Lewis Acid‐Catalyzed Stereoselective α‐Addition of Chiral Aldehydes to Cyclic Dienol Silanes: Aqueous Synthesis of Chiral Butenolides

Abstract

The stereoselective α-addition to cyclic dienol silanes has rarely been exploited, in contrast to the well-studied γ-addition of conjugated butenolides. In this study, an unprecedent catalytic Mukaiyama aldol α-addition of 2-trimetylsiloxy furan to optically pure aldehydes in water-containing solvents is reported. The synthetic utility of this concept was demonstrated in the efficient synthesis of six bioactive natural products: vitexolide D, curcucomosin C, villosin, chinensine C, (+)-coronarin E and (E)-labda-7,11,13-trien-16,15-olid.

Mukaiyama aldol reaction: an effective asymmetric approach to access chiral natural products and their derivatives/analogues

“…81,82 These are also used as effective pain killers. In this regard, Adamkiewicz et al 83 reacted sclareolide 131 with CH 3 NHOCH 3 in the presence of HCl, AlMe 3 and dichloromethane, followed by its reaction with thionyl chloride and then subsequent reduction resulted in the synthesis of compound 132 in 90% yield. Compound 132 was further reacted with silyl enol ether 133 via the Yb(OTf) 3 catalyzed Mukaiyama aldol reaction, which resulted in the mixture of curcucomosin 134 and vitexolide 135 in 70% yield (5 : 1).…”