Indirect Tertiary Alcohol Enantiocontrol by Acylative Organocatalytic Kinetic Resolution

Abstract

The stereocontrol of tertiary alcohols represents a recurrent challenge in organic synthesis. In the present paper, we describe a simple, efficient, and indirect method to enantioselectively prepare tertiary alcohols through a chiral isothiourea catalyzed selective acylation of adjacent secondary alcohols. This transformation enables the kinetic resolution (KR) of easily prepared racemic diastereoenriched secondary/tertiary diols providing both monoesters and starting diols in highly enantioenriched forms (s-value >200).

Recent Advances in Catalytic Nonenzymatic Kinetic Resolution of Tertiary Alcohols

“…A similar protocol was reported in 2021 by Bressy, Quintard, and co-workers, who employed only 1 mol% of Hyper-BTM 49 as the chiral catalyst (Scheme 11b). 34 This approach allowed the KR of racemic diastereoenriched tertiary diols with selectivity factors up to 200 by selective acylation of the neighboring secondary alcohol.…”

Ready Access to Densely Substituted Furans Using Tsuji–Wacker-Type Cyclization

“…1,2-Diphenylpent-4-ene-1,2-diol (10d). 31 Compound 10d was synthesized by following general procedure B and purified by silica gel column chromatography (90:10 petroleum ether/ethyl acetate): isolated yield of 0.235 g, 78%, white solid; IR υ max (film) 3393, 3061, 2920, 1447, 1035 cm −1 ; 1 H NMR (400 MHz, CDCl 3 ) δ 7.18− 7.05 (m, 8H), 6.93 (dt, J = 3.6, 2.4 Hz, 2H), 5.50 (dddd, J = 17.1, 10.1, 8.8, 5.7 Hz, 1H), 5.13−5.00 (m, 2H), 4.73 (s, 1H), 2.87 (ddt, J = 14.2, 5.7, 1.4 Hz, 1H), overlap 2.69 (dd, J = 14.2, 8.8 Hz, 2H), 2.54 (s, 1H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 141. 4, 139.3, 133.2, 127.8, 127.6, 127.4, 126.5, 119.8, 80.4, 78.3, 42.4; HRMS (ESI) m/z [M + Na] + calcd for C 17 H 18 O 2 Na 277.1199, found 277.1198.…”

“…4, 147.6, 139.1, 136.8, 133.7, 127.9, 126.7, 125.8, 125.6, 119.7, 80.6, 78.3, 41.9, 33.9, 33.7, 24.1, 24. 1,2-Bis(4-methoxyphenyl)pent-4-ene-1,2-diol (10g). 31 Compound 10g was synthesized by following general procedure B and purified by silica gel column chromatography (70:30 petroleum ether/ethyl acetate): isolated yield of 0.230 g, 97%, white solid; IR υ max (film) 3490, 2922, 1609, 1245, 1179 cm −1 ; 1 H NMR (400 MHz, CDCl 3 ) δ 7.08−7.04 (m, 2H), 6.95−6.91 (m, 2H), 6.78−6.74 (m, 2H), 6.73−6.69 (m, 2H), 5.64−5.54 (m, 1H), 5.18 (dt, J = 17.2, 2.4 Hz, 1H), 5.11−5.08 (m, 1H), 4.75 (d, J = 4.1 Hz, 1H), 3.78 (s, 3H), 3.76 (s, 3H), 2.88 (ddt, J = 14.1, 5.7, 1.4 Hz, 1H), 2.69 (dd, J = 14.2, 8.7 Hz, 1H), 2.60 (d, J = 4.2 Hz, 1H), 2.53 (s, 1H) 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 159.0, 158.4, 133.5, 133.4, 131.5, 128.9, 127.9, 119.7, 112.9(2C) 5, 157.9, 133.6, 133.5, 131.5, 129.1, 128.0, 119.8, 113.6(2C), 80.4, 78.3, 63.4, 42.5, 15. 1,2-Bis(4-ethylphenyl)pent-4-ene-1,2-diol (10i). Compound 10i was synthesized by following general procedure B and purified by silica gel column chromatography (80:20 petroleum ether/ethyl acetate): isolated yield of 0.283 g, 97%, white solid, as a diastereomeric mixture; IR υ max (film) 3361, 2970, 1655, 1305, 1119 cm −1 ; 1 H NMR (400 MHz, CDCl 3 ) δ 7.17 143.0, 138.9, 136.7, 133.6, 127.9, 127.3, 127.1, 126.8, 119.8, 80.6, 78.4, 42.2, 28.6, 28.5, 15.7, 15.6; HRMS (ESI) m/z [M + Na] + calcd for C 21 H 26 O 2 Na 333.1825, found 333.1820.…”

Copper-Catalyzed Asymmetric Oxidative Desymmetrization of 2-Substituted 1,2,3-Triols

“…Despite the great progress in the asymmetric synthesis of chiral tert -alcohols, − the efficient strategies to prepare enantiomerically enriched glycerol and related derivatives are still underdeveloped. Sharpless–Katsuki asymmetric dihydroxylation and asymmetric epoxidation-nucleophilic ring-opening sequence of 1,1-disubstituted olefins are powerful and reliable approaches to substituted glycerol derivatives. , Enantioselective aldol reactions of α-ketoesters and asymmetric substitution or oxidation reactions of malonate and β-ketoester derivatives would be alternative methods, though additional transformations are commonly required to obtain glycerol and their oxidized derivatives.…”