-{(R)-1-bis[3,5-bis(trifluoromethyl)phenyl]phosphinoethyl}-(Sp)-2ηdiphenylphosphino-1,1η-biferrocene, hydrogen in methanol, Time= 20h, T= 20 °C , p= 37503.8Torr , Inert atmosphere, Autoclave Zirakzadeh, Afrooz; Gross, Manuela A.; Wang, Yaping; Mereiter, Kurt; Weissensteiner, Walter; Organometallics; vol. 33; nb. 8; (2014); p. 1945 - 1952 View in Reaxys Stage 1: With bis(norbornadiene)rhodium(l)tetrafluoroborate, (R)-1-[2-(2'-diphenylphosphinophenyl)-ferrocenyl]ethyldi[bis-(3,5-trifluoromethyl)phenyl]phosphine, hydrogen in methanol, Time= 20h, T= 20 °C , p= 37503.8Torr , Inert atmosphere, Autoclave Stage 2: With hydrogen in methanol, Time= 16h, T= 20 °C , p= 15001.5Torr , Autoclave Zirakzadeh, Afrooz; Gross, Manuela A.; Wang, Yaping; Mereiter, Kurt; Weissensteiner, Walter; Organometallics; vol. 33; nb. 8; (2014); p. 1945 - 1952 View in Reaxys

O

OH

O

H

H

HO O

Rx-ID: 37944484 View in Reaxys 13/90 Yield

Conditions & References With aldehyde dehydrogenase from pseudomonas putida KT2440, ene reductase from gluconobacter oxydans, water, NADPH in aq. buffer, Time= 24h, T= 25 °C , pH= 6.2, Enzymatic reaction, Optical yield = 64 percent ee; enantioselective reaction Winkler, Till; Groeger, Harald; Hummel, Werner; ChemCatChem; vol. 6; nb. 4; (2014); p. 961 - 964 View in Reaxys

O

O

H

O

O

H

HO O

Rx-ID: 36848161 View in Reaxys 14/90 Yield 37 %, 27 %

Conditions & References Synthetic scale hydrolase-mediated hydrolysis of ethyl 2-methyl-3-phenylpropanoate 2a At first, Pseudomonas fluorescens (48.0mg) was added to ethyl 2-methyl-3-phenylpropanoate 2a (232.0mg, 1.21mmol) in a 0.1M phosphate buffer, pH 7 (20mL) and the reaction mixture was shaken at 750rpm at 24°C. An aliquot of the reaction mixture (1mL) was withdrawn at 20h. Following a mini work-up, chiral HPLC analysis was conducted. Conversion was estimated by an

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E-value calculator at 51percent.22 The reaction mixture was filtered at 20h through a pad of Celite® and the hydrolase was washed with water (2×20mL) and ethyl acetate (10×10mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×30mL) and then acidified with aqueous hydrochloric solution (10percent) and extracted with more (3×30mL) ethyl acetate. The combined organic layers were washed with brine (1×100mL) dried, filtered and concentrated under reduced pressure to produce a light yellow oil (186.8mg). Purification by column chromatography on silica gel using hexane/ethyl acetate 90/10 as the eluent gave the pure ester (R)-2a (63.7mg, 27percent) as a clear oil [η]20D=−36.4[η]D20=-36.4 (c 1.0, CHCl3), >98percent ee, lit.24 [η]20D=+28.4[η]D20=+28.4 (c 1.0, CHCl3), (S)-isomer, 82percent ee and the pure acid (S)-1a (76.6mg, 37percent) as a clear oil [η]20D=+28.0[η]D20=+28.0 (c 0.82, CHCl3), 96percent ee, lit.23 [η]20D=+30.2[η]D20=+30.2 (c 0.82, CHCl3), 99percent ee. 1H NMR spectra were identical to those for the racemic materials previously prepared.

With Pseudomonas fluorescens hydrolase in aq. phosphate buffer, Time= 20h, T= 24 °C , pH= 7, Resolution of racemate, Enzymatic reaction, Reagent/catalyst, Time, enantioselective reaction Deasy, Rebecca E.; Moody, Thomas S.; Maguire, Anita R.; Tetrahedron Asymmetry; vol. 24; nb. 23; (2013); p. 1480 - 1487 View in Reaxys

O

O

O

O

H

O

H

O

H

HO O

Rx-ID: 36848162 View in Reaxys 15/90 Yield

Conditions & References General procedure for the hydrolase-catalysed kinetic resolution of the 3-aryl alkanoic ethyl esters 2a–c (analytical scale) General procedure: A spatula tip of enzyme (η5–10mg, amount not critical) was added to the ester substrate 2a–c (η50mg) in a 0.1M phosphate buffer, pH 7 (4.5mL). The small test tubes were sealed and agitated at 700–750rpm and incubated for the appropriate length of time and temperature. The aqueous layer was extracted with diethyl ether (3×5mL) and the combined organic extracts were filtered through Celite® and concentrated under reduced pressure. The sample was analysed by 1H NMR spectroscopy, reconcentrated and dissolved in a mixture of isopropanol/hexane [10:90 (HPLC grade)]. The enantioselectivity was determined by chiral HPLC. The results of the screens are summarised in Tables 1 and 3.

With Pseudomonas fluorescens hydrolase in aq. phosphate buffer, Time= 10h, T= 20 °C , pH= 7, Resolution of racemate, Enzymatic reaction, Reagent/catalyst, enantioselective reaction Deasy, Rebecca E.; Moody, Thomas S.; Maguire, Anita R.; Tetrahedron Asymmetry; vol. 24; nb. 23; (2013); p. 1480 - 1487 View in Reaxys O

O

O

OH O

O

O

H

H

H

O

H

HO O

Rx-ID: 36848163 View in Reaxys 16/90

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Yield

Conditions & References General procedure for the hydrolase-catalysed kinetic resolution of the 3-aryl alkanoic ethyl esters 2a–c (analytical scale) General procedure: A spatula tip of enzyme (η5–10mg, amount not critical) was added to the ester substrate 2a–c (η50mg) in a 0.1M phosphate buffer, pH 7 (4.5mL). The small test tubes were sealed and agitated at 700–750rpm and incubated for the appropriate length of time and temperature. The aqueous layer was extracted with diethyl ether (3×5mL) and the combined organic extracts were filtered through Celite® and concentrated under reduced pressure. The sample was analysed by 1H NMR spectroscopy, reconcentrated and dissolved in a mixture of isopropanol/hexane [10:90 (HPLC grade)]. The enantioselectivity was determined by chiral HPLC. The results of the screens are summarised in Tables 1 and 3.

With Pseudomonas stutzeri hydrolase in aq. phosphate buffer, Time= 72h, T= 20 °C , pH= 7, Resolution of racemate, Enzymatic reaction, Reagent/catalyst, enantioselective reaction Deasy, Rebecca E.; Moody, Thomas S.; Maguire, Anita R.; Tetrahedron Asymmetry; vol. 24; nb. 23; (2013); p. 1480 - 1487 View in Reaxys

O O

H

HO

O

H

HO O

Rx-ID: 36848166 View in Reaxys 17/90 Yield

Conditions & References Reaction Steps: 2 1: sulfuric acid / Reflux 2: Pseudomonas fluorescens hydrolase / aq. phosphate buffer / 20 h / 24 °C / pH 7 / Resolution of racemate; Enzymatic reaction With sulfuric acid, Pseudomonas fluorescens hydrolase in aq. phosphate buffer Deasy, Rebecca E.; Moody, Thomas S.; Maguire, Anita R.; Tetrahedron Asymmetry; vol. 24; nb. 23; (2013); p. 1480 - 1487 View in Reaxys

O

O

O

O

H

HO

H

O

H

HO O

Rx-ID: 36848167 View in Reaxys 18/90 Yield

Conditions & References Reaction Steps: 2 1: sulfuric acid / Reflux 2: Pseudomonas fluorescens hydrolase / aq. phosphate buffer / 10 h / 20 °C / pH 7 / Resolution of racemate; Enzymatic reaction With sulfuric acid, Pseudomonas fluorescens hydrolase in aq. phosphate buffer Deasy, Rebecca E.; Moody, Thomas S.; Maguire, Anita R.; Tetrahedron Asymmetry; vol. 24; nb. 23; (2013); p. 1480 - 1487 View in Reaxys

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O

H

HO

HO O

Rx-ID: 3962088 View in Reaxys 19/90 Yield 51 % Spectr.

Conditions & References With hydrogen, (S,R)-<(P-N)RhNBD>ClO4 in ethanol, Time= 2.7h, T= 30 °C , study of the asymmetric hydrogenation of various prochiral substrates with chiral ligands containing rhodium(I) complexes of ferrocenylphosphonium as asymmetric catalysts, Product distribution Appelton, Trevor D.; Cullen, William R.; Evans, Sthephen; Kim, Tae-Jeong; Trotter, James; Journal of Organometallic Chemistry; vol. 279; (1985); p. 5 - 22 View in Reaxys

24 %Chromat.

With bis(norbornadiene)rhodium(l)tetrafluoroborate, hydrogen in tetrahydrofuran, Time= 24h, T= 20 °C , p= 7500.75Torr , optical yield given as percent ee, enantioselective reaction Lee, Jong-Dae; Thanh, Thien Co; Kim, Tae-Jeong; Sang, Ook Kang; Synlett; nb. 5; (2009); p. 771 - 774 View in Reaxys With [(D)*Ir(1,4-cyclooctadiene)]+[tetrakis(3,5-bis(trifluoromethyl)phenyl)borate]-, hydrogen in dichloromethane, Time= 15h, T= 20 °C , p= 37503.8Torr , Inert atmosphere, enantioselective reaction Li, Jia-Qi; Quan, Xu; Andersson, Pher G.; Chemistry - A European Journal; vol. 18; nb. 34; (2012); p. 10609 - 10616 View in Reaxys

H

O

N HO

OH

O

Rx-ID: 33275316 View in Reaxys 20/90 Yield 99 %

Conditions & References With tetra(n-butyl)ammonium hydroxide in water, tert-butyl alcohol, Time= 24h, T= 95 °C , Inert atmosphere, optical yield given as percent ee Morales, Marvin R.; Mellem, Kevin T.; Myers, Andrew G.; Angewandte Chemie - International Edition; vol. 51; nb. 19; (2012); p. 4568 - 4571 View in Reaxys

O

O O

OH

O

N

H

N

O O

OH

H

O HO O

Rx-ID: 29454100 View in Reaxys 21/90 Yield

Conditions & References With Candida antarctica lipase A wild type in acetonitrile, Time= 4h, T= 20 °C , aq. phosphate buffer, aq. buffer, Enzymatic reaction, optical yield given as percent ee, enantioselective reaction

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

Engstroem, Karin; Nyhlen, Jonas; Sandstroem, Anders G.; Baeckvall, Jan-E.; Journal of the American Chemical Society; vol. 132; nb. 20; (2010); p. 7038 - 7042 View in Reaxys With Candida antarctica lipase A Phe233Gly in acetonitrile, Time= 0.1h, T= 20 °C , aq. phosphate buffer, aq. buffer, Enzymatic reaction, optical yield given as percent ee, enantioselective reaction Engstroem, Karin; Nyhlen, Jonas; Sandstroem, Anders G.; Baeckvall, Jan-E.; Journal of the American Chemical Society; vol. 132; nb. 20; (2010); p. 7038 - 7042 View in Reaxys

H

N

N

O

S O

O

N

HN

S

O

HO

O

O

Rx-ID: 29894335 View in Reaxys 22/90 Yield

Conditions & References

95 %

With lithium hydroxide monohydrate, water in tetrahydrofuran, T= 0 - 20 °C , Inert atmosphere Fecourt, Fabien; Lopez, Gerald; Lee, Arie Van Der; Martinez, Jean; Dewynter, Georges; Tetrahedron Asymmetry; vol. 21; nb. 19; (2010); p. 2361 - 2366 View in Reaxys

N (v1)

Pol

N O

H

N

O (v1)

O

Pol

HN O O

HO O

Rx-ID: 28766712 View in Reaxys 23/90 Yield

Conditions & References With sodium hydroxide in 1,4-dioxane, Time= 4h Nguyen, Quynh Pham Bao; Kim, Jae Nyoung; Kim, Taek Hyeon; Tetrahedron Letters; vol. 50; nb. 28; (2009); p. 4015 - 4018 View in Reaxys

O

O

O

OH

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

O

O

O

O

OH

H

O

H

HO O

Rx-ID: 28960998 View in Reaxys 24/90 Yield

Conditions & References With 2-phenyl-3,4-dihydro-2H-benzo[4,5]thiazolo[3,2-a]pyrimidine, N-ethyl-N,N-diisopropylamine in toluene, Time= 24h, T= 0 °C , optical yield given as percent ee, enantioselective reaction Yang, Xing; Birman, Vladimir B.; Advanced Synthesis and Catalysis; vol. 351; nb. 14-15; (2009); p. 2301 - 2304 View in Reaxys

OH

O

O

O

I

NH O O

O

O

O

O O

O

N

N

H

HO O

HO

HO

Rx-ID: 26018123 View in Reaxys 25/90 Yield

Conditions & References Multistep reaction.

Green, Rachel; Merritt, Andrew T.; Bull, Steven D.; Chemical Communications; vol. 8; nb. 4; (2008); p. 508 - 510 View in Reaxys

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

H

O

O

HN

HO O

O

Rx-ID: 28260214 View in Reaxys 26/90 Yield

Conditions & References D.14 :The experimental procedure is similar to that of Example DI. 2.53 mmol of starting material are always used, and the ratio of substrate to catalyst (sic) is always 200. The reaction parameters and the results are summarized in Table I below.In Examples 5, 11, 16 and 20, toluene (10 ml) is used as solvent. In Examples 6 to 8, 12, 13, 17, 18, 21 and 22, ethanol (10 ml, in Examples 6 and 17 9.5 ml) is used as solvent. In Examples 9, 10, 14, 15 and 19, methanol (10 ml) is used as solvent.

