Synthesis of modular thiophene-oxazoline ligands and their application in the asymmetric phenyl transfer reaction to aldehydes

A series of thiophene mono (oxazoline) N,O-ligands with three sites of diversity were synthesized concisely in two steps from the corresponding thiophene carbonitriles. These ligands were applied to the enantioselective phenyl transfer reaction of aldehydes, resulting in the corresponding chiral diaryl methanol products with excellent yields and moderate to good enantioselectivities.

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(R)-(4-Chlorophenyl)(phenyl)methanolEe = 82%[α]D20=-15.4 (c 0.80, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-(4-Bromophenyl)(phenyl)methanolEe = 72%[α]D25=-16.4 (c 0.87, PhH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-(4-Methoxyphenyl)(phenyl)methanolEe = 78%[α]D25=+11.4 (c 0.67, PhH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Phenyl(p-tolyl)methanolEe = 75%[α]D25=+6.1 (c 0.50, PhH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-(2-Bromophenyl)(phenyl)methanolEe = 65%[α]D25=+36.1 (c 1.10, acetone)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-(3-Bromophenyl)(phenyl)methanolEe = 65%[α]D25=-18.1 (c 1.10, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Naphthalen-2-yl(phenyl)methanolEe = 73%[α]D25=+4.1 (c 0.82, PhH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-(2,4-Dichlorophenyl)(phenyl)methanolEe = 60%[α]D25=+4.6 (c 3.35, acetone)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(S,E)-1,3-Diphenylprop-2-en-1-olEe = 74%[α]D25=-28.1 (c 0.44, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)