Stereocontrol olefin geometry

Prins cyclization of syn-P-hydroxy allylsilanes with aldehydes gives cis-2,6-disubstituted 4-alkylidenetetrahydropyrans (83) as sole product regardless of the aldehyde (R ) or allylsilane (R ) substituent. Complementary exocyclic stereocontrol can be achieved by reversing R and R. With yields over 90%, >95 5% control on olefin geometry and a similar cis trans ratio, the excellent stereoselectivity has been subjected to a DFT study. The products are related to natural bryostatins, and the method holds promise for other chiral pyranyl targets. 

In studies related to the synthesis of bryostatin natural products, it was shown that stereocontrolled cyclizations could be achieved in silyl-terminated Prins cyclizations (Scheme 5). ° Thus, the syn-P-hydroxy allyl silane (13) reacts with propionaldehyde to provide the cw-2,6-disubstituted 4-alkylidenetetrahydropyran (14) in excellent yield and stereocontrol of the olefin geometry (>95 5). The chemistry was examined by DPT (density functional theory) calculations, which suggested that the cyclization step occurs through a chair-like structure (15). Stereocontrol of the exocyclic double bond is thought to be a consequence of steric and electronic effects, in particular maximization of -silyl stabilization of forming carbocation center (16). 

Addition of a Lewis acid has been noted to improve the stereoselectivity (Table 12, entries 1-3). High stereocontrol is observed for products which can equilibrate via enolization (Table 12, entries 6-10) and for the sterically demanding sulfone derivative (Table 12, entry 4). Application of this methodology to EPC synthesis is illustrated by the use of lactones prepared in 8 to 9 steps from mannose (Table 12, entries 11-18)1 4. The stereochemical information within the reactive allyl ether moiety is faithfully transmitted and, remarkably, the Z geometry of the olefins is retained during formation of the vinylcyclopentanes. These more sterically hindered substrates may give mixtures of 5- and 7-membered rings (Table 12, entries 11,12, and 14-16). 

With the advent of these homogeneous catalysts, extensive investigations followed on the influence of the catalyst geometry on the stereospecificity of olefin polymerization and the origins of stereocontrol. Zambelli employed the chiral metallocene (Hla) to study the... 

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