With hydrogen, (S)-1-di(3,5-dimethyl-4-methoxyphenyl)phosphino-2-[η-(S)-hydroxy(o-di(3,5-bis(trifluoromethyl)phenyl)phosphinophenyl)methyl]ferrocene, [Rh(norbornadiene)2]BF4 in methanol, Time= 1h, T= 25 °C , p= 750.075Torr , Product distribution / selectivity Patent; Lotz, Matthias; Spindler, Felix; US2008/287698; (2008); (A1) English View in Reaxys

O

O

O

N H

HO O

Rx-ID: 10462651 View in Reaxys 27/90 Yield 78 %

Conditions & References With lithium hydroxide in tetrahydrofuran, T= 0 - 20 °C Suzuki, Takayoshi; Hisakawa, Shinya; Itoh, Yukihiro; Maruyama, Sakiko; Kurotaki, Mineko; Nakagawa, Hidehiko; Miyata, Naoki; Bioorganic and Medicinal Chemistry Letters; vol. 17; nb. 6; (2007); p. 1558 - 1561 View in Reaxys

O

Br

O

H

O HO O

Rx-ID: 11009424 View in Reaxys 28/90 Yield 90 mg

Conditions & References Multistep reaction.

McGhee, Andrea M.; Kizirian, Jean-Claude; Procter, David J.; Organic and Biomolecular Chemistry; vol. 5; nb. 7; (2007); p. 1021 - 1024 View in Reaxys

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

N

O

N

O

H

N

O

NH HO O

Rx-ID: 11198119 View in Reaxys 29/90 Yield

Conditions & References With sodium hydroxide in 1,4-dioxane, Time= 1h, Heating Le, Thanh Nguyen; Nguyen, Quynh Pham Bao; Kim, Jae Nyoung; Kim, Taek Hyeon; Tetrahedron Letters; vol. 48; nb. 44; (2007); p. 7834 - 7837 View in Reaxys

O

H

Cl HO O

Rx-ID: 11430404 View in Reaxys 30/90 Yield

Conditions & References Reaction Steps: 3 1.1: 36 percent / LiHMDS / tetrahydrofuran / 12 h / -78 - 20 °C 2.1: KHMDS / tetrahydrofuran; toluene / 1 h / -78 °C 2.2: 38 percent / tetrahydrofuran; toluene / -78 - -40 °C 3.1: 10 mg / aq. H2O2; LiOH / tetrahydrofuran / 16 h / 0 - 20 °C With lithium hydroxide, dihydrogen peroxide, potassium hexamethylsilazane, lithium hexamethyldisilazane in tetrahydrofuran, toluene Davies, Stephen G.; Garner, A. Christopher; Roberts, Paul M.; Smith, Andrew D.; Sweet, Miles J.; Thomson, James E.; Organic and Biomolecular Chemistry; vol. 4; nb. 14; (2006); p. 2753 - 2768 View in Reaxys Reaction Steps: 3 1.1: nBuLi / tetrahydrofuran / -78 °C 1.2: 83 percent / tetrahydrofuran / -78 °C 2.1: LDA / tetrahydrofuran / -78 °C 2.2: 63 percent / tetrahydrofuran / -78 - 20 °C 3.1: 78 percent / aq. LiOH / tetrahydrofuran / 0 - 20 °C With lithium hydroxide, n-butyllithium, lithium diisopropyl amide in tetrahydrofuran Suzuki, Takayoshi; Hisakawa, Shinya; Itoh, Yukihiro; Maruyama, Sakiko; Kurotaki, Mineko; Nakagawa, Hidehiko; Miyata, Naoki; Bioorganic and Medicinal Chemistry Letters; vol. 17; nb. 6; (2007); p. 1558 - 1561 View in Reaxys Reaction Steps: 4 1: 82 percent / Et3N / tetrahydrofuran / 1 h / 0 °C 2: 83 percent / Mg / diethyl ether / reflux, 4 h -> ambient temperature 3: LDA / tetrahydrofuran / -100 deg C, 2 h -> -50 deg C 4: 3 M aq. HCl / dioxane / 42 h / 90 - 95 °C With hydrogenchloride, magnesium, triethylamine, lithium diisopropyl amide in tetrahydrofuran, 1,4-dioxane, diethyl ether Guoqiang, Lin; Hjalmarsson, Mats; Hoegberg, Hans-Erik; Jernstedt, Karen; Norin, Torbjoern; Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry; vol. 38; nb. 9; (1984); p. 795 - 802

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

View in Reaxys Reaction Steps: 4 1: 82 percent / Et3N / tetrahydrofuran / 1 h / 0 °C 2: 83 percent / Mg / diethyl ether / reflux, 4 h -> ambient temperature 3: LDA / tetrahydrofuran / -100 deg C, 2 h -> -50 deg C 4: 76 percent / 3 M aq. HCl / dioxane / 42 h / 90 - 95 °C With hydrogenchloride, magnesium, triethylamine, lithium diisopropyl amide in tetrahydrofuran, 1,4-dioxane, diethyl ether Guoqiang, Lin; Hjalmarsson, Mats; Hoegberg, Hans-Erik; Jernstedt, Karen; Norin, Torbjoern; Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry; vol. 38; nb. 9; (1984); p. 795 - 802 View in Reaxys

H

O

N

O

HO O

O

Rx-ID: 11785690 View in Reaxys 31/90 Yield

Conditions & References Reaction Steps: 2 1.1: LDA / tetrahydrofuran / -78 °C 1.2: 63 percent / tetrahydrofuran / -78 - 20 °C 2.1: 78 percent / aq. LiOH / tetrahydrofuran / 0 - 20 °C With lithium hydroxide, lithium diisopropyl amide in tetrahydrofuran Suzuki, Takayoshi; Hisakawa, Shinya; Itoh, Yukihiro; Maruyama, Sakiko; Kurotaki, Mineko; Nakagawa, Hidehiko; Miyata, Naoki; Bioorganic and Medicinal Chemistry Letters; vol. 17; nb. 6; (2007); p. 1558 - 1561 View in Reaxys

O

N

OH

OH

H

Cl

O NH

H

H

OH HO O

Rx-ID: 10467878 View in Reaxys 32/90 Yield

Conditions & References With hydrogenchloride in 1,4-dioxane Andersson, Fredrik; Hedenstroem, Erik; Tetrahedron Asymmetry; vol. 17; nb. 13; (2006); p. 1952 - 1957 View in Reaxys

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

O O

O

HN N

H

O

O

HO O

Rx-ID: 11137429 View in Reaxys 33/90 Yield 11 mg, 10 mg

Conditions & References With lithium hydroxide, dihydrogen peroxide in tetrahydrofuran, Time= 16h, T= 0 - 20 °C Davies, Stephen G.; Garner, A. Christopher; Roberts, Paul M.; Smith, Andrew D.; Sweet, Miles J.; Thomson, James E.; Organic and Biomolecular Chemistry; vol. 4; nb. 14; (2006); p. 2753 - 2768 View in Reaxys

O H

O

N

NH

F O

F

HO

F

O

F

F

F

Rx-ID: 11214120 View in Reaxys 34/90 Yield 93 %, 97 %

Conditions & References Stage 1: With lithium aluminium tetrahydride in diethyl ether, Time= 0.5h, T= -10 °C Stage 2: With sodium chloride in diethyl ether, T= -10 - 20 °C Stage 3: With sodium chlorite, sodium dihydrogenphosphate, 2-methyl-but-2-ene in tetrahydrofuran, water, tert-butyl alcohol, Time= 1.2h, T= 20 °C , Further stages.

Tessier, Arnaud; Pytkowicz, Julien; Brigaud, Thierry; Angewandte Chemie - International Edition; vol. 45; nb. 22; (2006); p.

