Bryostatin 7 synthesis olefination

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). 

In contrast to the previous examples, the preferred formation of linear aldehydes was the main target in some syntheses to construct a cyclic derivative with an appropriate ring size in the next step or for simply elongating a carbon chain. The linear aldehydes are the proper intermediates for the synthesis of indolizidine alkaloids [11], the tricyclic marine alkaloid lepadiformine [12], ACE inhibitors such as MDL 27210 and its analogues [13,14], and bryostatin, a remarkably potent anticancer agent [15]. Rhodium complexes of bisphosphite ligands provide one of the best known classes of linear-selective hydroformylation catalysts for simple ot-olefins. Except for the lepadiformine intermediate, where hydroformylation was carried out in the presence of the Rh(acac)(CO)2/P(OPh)3 catalyst system, in other... 

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