Trans-Oxepane synthesis

For the synthesis of the complex natural product, the terminus six-membered ketone 55 had to be transformed into an oxepane ring. For this necessary transformation, the authors were attracted by the single-carbon homologation of a pyr-anone (a sort of ring-expansion) because, in prindple, it could be used in an iterative sense at any stage of the 6-endo cydization in their poly-TH P-based synthetic approach for the synthesis of trans-fused 6,7,6 (THP-oxepane-THP) and 6,7,7 (THP-oxepane-oxepane) ring systems [28]. Treatment of ketone 55 with TMSCHN2... 

Boron trifluoride etherate promotes the fWt/a-selcctivc oxacyclization of polyepoxides derived from various acyclic terpenoid polyalkenes, including geraniol, farnesol, and geranylgeraniol, providing an efficient and stereoselective synthesis of substituted oxepanes and fused polyoxepanes. The oxacyclization transformations may mimic ringforming steps in the biosynthesis of trans-syn-trans-fused polycyclic ether marine natural products <2002JOC2515>. 

Analogous to the nucleophilic substitution methods, nucleophilic epoxide opening provides access to substituted THP adducts in a stereospecific manner. Seminal studies by Nicolaou et al. established the structural requirements necessary for regio- and stereocontrolled synthesis of THP adducts [53, 54], Regioselectivity is highly dependent on the configuration of the epoxide (Scheme 27) 8-hydroxy trans-epoxides show high selectivity for THP formation over oxepane formation... 

Geminally silylated allylsilanes, conveniently prepared by isomerization of gem-disilylalkenes with 10% Pd/C in diethyl ether [29], are used for stereoselective synthesis of trans-2,3-disubstituted oxepanes. For example, 84 reacts with benzalde-hyde to give 85 that bears trans-2-silylethenyl and phenyl groups, via an acetaliza-tion-cyclization sequence (Scheme 5.21). 

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