3677 - 3681 View in Reaxys

O

O

N

H

O

HO O

Rx-ID: 11400860 View in Reaxys 35/90 Yield

Conditions & References Reaction Steps: 2 1.1: KHMDS / tetrahydrofuran; toluene / 1 h / -78 °C 1.2: 38 percent / tetrahydrofuran; toluene / -78 - -40 °C 2.1: 10 mg / aq. H2O2; LiOH / tetrahydrofuran / 16 h / 0 - 20 °C With lithium hydroxide, dihydrogen peroxide, potassium hexamethylsilazane in tetrahydrofuran, toluene Davies, Stephen G.; Garner, A. Christopher; Roberts, Paul M.; Smith, Andrew D.; Sweet, Miles J.; Thomson, James E.; Organic and Biomolecular Chemistry; vol. 4; nb. 14; (2006); p. 2753 - 2768 View in Reaxys

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

OH

O

O

H

I

H

HO HO O

Rx-ID: 9901344 View in Reaxys 36/90 Yield

Conditions & References Multistep reaction. Title compound not separated from byproducts Kotake, Tomoya; Hayashi, Yoshio; Rajesh; Mukai, Yoshie; Takiguchi, Yuka; Kimura, Tooru; Kiso, Yoshiaki; Tetrahedron; vol. 61; nb. 15; (2005); p. 3819 - 3833 View in Reaxys

O

O

I

N N O O O

O

OH

O

H

H

HO O

Rx-ID: 9685552 View in Reaxys 37/90 Yield

Conditions & References Stage 1: With lithium diisopropyl amide in tetrahydrofuran, T= -78 - 0 °C Stage 2: With lithium hydroxide, dihydrogen peroxide in tetrahydrofuran, T= 0 °C , Further stages. Title compound not separated from byproducts.

Kotake, Tomoya; Rajesh; Hayashi, Yoshio; Mukai, Yoshie; Ueda, Mitsuhiro; Kimura, Tooru; Kiso, Yoshiaki; Tetrahedron Letters; vol. 45; nb. 18; (2004); p. 3651 - 3654 View in Reaxys

O

HO

O

O

OH

H

HO

H

HO O

Rx-ID: 10036551 View in Reaxys 38/90 Yield

Conditions & References With phosphate buffer, 2-bromohexanoic acid, Nocardia diaphanozonaria JCM 3208 whole cells in water, T= 30 °C , pH= 7.0, Title compound not separated from byproducts Kato, Dai-Ichiro; Miyamoto, Kenji; Ohta, Hiromichi; Tetrahedron Asymmetry; vol. 15; nb. 18; (2004); p. 2965 - 2973 View in Reaxys

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

OH

O

H

H

O O N

HO O

HO

Rx-ID: 9618144 View in Reaxys 39/90 Yield

Conditions & References With hydrogenchloride, acetic acid, Heating, Title compound not separated from byproducts Srivastava, Stuti; Goswami, Lalit N.; Dikshit, Dinesh K.; Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry; vol. 42; nb. 10; (2003); p. 2628 - 2631 View in Reaxys

H

O

N

O

HO O

Rx-ID: 9026989 View in Reaxys 40/90 Yield

Conditions & References

83 %

With lithium hydroxide in tetrahydrofuran, T= 0 °C Davies, Stephen G.; Dixon, Darren J.; Doisneau, Gilles J.-M.; Prodger, Jeremy C.; Sanganee, Hitesh J.; Tetrahedron Asymmetry; vol. 13; nb. 6; (2002); p. 647 - 658 View in Reaxys

O

OH

O O

H

N

H O HO O

Rx-ID: 8848295 View in Reaxys 41/90 Yield

Conditions & References With lithium hydroxide in tetrahydrofuran, Time= 25h, T= 0 - 24 °C , Title compound not separated from byproducts.

Alexander; Cook; Gibson; Kennedy; Journal of the Chemical Society. Perkin Transactions 1; nb. 13; (2001); p. 1538 - 1549 View in Reaxys

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

OH

O

H

O

H

N

O

O HO O

Rx-ID: 8849963 View in Reaxys 42/90 Yield

Conditions & References With lithium hydroxide in tetrahydrofuran, Time= 25h, T= 0 - 24 °C , Title compound not separated from byproducts.

Alexander; Cook; Gibson; Kennedy; Journal of the Chemical Society. Perkin Transactions 1; nb. 13; (2001); p. 1538 - 1549 View in Reaxys

O

OH

H

H

O N

O

O

HO O

Rx-ID: 8852653 View in Reaxys 43/90 Yield

Conditions & References With lithium hydroxide in tetrahydrofuran, Time= 25h, T= 0 - 24 °C , Title compound not separated from byproducts Alexander; Cook; Gibson; Kennedy; Journal of the Chemical Society. Perkin Transactions 1; nb. 13; (2001); p. 1538 - 1549 View in Reaxys

HO H

O

HO O

Rx-ID: 8912509 View in Reaxys 44/90 Yield 90 %

Conditions & References With ammonium cerium(IV) nitrate in water, acetonitrile, Time= 1h, T= 0 °C

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

Palomo, Claudio; Oiarbide, Mikel; Mielgo, Antonia; Gonzalez, Alberto; Garcia, Jesus M.; Landa, Cristina; Lecumberri, Ainara; Linden, Anthony; Organic Letters; vol. 3; nb. 21; (2001); p. 3249 - 3252 View in Reaxys

H

N-butyl-coniine I HO O

Rx-ID: 15266847 View in Reaxys 45/90 Yield

Conditions & References Reaction Steps: 4 1.1: LDA / tetrahydrofuran; hexane / 2 h / -78 °C 1.2: 80 percent / tetrahydrofuran; hexane / 1.5 h / -30 °C 2.1: LDA; DMPU / tetrahydrofuran; hexane / 4 h / -50 °C 2.2: tetrahydrofuran; hexane / 1 h / -30 °C 3.1: 85 percent / TBAF / tetrahydrofuran / 0.5 h / 20 °C 4.1: 90 percent / CAN / acetonitrile; H2O / 1 h / 0 °C With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone, ammonium cerium(IV) nitrate, tetrabutyl ammonium fluoride, lithium diisopropyl amide in tetrahydrofuran, hexane, water, acetonitrile Palomo, Claudio; Oiarbide, Mikel; Mielgo, Antonia; Gonzalez, Alberto; Garcia, Jesus M.; Landa, Cristina; Lecumberri, Ainara; Linden, Anthony; Organic Letters; vol. 3; nb. 21; (2001); p. 3249 - 3252 View in Reaxys

H

O O Si

HO O

Rx-ID: 15284474 View in Reaxys 46/90 Yield

Conditions & References Reaction Steps: 3 1.1: LDA; DMPU / tetrahydrofuran; hexane / 4 h / -50 °C 1.2: tetrahydrofuran; hexane / 1 h / -30 °C 2.1: 85 percent / TBAF / tetrahydrofuran / 0.5 h / 20 °C 3.1: 90 percent / CAN / acetonitrile; H2O / 1 h / 0 °C With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone, ammonium cerium(IV) nitrate, tetrabutyl ammonium fluoride, lithium diisopropyl amide in tetrahydrofuran, hexane, water, acetonitrile Palomo, Claudio; Oiarbide, Mikel; Mielgo, Antonia; Gonzalez, Alberto; Garcia, Jesus M.; Landa, Cristina; Lecumberri, Ainara; Linden, Anthony; Organic Letters; vol. 3; nb. 21; (2001); p. 3249 - 3252 View in Reaxys

