Organocatalytic sequential α-aminoxylation and cis-Wittig olefination of aldehydes: synthesis of enantiopure γ-butenolides

A short route to enantiopure γ-butenolides (up to 99% ee) has been developed from readily available starting materials. The strategy involves a sequential organocatalytic α-aminoxylation followed by cis-Wittig olefination of aldehydes. The utility of this protocol has been demonstrated in the asymmetric synthesis of trans-(+)-cognac lactone with high enantiomeric purity.

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(R)-5-Propylfuran-2(5H)-oneC7H10O2Ee 99% determined by chiral HPLC[α]D25=-102.6 (c 1, CHCl3)Source of chirality: l-proline-catalyzed α-aminoxylationAbsolute configuration: (R)

(R)-5-(4-Methoxybenzyl)furan-2(5H)-oneC12H12O3Ee 98% determined by chiral HPLC[α]D25=-159.0 (c 1, CHCl3)Source of chirality: l-proline-catalyzed α-aminoxylationAbsolute configuration: (R)

(R)-5-(3-((tert-Butyldiphenylsilyl)oxy)propyl)furan-2(5H)-oneC23H28O3SiEe 99% determined by chiral HPLC[α]D25=-38.9 (c 1, CHCl3)Source of chirality: l-proline-catalyzed α-aminoxylationAbsolute configuration: (R)

(R)-(E)-Ethyl 4-hydroxyhept-2-enoateC9H16O3[α]D25=-21.0 (c 1, CHCl3)Ee 99% determined by chiral HPLCSource of chirality: l-proline-catalyzed α-aminoxylationAbsolute configuration: (R)

(R)-(E)-Ethyl 4-hydroxynon-2-enoateC11H20O3[α]D25=-21.0 (c 1, CHCl3)Source of chirality: l-proline-catalyzed α-aminoxylationAbsolute configuration: (R)

(R)-(E)-Ethyl 7-((tert-butyldiphenylsilyl)oxy)-4-hydroxyhept-2-enoateC25H34O4Si[α]D25=-8.4 (c 1, CHCl3)Source of chirality: l-proline-catalyzed α-aminoxylationAbsolute configuration: (R)