A concise enantioselective synthesis of (+)-decarestrictine L via proline-catalyzed sequential α-aminooxylation and Horner–Wadsworth–Emmons olefination

A short enantioselective synthesis of (+)-decarestrictine L, a cholesterol biosynthesis inhibitor metabolite, is described using a d-proline catalyzed sequential α-aminooxylation and a Horner–Wadsworth–Emmons olefination.

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(S)-2-[4-(Benzyloxy)butyl]oxiraneC13H18O2Ee 99% determined by chiral HPLC[α]D25=-5.1 (c 2.0, CHCl3)Source of chirality: hydrolytic kinetic resolutionAbsolute configuration: (S)

(R)-6-(Benzyloxy)hexan-2-olC13H20O2Ee 99% determined by chiral HPLC[α]D25=-7.9 (c 2.0, CHCl3)Source of chirality: hydrolytic kinetic resolutionAbsolute configuration: (R)

(R)-[6-(Benzyloxy)hexan-2-yloxy]-tert-butyldimethylsilaneC19H34O2Si[α]D25=-10.0 (c 1.0, CHCl3)Source of chirality: hydrolytic kinetic resolutionAbsolute configuration: (R)

(R)-5-(tert-Butyldimethylsilyloxy)hexan-1-olC12H28O2Si[α]D25=-13.8 (c 1.6, CHCl3)Source of chirality: hydrolytic kinetic resolutionAbsolute configuration: (R)

(R)-5-(tert-Butyldimethylsilyloxy)hexanalC12H26O2Si[α]D25=-12.0 (c 3.0, CHCl3)Source of chirality: hydrolytic kinetic resolution/asymmetric reductionAbsolute configuration: (R)

(R)-Ethyl 5-tert-butyldimethylsiloxyhex-2-enoateC14H28O3Si[α]D25=-15.8 (c 2.4, CHCl3)Source of chirality: asymmetric reductionAbsolute configuration: (R)

Aminooxy-olefinic ketoneC21H35NO3Si[α]D25=-12.5 (c 4.0, CHCl3)Source of chirality: asymmetric reduction/HKR and sequential α-aminooxylation–olefinationAbsolute configuration: (5S,8R)