Si

H

O

HO

O

O

Rx-ID: 15284627 View in Reaxys 47/90

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

Yield

Conditions & References Reaction Steps: 2 1: 85 percent / TBAF / tetrahydrofuran / 0.5 h / 20 °C 2: 90 percent / CAN / acetonitrile; H2O / 1 h / 0 °C With ammonium cerium(IV) nitrate, tetrabutyl ammonium fluoride in tetrahydrofuran, water, acetonitrile Palomo, Claudio; Oiarbide, Mikel; Mielgo, Antonia; Gonzalez, Alberto; Garcia, Jesus M.; Landa, Cristina; Lecumberri, Ainara; Linden, Anthony; Organic Letters; vol. 3; nb. 21; (2001); p. 3249 - 3252 View in Reaxys

OH

O O

H

H

O HN

HO O

O

Rx-ID: 8649941 View in Reaxys 48/90 Yield

Conditions & References With methanol, potassium hydroxide, Heating, Hydrolysis, Title compound not separated from byproducts Chandrasekhar, Sosale; Kausar, Amina; Tetrahedron Asymmetry; vol. 11; nb. 11; (2000); p. 2249 - 2253 View in Reaxys

H

O N HO O

Rx-ID: 15735868 View in Reaxys 49/90 Yield

Conditions & References Reaction Steps: 3 1.1: LDA / tetrahydrofuran / -78 °C 1.2: 95 percent / tetrahydrofuran 2.1: 24 h / Heating 3.1: KOH; MeOH / Heating With methanol, potassium hydroxide, lithium diisopropyl amide in tetrahydrofuran, 1.1: Metallation / 1.2: Alkylation / 2.1: Ring cleavage / 3.1: Hydrolysis Chandrasekhar, Sosale; Kausar, Amina; Tetrahedron Asymmetry; vol. 11; nb. 11; (2000); p. 2249 - 2253 View in Reaxys

H

O N HO O

Rx-ID: 15740936 View in Reaxys 50/90 Yield

Conditions & References Reaction Steps: 2 1: 24 h / Heating 2: KOH; MeOH / Heating With methanol, potassium hydroxide, 1: Ring cleavage / 2: Hydrolysis

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

Chandrasekhar, Sosale; Kausar, Amina; Tetrahedron Asymmetry; vol. 11; nb. 11; (2000); p. 2249 - 2253 View in Reaxys

O

HN

H

O

N

O

O HO O

O

Rx-ID: 5118676 View in Reaxys 51/90 Yield

Conditions & References

96 %, 98 %

With lithium hydroxide, water in tetrahydrofuran, Time= 24h, Ambient temperature Bull, Steven D.; Davies, Stephen G.; Jones, Simon; Sanganee, Hitesh J.; Journal of the Chemical Society - Perkin Transactions 1; nb. 4; (1999); p. 387 - 398 View in Reaxys

O

OH

O O

H

N

H O

O HN HO O

O

Rx-ID: 5041597 View in Reaxys 52/90 Yield

Conditions & References

94 %

With lithium hydroxide, Yield given Gibson, Colin L.; Gillon, Karen; Cook, Stuart; Tetrahedron Letters; vol. 39; nb. 37; (1998); p. 6733 - 6736 View in Reaxys

O

OH

O O

H

N

H O

O HN HO O

O

Rx-ID: 5041598 View in Reaxys 53/90

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

Yield

Conditions & References

95 %

With lithium hydroxide, Yield given Gibson, Colin L.; Gillon, Karen; Cook, Stuart; Tetrahedron Letters; vol. 39; nb. 37; (1998); p. 6733 - 6736 View in Reaxys

O

OH

OH H

N

H

O HO O

Rx-ID: 4016116 View in Reaxys 54/90 Yield

Conditions & References With tetra(n-butyl)ammonium hydroxide in water, tert-butyl alcohol, Heating, Title compound not separated from byproducts Myers, Andrew G.; Yang, Bryant H.; Chen, Hou; Gleason, James L.; Journal of the American Chemical Society; vol. 116; nb. 20; (1994); p. 9361 - 9362 View in Reaxys With tetra(n-butyl)ammonium hydroxide in tert-butyl alcohol, Heating, Yield given. Yields of byproduct given. Title compound not separated from byproducts Myers, Andrew G.; Yang, Bryant H.; Chen, Hou; McKinstry, Lydia; Kopecky, David J.; Gleason, James L.; Journal of the American Chemical Society; vol. 119; nb. 28; (1997); p. 6496 - 6511 View in Reaxys

O

H

N HO

O

O

O

Rx-ID: 4699524 View in Reaxys 55/90 Yield

Conditions & References With lithium hydroxide, dihydrogen peroxide in tetrahydrofuran, T= 0 °C Ghosh, Arun K.; Cho, Hanna; Onishi, Masanobu; Tetrahedron Asymmetry; vol. 8; nb. 6; (1997); p. 821 - 824 View in Reaxys

O

H

Cl

HO HO O

Rx-ID: 4807950 View in Reaxys 56/90 Yield

Conditions & References With hydrogen, 10 wt. % palladium on activated carbon in methanol, Time= 12h, Ambient temperature, Yield given Ferorelli; Loiodice; Tortorella; Amoroso; Bettoni; Conte- Camerino; De Luca; Farmaco; vol. 52; nb. 6-7; (1997); p. 367 374 View in Reaxys

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

O

H

N

HO

H

H

HO O

Rx-ID: 17169384 View in Reaxys 57/90 Yield

Conditions & References Reaction Steps: 2 1: 95 percent / LiCl, diisopropylamine, n-BuLi / tetrahydrofuran; hexane / -78 °C 2: aq. n-Bu4NOH / 2-methyl-propan-2-ol / Heating With n-butyllithium, tetra(n-butyl)ammonium hydroxide, diisopropylamine, lithium chloride in tetrahydrofuran, hexane, tert-butyl alcohol Myers, Andrew G.; Yang, Bryant H.; Chen, Hou; McKinstry, Lydia; Kopecky, David J.; Gleason, James L.; Journal of the American Chemical Society; vol. 119; nb. 28; (1997); p. 6496 - 6511 View in Reaxys Reaction Steps: 2 1: 1.) LDA, LiCl / 1.) THF, from -78 to 23 deg C, 80 min, 2.) THF, -78 deg C, 8 h 2: tetra-n-butylammonium hydroxide / H2O; 2-methyl-propan-2-ol / Heating With tetra(n-butyl)ammonium hydroxide, lithium chloride, lithium diisopropyl amide in water, tert-butyl alcohol Myers, Andrew G.; Yang, Bryant H.; Chen, Hou; Gleason, James L.; Journal of the American Chemical Society; vol. 116; nb. 20; (1994); p. 9361 - 9362 View in Reaxys

O

H

1.2.2.3-tetramethyl-cyclopentylcarbinol Cl HO O

Rx-ID: 17172143 View in Reaxys 58/90 Yield

Conditions & References Reaction Steps: 3 1: 83 percent / Et3N / tetrahydrofuran / 0.17 h 2: 95 percent / LiCl, diisopropylamine, n-BuLi / tetrahydrofuran; hexane / -78 °C 3: aq. n-Bu4NOH / 2-methyl-propan-2-ol / Heating With n-butyllithium, tetra(n-butyl)ammonium hydroxide, triethylamine, diisopropylamine, lithium chloride in tetrahydrofuran, hexane, tert-butyl alcohol Myers, Andrew G.; Yang, Bryant H.; Chen, Hou; McKinstry, Lydia; Kopecky, David J.; Gleason, James L.; Journal of the American Chemical Society; vol. 119; nb. 28; (1997); p. 6496 - 6511 View in Reaxys

