Correction: Mechanochemical enzymatic resolution of N-benzylated-β3-amino esters

• Published in: Beilstein journal of organic chemistry 2017-01, Vol.13 (1), p.2128-2130
• Main Authors: Pérez-Venegas, Mario, Reyes-Rangel, Gloria, Neri Adrián, Escalante, Jaime, Juaristi Eusebio
• Format: Article
• Language: English
• Subjects: ball-milling; Candida antarctica lipase B; Chemistry; Chromatography; enzymatic resolution; Esters; mechanochemistry; β3-amino acid
• ISSN: 2195-951X; 1860-5397; 1860-5397
• DOI: 10.3762/bjoc.13.210

Table 1 Search of the best parameters in the enzymatic enantioselective hydrolysis of rac-1a under ball milling. entrya LAG additiveb yield (%)c (S)-1a/(R)-2a time (h) ee (S)-1a (%)d ee (R)-2a (%)d c e (%) E f 1g 2M2B 51/49 0.5 99 80 55 46 2 2M2B 70/30 0.5 89 77 54 23 3 2M2B 51/49 1 99 95 51 >200 4 AcOEt 86/13 1 69 95 42 81 5 IPA 80/20 1 48 95 34 63 6 CH3CN 65/29 1 65 95 41 77 7 hexane 40/60 1 97 86 53 55 8 – 58/41 1 95 92 51 89 9g – 58/42 1 93 86 52 45 10h – 68/31 1 74 80 48 20 aReactions were carried out with 0.5 equivalents of water and 15 Hz of frequency. b0.2 mL of LAG additive was used. cDetermined after purification by flash chromatography. dDetermined by HPLC with chiral stationary phase. eCalculated from c = ees/(ees + eep). f E = ln[1 − c(1 + eep)]/ln[1 − c(1 − eep)]. g25 Hz of frequency was used. h0.25 equivalents of water were used. Table 2 Substrate scope for the enzymatic resolution of N-benzylated-β3-amino esters. entrya rac R yield (%)b (S)-1/(R)-2 eec (S)-1(%) eec (R)-2(%) c f (%) E g absolute configurationh 1 1b CH3-(CH2)- 51/49 91 4.5 97 −36.5 48 >200 R 2 1c CH3-(CH2)2- 53/43 84 2.1 98 −45.2 46 >200 R 3 1d CH3-(CH2)3- 68/29 23 2.0 94 −35.3 20 40 R 4 1e CH3-(CH2)4- 74/24 16 0.2 94 −40.0 15 38 R 5 1f CH3-(CH2)5- 79/18 13 0.8 91 −39.7 13 24 R 6i 1g Ph 90/10 18 3.4 83 −35.0 18 13 S 7i 1h 4-MeO-Ph 89/10 1 −0.5 80 −31.7 1 9 S 8 1i t-Bu 89/4 4 −0.6 94 12.8 4 34 S aReactions were carried out with 0.5 equivalents of water and 0.2 mL of 2M2B at 15 Hz during 1 h. bDetermined after purification by flash chromatography. cDetermined by HPLC with chiral stationary phase. d c = 0.33 in CH3Cl. e c = 0.33 in MeOH. fCalculated from c = ees/(ees + eep). g E = ln[1 − c(1 + eep)]/ln[1 − c(1 − eep)]. hAssigned by chemical correlation and by HPLC with chiral stationary phase. i0.75 equivalents of water were used. Table 4 Scaling-up of the enzymatic hydrolysis reaction under ball-milling using substrate rac-1a. entrya catalyst/substrate (equiv) b yield (%)c (S)-1a/(R)-2a eed (S)-1a (%) eed (R)-2a (%) c e (%) E f 1g 1/1 51/49 >99 95 51 >200 2 1/3 52/48 62 93 40 52 3 1/6 61/38 53 93 36 47 4 1/9 59/40 49 94 34 53 aReactions were carried out with 0.5 equivalents of water at 15 Hz during 1 h. b1 equivalent of enzyme = 40 mg; 1 equivalent of susbtrate = 82 mg. cDetermined after purification by flash chromatography. dDetermined by HPLC with chiral stationary phase. eCalculated from c = ees/(ees + eep). f E = ln[1 − c(1 + ee p)]/ln[1 − c(1 − ee p)]. g0.2 mL of LAG were