Diastereoselective radical debromination approach toward divergent syntheses of syn- and anti-propionate units, coupled with enantioselective and/or diastereoselective Lewis acid-promoted aldol reactions

Article abstract of DOI:10.1016/j.tetasy.2003.06.005

A practical methodology directed to the enantioselective synthesis of polypropionate backbones, available for the synthesis of polyketide natural products, has been developed by iterative enantio- and diastereoselective Lewis acid-promoted aldol reactions, followed by diastereoselective radical debromination reactions. A chiral oxazaborolidinone-promoted aldol reaction of a racemic aldehyde, derived from 2-methyl-1,3-propanediol, with a silylketene acetal from ethyl 2-bromopropionate, resulted in highly enantioselective formation of the corresponding bromo aldol adduct, followed by radical debromination with Bu₃SnH in the presence of Et₃B to divergently give syn- and anti-propionate aldols, which are versatile stereotriads. Furthermore, elongation of the propionate units has also been achieved: the BF₃·OEt₂-promoted aldol reaction of chiral syn- and anti-α-methyl-β-protected-oxy aldehydes with the silyl nucleophile proceeded with essentially complete syn-selectivity while the TiCl₄-promoted aldol reaction resulted in fairly good anti-selectivity. The resulting bromo aldol adducts were divergently debrominated by the radical reduction to give a complete set of stereotetrads.