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

O

H

N O

HO O

O

Rx-ID: 4201083 View in Reaxys 59/90 Yield

Conditions & References

100 %

With lithium hydroxide, water in tetrahydrofuran, T= 0 - 25 °C Davies, Stephen G.; Sanganee, Hitesh J.; Tetrahedron: Asymmetry; vol. 6; nb. 3; (1995); p. 671 - 674 View in Reaxys

O

OH

H

H

O

N

HO O

O

Rx-ID: 4289289 View in Reaxys 60/90 Yield

Conditions & References With sulfuric acid in acetic acid, Time= 4h, Heating, Yield given. Yields of byproduct given. Title compound not separated from byproducts Kanemasa; Ueno; Onimura; Kikukawa; Yamamoto; Tetrahedron; vol. 51; nb. 38; (1995); p. 10453 - 10462 View in Reaxys

O

H

N O HO

O

O

Rx-ID: 4369811 View in Reaxys 61/90 Yield

Conditions & References With lithium hydroperoxide in tetrahydrofuran, water, T= 0 °C Sibi; Sibi, Mukund P.; Deshpande; Deshpande, Prasad K.; Ji; Jianguo, Ji; Tetrahedron Letters; vol. 36; nb. 49; (1995); p.

8965 - 8968 View in Reaxys

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

H

C O

Br

HO O

Rx-ID: 17971757 View in Reaxys 62/90 Yield

Conditions & References Reaction Steps: 2 1: 81 percent / NaHMDS / tetrahydrofuran / -78 to 0 deg C 2: LiO2H / tetrahydrofuran; H2O / 0 °C With lithium hydroperoxide, sodium hexamethyldisilazane in tetrahydrofuran, water Sibi; Sibi, Mukund P.; Deshpande; Deshpande, Prasad K.; Ji; Jianguo, Ji; Tetrahedron Letters; vol. 36; nb. 49; (1995); p.

8965 - 8968 View in Reaxys

OH

O

HO

O H

O

H

NH

Br

O

N HO O

Rx-ID: 2400803 View in Reaxys 63/90 Yield

Conditions & References With lithium hydroxide, lithium diisopropyl amide, 1.) THF, 0 deg C, Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts Davies; Doisneau; Prodger; Sanganee; Tetrahedron Letters; vol. 35; nb. 15; (1994); p. 2373 - 2376 View in Reaxys

O

HN H

O

N O

N

HO

O

O

O

N H

Rx-ID: 2510307 View in Reaxys 64/90 Yield

Conditions & References With lithium hydroxide, dihydrogen peroxide, methyl chloroformate, 1.) THF, 30 min, 2.) THF, RT, 4 h, Yield given. Multistep reaction. Yields of byproduct given Chu, Kent S.; Negrete, George R.; Konopebki, Joseph P.; Lakner, Frederick J.; Woo, Nam-Tae; Olmstead, Marilyn M.; Journal of the American Chemical Society; vol. 114; nb. 5; (1992); p. 1800 - 1812 View in Reaxys

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

O

O

H

N HO O

N

O

O

Rx-ID: 2513753 View in Reaxys 65/90 Yield 77 %

Conditions & References With lithium hydroxide, dihydrogen peroxide in tetrahydrofuran, Time= 0.333333h Chu, Kent S.; Negrete, George R.; Konopebki, Joseph P.; Lakner, Frederick J.; Woo, Nam-Tae; Olmstead, Marilyn M.; Journal of the American Chemical Society; vol. 114; nb. 5; (1992); p. 1800 - 1812 View in Reaxys Reaction Steps: 2 1: aq. NaOH / methanol / 0.67 h / 4 °C 2: 1.) 30percent aq. H2O2, aq. LiOH, 2.) methyl chloroformate / 1.) THF, 30 min, 2.) THF, RT, 4 h With lithium hydroxide, sodium hydroxide, dihydrogen peroxide, methyl chloroformate in methanol Chu, Kent S.; Negrete, George R.; Konopebki, Joseph P.; Lakner, Frederick J.; Woo, Nam-Tae; Olmstead, Marilyn M.; Journal of the American Chemical Society; vol. 114; nb. 5; (1992); p. 1800 - 1812 View in Reaxys Reaction Steps: 2 1: aq. NaOH / methanol / 0.67 h / 4 °C 2: 1.) 30percent aq. H2O2, aq. LiOH / 1.) THF, 30 min, 2.) THF, RT, 4 h With lithium hydroxide, sodium hydroxide, dihydrogen peroxide in methanol Chu, Kent S.; Negrete, George R.; Konopebki, Joseph P.; Lakner, Frederick J.; Woo, Nam-Tae; Olmstead, Marilyn M.; Journal of the American Chemical Society; vol. 114; nb. 5; (1992); p. 1800 - 1812 View in Reaxys Reaction Steps: 2 1: 80percent methanolic KOH / 0.33 h / 0 °C 2: LiOOH With potassium hydroxide, lithium hydroperoxide Negrete, George R.; Konopelski, Joseph P.; Tetrahedron: Asymmetry; vol. 2; nb. 2; (1991); p. 105 - 108 View in Reaxys

O O

O

N

H

N

O O

OH

O HO O

Rx-ID: 3108372 View in Reaxys 66/90 Yield

Conditions & References With phosphate buffer, water in acetonitrile, T= 25 °C , η-chymotrypsin as catalyst, pH: 7.5; stereospecifity in hydrolysis of acylated η-chymotrypsins, Rate constant, Mechanism Oetvoes, Laszlo; Kraicsovits, Ferenc; Tetrahedron; vol. 48; nb. 23; (1992); p. 5009 - 5014

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

View in Reaxys

O H

O

HO O

Rx-ID: 3231137 View in Reaxys 67/90 Yield

Conditions & References

89 %

With water, Wilkinson's catalyst in ethanol, Time= 5h, Heating Oppolzer, Wolfgang; Lienard, Philippe; Helvetica Chimica Acta; vol. 75; nb. 8; (1992); p. 2572 - 2582 View in Reaxys

O

Cl

HN

O H

O

N

O O

N

HO

O

O

O

N H

Rx-ID: 3356190 View in Reaxys 68/90 Yield

Conditions & References With lithium hydroxide, dihydrogen peroxide, 1.) THF, 30 min, 2.) THF, RT, 4 h, Yield given. Multistep reaction. Yields of byproduct given Chu, Kent S.; Negrete, George R.; Konopebki, Joseph P.; Lakner, Frederick J.; Woo, Nam-Tae; Olmstead, Marilyn M.; Journal of the American Chemical Society; vol. 114; nb. 5; (1992); p. 1800 - 1812 View in Reaxys

O O O

S N

H

HO O

Rx-ID: 19572904 View in Reaxys 69/90 Yield

Conditions & References Reaction Steps: 2 1: 86 percent / Ti(i-PrO)4, molecular sieves / 3 h / 150 °C 2: 89 percent / H2O / <RhCl(PPh3)3> / ethanol / 5 h / Heating With titanium(IV) isopropylate, molecular sieve, water, Wilkinson's catalyst in ethanol Oppolzer, Wolfgang; Lienard, Philippe; Helvetica Chimica Acta; vol. 75; nb. 8; (1992); p. 2572 - 2582 View in Reaxys

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

H

Br HO O

Rx-ID: 20993453 View in Reaxys 70/90 Yield

Conditions & References Reaction Steps: 2 1: 1.) hexamethyldisilylamide / 1.) THF, -78 deg C, 2.5 h, 2.) THF, -23 deg C, 4 h 2: 77 percent / 30percent aq. H2O2, aq. LiOH / tetrahydrofuran / 0.33 h With lithium hydroxide, dihydrogen peroxide, HMDS in tetrahydrofuran Chu, Kent S.; Negrete, George R.; Konopebki, Joseph P.; Lakner, Frederick J.; Woo, Nam-Tae; Olmstead, Marilyn M.; Journal of the American Chemical Society; vol. 114; nb. 5; (1992); p. 1800 - 1812 View in Reaxys Reaction Steps: 3 1: 1.) hexamethyldisilylamide / 1.) THF, -78 deg C, 2.5 h, 2.) THF, -23 deg C, 4 h 2: aq. NaOH / methanol / 0.67 h / 4 °C 3: 1.) 30percent aq. H2O2, aq. LiOH, 2.) methyl chloroformate / 1.) THF, 30 min, 2.) THF, RT, 4 h With lithium hydroxide, sodium hydroxide, dihydrogen peroxide, HMDS, methyl chloroformate in methanol Chu, Kent S.; Negrete, George R.; Konopebki, Joseph P.; Lakner, Frederick J.; Woo, Nam-Tae; Olmstead, Marilyn M.; Journal of the American Chemical Society; vol. 114; nb. 5; (1992); p. 1800 - 1812 View in Reaxys Reaction Steps: 3 1: 1.) hexamethyldisilylamide / 1.) THF, -78 deg C, 2.5 h, 2.) THF, -23 deg C, 4 h 2: aq. NaOH / methanol / 0.67 h / 4 °C 3: 1.) 30percent aq. H2O2, aq. LiOH / 1.) THF, 30 min, 2.) THF, RT, 4 h With lithium hydroxide, sodium hydroxide, dihydrogen peroxide, HMDS in methanol Chu, Kent S.; Negrete, George R.; Konopebki, Joseph P.; Lakner, Frederick J.; Woo, Nam-Tae; Olmstead, Marilyn M.; Journal of the American Chemical Society; vol. 114; nb. 5; (1992); p. 1800 - 1812 View in Reaxys

O

H

HO

HO O

Rx-ID: 438148 View in Reaxys 71/90 Yield

Conditions & References With L-menthylamine Pickard; Yates; Journal of the Chemical Society; vol. 95; (1909); p. 1018 View in Reaxys With Quinine Kipping; Hunter; Journal of the Chemical Society; vol. 83; (1903); p. 1007 View in Reaxys Cram,D.J.; Wingrove,A.S.; Journal of the American Chemical Society; vol. 86; (1964); p. 5490 - 5496 View in Reaxys Watson,M.B.; Youngson,G.W.; Journal of the Chemical Society [Section] C: Organic; (1968); p. 258 - 262 View in Reaxys

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

Reaction Steps: 2 1: HCl / 24 h / Ambient temperature 2: water / 2 h / lipase PS With hydrogenchloride, water Colombo, M.; Amici, M. De; Micheli, C. De; Pitre, D.; Carrea, G.; Riva, S.; Tetrahedron: Asymmetry; vol. 2; nb. 10; (1991); p. 1021 - 1030 View in Reaxys

OH

O

H

O

OH HO O

Rx-ID: 1364727 View in Reaxys 72/90 Yield

Conditions & References (decarboxylation) Terashima,S. et al.; Chemical and Pharmaceutical Bulletin; vol. 18; (1970); p. 1124 - 1136 View in Reaxys Reaction Steps: 3 1: dimethylformamide / 4 h / 100 - 110 °C 2: HCl / 24 h / Ambient temperature 3: water / 2 h / lipase PS With hydrogenchloride, water in N,N-dimethyl-formamide Colombo, M.; Amici, M. De; Micheli, C. De; Pitre, D.; Carrea, G.; Riva, S.; Tetrahedron: Asymmetry; vol. 2; nb. 10; (1991); p. 1021 - 1030 View in Reaxys

O

H

H

HO O

Rx-ID: 2147536 View in Reaxys 73/90 Yield 90 %

Conditions & References With water, chromic acid in diethyl ether, Time= 2h, T <25 deg C Rangaishenvi, Milind V.; Singaram, Bakthan; Brown, Herbert C.; Journal of Organic Chemistry; vol. 56; nb. 10; (1991); p.

3286 - 3294 View in Reaxys

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

O

H

HN

O

O

N H

N

HO O

N H

Rx-ID: 2510306 View in Reaxys 74/90 Yield

Conditions & References With lithium hydroperoxide Negrete, George R.; Konopelski, Joseph P.; Tetrahedron: Asymmetry; vol. 2; nb. 2; (1991); p. 105 - 108 View in Reaxys

O

OH

OH O

O

H

H HO

O HO O

Rx-ID: 2792917 View in Reaxys 75/90 Yield

Conditions & References Yield given. Multistep reaction. Yields of byproduct given Yu; Simon; Tetrahedron; vol. 47; nb. 43; (1991); p. 9035 - 9052 View in Reaxys

H

Cl HO O

Rx-ID: 21039732 View in Reaxys 76/90 Yield

Conditions & References Reaction Steps: 5 1: 1.) NaH / 1.) ethyl ether, reflux, 2.) ethyl ether, RT, 6 h 2: aq. KOH / ethanol / 24 h / Heating 3: dimethylformamide / 4 h / 100 - 110 °C 4: HCl / 24 h / Ambient temperature 5: water / 2 h / lipase PS With hydrogenchloride, potassium hydroxide, water, sodium hydride in ethanol, N,N-dimethyl-formamide Colombo, M.; Amici, M. De; Micheli, C. De; Pitre, D.; Carrea, G.; Riva, S.; Tetrahedron: Asymmetry; vol. 2; nb. 10; (1991); p. 1021 - 1030 View in Reaxys

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

O

H

O O O HO O

Rx-ID: 21064054 View in Reaxys 77/90 Yield

Conditions & References Reaction Steps: 4 1: aq. KOH / ethanol / 24 h / Heating 2: dimethylformamide / 4 h / 100 - 110 °C 3: HCl / 24 h / Ambient temperature 4: water / 2 h / lipase PS With hydrogenchloride, potassium hydroxide, water in ethanol, N,N-dimethyl-formamide Colombo, M.; Amici, M. De; Micheli, C. De; Pitre, D.; Carrea, G.; Riva, S.; Tetrahedron: Asymmetry; vol. 2; nb. 10; (1991); p. 1021 - 1030 View in Reaxys

O H

B O HO O

Rx-ID: 21089128 View in Reaxys 78/90 Yield

Conditions & References Reaction Steps: 2 2: 90 percent / chromic acid, water / diethyl ether / 2 h / T <25 deg C With water, chromic acid in diethyl ether Rangaishenvi, Milind V.; Singaram, Bakthan; Brown, Herbert C.; Journal of Organic Chemistry; vol. 56; nb. 10; (1991); p.

