Inversion of secondary chiral alcohols in toluene with the tunable complex of R3NR′COOH

The SN2 reaction of enantiomerically pure sulfonates with the tunable complex of R3N–R′COOH in toluene has been extensively studied. It was revealed that the molar ratio of the tertiary amines and carboxylic acids in the complex of R3NR′COOH is crucial for the SN2 reaction, and should be tuned for each sulfonate to give the best yield. Fifteen sulfonates 1 and 3–13 (Scheme 2) were prepared and transformed into 22 corresponding inverted esters 2 and 14–24 (Scheme 2) in good to high yields.

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(R)-1-(2,3-Difluoro-6-nitrophenoxy)propan-2-yl formateC10H9F2NO5[α]D20=+22.0 (c 4.5, CHCl3)Source of chirality: alcohol inversionAbsolute configuration: (R)

(R)-1-(2,3-Difluoro-6-nitrophenoxy)propan-2-yl acetateC11H11F2NO5[α]D20=+35.0 (c 6.7, CHCl3)Source of chirality: alcohol inversionAbsolute configuration: (R)

(R)-1-(2,3-Difluoro-6-nitrophenoxy)propan-2-yl benzoateC16H13F2NO5[α]D20=-21.0 (c 4.1, CHCl3)Source of chirality: alcohol inversionAbsolute configuration: (R)

(3S,4S,5R)-Ethyl 3-acetoxy-5-benzoyloxy-4-(methylsulfonyloxy)cyclohex-1-ene carboxylateC19H22O9S[α]D20=-36.8 (c 2.1, EtOAc)Source of chirality: alcohol inversionAbsolute configuration: (3S,4S,5R)

(3S,4S,5R)-Ethyl 3,5-dibenzoyloxy-4-(methylsulfonyloxy)cyclohex-1-ene carboxylateC24H24O9S[α]D20=+15.1 (c 1.5, EtOAc)Source of chirality: alcohol inversionAbsolute configuration: (3S,4S,5R)

Cholest-5-en-3α-yl acetateC29H48O2[α]D20=-12.0 (c 1.5, CHCl3)Source of chirality: alcohol inversionAbsolute configuration: (3R)

Cholest-5-en-3α-yl benzoateC34H50O2[α]D20=-18.9 (c 1.5, CHCl3)Source of chirality: alcohol inversionAbsolute configuration: (3R)

5α-Cholestan-3α-yl acetateC29H50O2[α]D20=+24.8 (c 1.6, CHCl3)Source of chirality: alcohol inversionAbsolute configuration: (3R)

5α-Cholestan-3α-yl benzoateC34H52O2[α]D20=+25.6 (c 1.5, CHCl3)Source of chirality: alcohol inversionAbsolute configuration: (3R)

17α-Estra-3-methanesulfonyloxy-17-yl benzoateC26H30O5S[α]D20=-9.2 (c 2.1, acetone)Source of chirality: alcohol inversionAbsolute configuration: (17R)

(R)-1-Phenylpropan-2-yl acetateC11H14O2[α]D20=+28.5 (c 4.0, benzene)Source of chirality: alcohol inversionAbsolute configuration: (R)

((2S,3S,4R,5R)-3,4-Diacetoxy-2-((2R,3R,4S,5S,6R)-3,4,5-triacetoxy-6-acetoxymethyl-tetrahydro-2H-pyran-2-yloxy)-tetrahydrofuran-2,5-diyl) bis(methylene) dibenzoateC38H42O19[α]D20=+52.5 (c 0.5, acetone)Source of chirality: alcohol inversionAbsolute configuration: (2S,3S,4R,5R)

(2R,3R,5R)-2-(Acetoxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-tetrahydrofuran-3-yl benzoateC19H20N2O7[α]D20=+74.5 (c 1.5, acetone)Source of chirality: alcohol inversionAbsolute configuration: (2R,3R,5R)

(2R,3R,5R)-2-(Benzoyloxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-tetrahydrofuran-3-yl benzoateC24H22N2O7[α]D20=+66.0 (c 1.3, acetone)Source of chirality: alcohol inversionAbsolute configuration: (2R,3R,5R)

(R)-Ethyl 3-acetoxy-butanoateC8H14O2[α]D20=+2.9 (c 1.0, CHCl3)Source of chirality: alcohol inversionAbsolute configuration: (R)

(R)-Ethyl 3-benzoyloxy-butanoateC13H16O4[α]D20=-16.0 (c 1.4, CHCl3)Source of chirality: alcohol inversionAbsolute configuration: (R)

(R)-4-(4-Tosyloxyphenyl)butan-2-yl acetateC19H22O5S[α]D20=+3.3 (c 4.2, acetone)Source of chirality: alcohol inversionAbsolute configuration: (R)

(1S,2S,5R)-2-Isopropyl-5-methylcyclohexyl formateC11H20O2[α]D20=+24.0 (c 2.4, EtOH)Source of chirality: alcohol inversionAbsolute configuration: (1S)

(1S,2S,5R)-2-Isopropyl-5-methylcyclohexyl acetateC12H22O2[α]D20=+35.6 (c 2.4, EtOH)Source of chirality: alcohol inversionAbsolute configuration: (1S,2S,5R)

(1S,2S,5R)-2-Isopropyl-5-methylcyclohexyl benzoateC17H24O2[α]D20=+13.0 (c 2.4, EtOH)Source of chirality: alcohol inversionAbsolute configuration: (1S,2S,5R)

(1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl acetateC12H22O2[α]D20=-80.4 (c 2.1, CHCl3)Source of chirality: alcohol inversionAbsolute configuration: (1R,2S,5R)

(1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl benzoateC17H24O2[α]D20=-91.2 (c 1.3, CHCl3)Source of chirality: alcohol inversionAbsolute configuration: (1R,2S,5R)