CP-225,917 synthetic studies: unusual hydroboration regioselectivity influenced by remote functional groups

Hydroboration–oxidation of 1,1-disubstituted alkenes with borane–methyl sulfide complex in bridged tricyclic intermediates of the CP-225,917 ring system were observed to produce significant quantities of tertiary alcohol products. This net Markovnikov addition of water across an alkene is influenced by a combination of remote functional groups. Computations at the B3LYP/6-31G∗ level of theory correctly predicted this reversal in selectivity and directed the selective removal of functional groups to restore selectivity for the primary alcohol.