3286 - 3294 View in Reaxys

O

O

O

H

O

H

HO O

Rx-ID: 2042020 View in Reaxys 79/90 Yield 50 %, 44 %

Conditions & References With lipase from Pseudomonas sp. (Amano), Time= 3h, Ambient temperature, 0.1 phosphate buffer, pH 7.0 Delnick, Deborah L.; Margolin, Alexey L.; Tetrahedron Letters; vol. 31; nb. 47; (1990); p. 6797 - 6798 View in Reaxys

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

O O O

S

O O

N

S

H

NH

HO O

Rx-ID: 2474734 View in Reaxys 80/90 Yield

Conditions & References

81 %

With lithium hydroxide, dihydrogen peroxide in tetrahydrofuran, water, T= 0 °C Oppolzer, Wolfgang; Rodriguez, Ines; Starkemann, Christian; Walther, Eric; Tetrahedron Letters; vol. 31; nb. 35; (1990); p. 5019 - 5022 View in Reaxys

H NH

H

O S

N

O O

S

HO

O

O

O

Rx-ID: 2691104 View in Reaxys 81/90 Yield

Conditions & References With lithium hydroxide, dihydrogen peroxide in tetrahydrofuran, water, 1.) 0 deg C, 1 h; 2.) room temp., 16 h Oppolzer, Wolfgang; Moretti, Robert; Thomi, Silvia; Tetrahedron Letters; vol. 30; nb. 41; (1989); p. 5603 - 5606 View in Reaxys

H

O

N

HO O

O

O

O

O

Rx-ID: 2700540 View in Reaxys 82/90 Yield 90 %

Conditions & References With hydrogenchloride, Time= 3h, Heating Kawanami, Yasuhiro; Ito, Yoshio; Kitagawa, Toshiyuki; Taniguchi, Yoshiyuki; Katsuki, Tsutomu; Yamaguchi, Masaru; Tetrahedron Letters; vol. 25; nb. 8; (1984); p. 857 - 860 View in Reaxys

O

OH

O H

H

I

N OH

HO O

Rx-ID: 3385499 View in Reaxys 83/90

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

Yield

Conditions & References With hydrogenchloride, lithium diisopropyl amide, 1.) THF, 0 deg C, 2 h, 2.) dioxane, 90-95 deg C, 42 h, Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts Guoqiang, Lin; Hjalmarsson, Mats; Hoegberg, Hans-Erik; Jernstedt, Karen; Norin, Torbjoern; Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry; vol. 38; nb. 9; (1984); p. 795 - 802 View in Reaxys

OH

O

H

H

O

N

HO O

HO

Rx-ID: 3499086 View in Reaxys 84/90 Yield

Conditions & References With hydrogenchloride in 1,4-dioxane, Time= 42h, T= 90 - 95 °C , Yield given. Yields of byproduct given. Title compound not separated from byproducts Guoqiang, Lin; Hjalmarsson, Mats; Hoegberg, Hans-Erik; Jernstedt, Karen; Norin, Torbjoern; Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry; vol. 38; nb. 9; (1984); p. 795 - 802 View in Reaxys

H

O

N

HO O

HO

Rx-ID: 3499087 View in Reaxys 85/90 Yield

Conditions & References

76 %

With hydrogenchloride in 1,4-dioxane, Time= 42h, T= 90 - 95 °C Guoqiang, Lin; Hjalmarsson, Mats; Hoegberg, Hans-Erik; Jernstedt, Karen; Norin, Torbjoern; Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry; vol. 38; nb. 9; (1984); p. 795 - 802 View in Reaxys

H

O

H

N

O

HO O

O

Rx-ID: 19199538 View in Reaxys 86/90 Yield

Conditions & References Reaction Steps: 3 1: 83 percent / Mg / diethyl ether / reflux, 4 h -> ambient temperature

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

2: LDA / tetrahydrofuran / -100 deg C, 2 h -> -50 deg C 3: 3 M aq. HCl / dioxane / 42 h / 90 - 95 °C With hydrogenchloride, magnesium, lithium diisopropyl amide in tetrahydrofuran, 1,4-dioxane, diethyl ether Guoqiang, Lin; Hjalmarsson, Mats; Hoegberg, Hans-Erik; Jernstedt, Karen; Norin, Torbjoern; Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry; vol. 38; nb. 9; (1984); p. 795 - 802 View in Reaxys Reaction Steps: 3 1: 83 percent / Mg / diethyl ether / reflux, 4 h -> ambient temperature 2: LDA / tetrahydrofuran / -100 deg C, 2 h -> -50 deg C 3: 76 percent / 3 M aq. HCl / dioxane / 42 h / 90 - 95 °C With hydrogenchloride, magnesium, lithium diisopropyl amide in tetrahydrofuran, 1,4-dioxane, diethyl ether Guoqiang, Lin; Hjalmarsson, Mats; Hoegberg, Hans-Erik; Jernstedt, Karen; Norin, Torbjoern; Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry; vol. 38; nb. 9; (1984); p. 795 - 802 View in Reaxys

H

O

N

HO O

OH

Rx-ID: 19210597 View in Reaxys 87/90 Yield

Conditions & References Reaction Steps: 2 1: LDA / tetrahydrofuran / -100 deg C, 2 h -> -50 deg C 2: 3 M aq. HCl / dioxane / 42 h / 90 - 95 °C With hydrogenchloride, lithium diisopropyl amide in tetrahydrofuran, 1,4-dioxane Guoqiang, Lin; Hjalmarsson, Mats; Hoegberg, Hans-Erik; Jernstedt, Karen; Norin, Torbjoern; Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry; vol. 38; nb. 9; (1984); p. 795 - 802 View in Reaxys Reaction Steps: 2 1: LDA / tetrahydrofuran / -100 deg C, 2 h -> -50 deg C 2: 76 percent / 3 M aq. HCl / dioxane / 42 h / 90 - 95 °C With hydrogenchloride, lithium diisopropyl amide in tetrahydrofuran, 1,4-dioxane Guoqiang, Lin; Hjalmarsson, Mats; Hoegberg, Hans-Erik; Jernstedt, Karen; Norin, Torbjoern; Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry; vol. 38; nb. 9; (1984); p. 795 - 802 View in Reaxys

O

H

O

HO O

Rx-ID: 1156924 View in Reaxys 88/90 Yield

Conditions & References With sodium hydroxide, η-chymotrypsin Cohen,S.G.; Milovanovic,A.; Journal of the American Chemical Society; vol. 90; (1968); p. 3495 - 3502 View in Reaxys

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(S)-alpha-Methylhydrocinnamic acid [C10H12O2]

H

(+-)-2-methyl-3-phenyl-propionic acid

HO O

Rx-ID: 7672198 View in Reaxys 89/90 Yield

Conditions & References With Quinine Kenyon; Ross; Journal of the Chemical Society; (1951); p. 3407,3409 View in Reaxys Akabori; Sakurai; Nippon Kagaku Zasshi; vol. 78; (1957); p. 1629; ; (1959); p. 21687 View in Reaxys DeTar; Weis; Journal of the American Chemical Society; vol. 79; (1957); p. 3045,3048 View in Reaxys Nerdel; John; Chemische Berichte; vol. 89; (1956); p. 1945,1949 View in Reaxys

H

H

(+-)-2-methyl-3-phenyl-propionic acid H 2N HO O

Rx-ID: 7672199 View in Reaxys 90/90 Yield

Conditions & References Schrecker; Journal of Organic Chemistry; vol. 22; (1957); p. 33 View in Reaxys

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