Enantioselective addition of thiophenylboronic acids to aldehydes using ZnEt2/Schiff-base catalytic system

Using Schiff-base amino alcohols as catalysts which were readily derived from natural amino acids in three steps, a series of valuable optically active thiophenyl methanols (4a–4n) were first obtained in good yields and high enantioselectivities (up to 96% ee) through the asymmetric addition of thiophenylboronic acid to aldehydes in the presence of ZnEt2 in toluene.

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(Phenyl)-(2′-thienyl)methanolC11H10OSEe = 93%[α]D20=-3.6 (c 1.89, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(2-Chlorophenyl)-(2′-thienyl)methanolC11H9ClOSEe = 92%[α]D20=-31 (c 1.1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(3-Chlorophenyl)-(2′-thienyl)methanolC11H9ClOSEe = 81%[α]D20=-13 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(4-Chlorophenyl)-(2′-thienyl)methanolC11H9ClOSEe = 85%[α]D20=-19 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(4-Fluorophenyl)-(2′-thienyl)methanolC11H9FOSEe = 92%[α]D20=-15 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(2-Methylphenyl)-(2′-thienyl)methanolC12H12OSEe = 94%[α]D20=-24 (c 1.3, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(R)-(4-Methylphenyl)-(2′-thienyl)methanolC12H12OSEe = 84%[α]D20=-16 (c 1.0, CHCl3)

(2-Methoxyphenyl)-(2′-thienyl)methanolC12H12O2SEe = 95%[α]D20=-20 (c 0.95, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(3-Methoxyphenyl)-(2′-thienyl)methanolC12H12O2SEe = 93%[α]D20=-10 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(4-Methoxyphenyl)-(2′-thienyl)methanolC12H12O2SEe = 96%[α]D20=-16 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(2-Bromophenyl)-(2′-thienyl)methanolC11H9BrOSEe = 95%[α]D20=-49 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(4-Bromophenyl)-(2′-thienyl)methanolC11H9BrOSEe = 92%[α]D20=-17 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(2-Naphthyl)-(2′-thienyl)methanolC15H12OSEe = 88%[α]D20=-57 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(2-Furanyl)-(2′-thienyl)methanolC9H8O2SEe = 82%[α]D20=-11 (c 1.7, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown