Synthesis of oxazolidines using DMSO/P4O10 as a formaldehyde equivalent

Compounds containing a substituted oxazolidine ring were prepared in excellent yields in two steps from cis or trans 3-phenylglycidate. When an electron donating amine was used in the nucleophilic opening of an epoxide, treatment of the resulting β-amino-α-hydroxy ester with DMSO/P4O10 led to the formation of cis or trans oxazolidines. This simple and practical procedure was readily adapted to the synthesis of enantiopure oxazolidines, using DMSO/P4O10 because of the availability of the enantiopure halohydrins from enzymatic reduction of the β-chloro-α-ketoester.

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(2S,3S)-(+)-Methyl-3-chloro-2-hydroxy-3-phenylpropanoateC10H11ClO3Ee = >99%[α]D25=+46 (c 1.07, CH2Cl2)Source of chirality: enzyme SSCR resolutionAbsolute configuration: (2S,3S)

(2R,3R)-(+)-Methyl 3-phenylglycidateC10H10O3Ee = >99%[α]D25=+10.8 (c 1.03, CH2Cl2)Source of chirality: enantiopure reactantAbsolute configuration: (2R,3R)

(2R,3S)-(+)-Methyl 3-(4-methoxyphenylamino)-2-hydroxy-3-phenylpropanoateC17O4NH19Ee = >99%[α]D25=+10.3 (c 0.99, CH2Cl2)Source of chirality: enantiopure reactantAbsolute configuration: (2R,3S)

(2R,3S)-(+)-Methyl 3-(4-chlorophenylamino)-2-hydroxy-3-phenylpropanoateC16H16ClO3NEe = >99%[α]D25=+7.86 (c 1.36, CH2Cl2)Source of chirality: enantiopure reactantAbsolute configuration: (2R,3S)

(4S,5R)-(+)-Methyl 3-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylateC18O4NH19Ee = >99%[α]D25=+48.7 (c 1.02, CH2Cl2)Source of chirality: enantiopure reactantAbsolute configuration: (4S,5R)

(4S,5R)-(+)-Methyl 3-(4-chlorophenyl)-4-phenyl-1,3-oxazolidine-5-carboxylateC17O3NClH16Ee = >99%[α]D25=+36.1 (c 0.55, CH2Cl2)Source of chirality: enantiopure reactantAbsolute configuration: (4S,5R)