Rapid Total Syntheses Utilizing 'Supersilyl' Chemistry

摘要

Although more than 100 years of study have demonstrated that the aldol reaction is one of the most fundamental and effective methods for the construction of complex molecules, in particular natural products, its full potential has not been realized.Polyketides, a family of natural products, have provided chemists with a rich source of molecular architectures and biologically significant compounds. Polyketides often contain the 1,3-polyol motif, and unsurprisingly the aldol reaction has been the preferred method to access these structures. Unfortunately, however, the most selective aldol products afford ketones or esters and not aldehydes. Thus, the reported biomimetic routes require additional protection and redox steps for each iteration, thus making the preparation of long-chain polyketides excessively lengthy (poor redox economy). Therefore, interest in one-pot polyaldol cascade reactions has increased. Although, several elegant stereoselective approaches have been reported, all the methods inevitably stop after the second aldol reaction because of the cyclization of the hydroxyaldehydes or -ketones. This cyclization could be blocked if the pendant hydroxy groups were rendered non-nucleophilic by an in situ generated blocking variant, which, importantly, would afford aldehydes 2 as products. We recently reported the first high-yielding triple aldol reaction (Scheme 1 A). This cascade results in high 1,3-stereoinduction, generated from the extreme bulk of the tris(trimethylsilyl)silyl (supersilyl) group, which also retards undesired polymerization.