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.

Remote functional groups influence hydroboration of an exocyclic olefin leading to higher than expected levels of 3° alcohol products.