Atropisomeric alpha-methyl substituted analogues of 4-(dimethylamino)pyridine: synthesis and evaluation as acyl transfer catalysts

The regioselectivity of alpha -metalation-methylation of N-BF3 adducts of 4 -(dimethylamino)pyridines as a function of beta -substitution is examined i n attempts to prepare configurationally stable atropisomeric derivatives (I and II) having an alpha -methyl substituent and a beta -biaryl stereogenic axis. The activity of some of these derivatives as catalysts for acyl tran sfer is examined and the kinetic resolution of 1-(1-naphthyl)ethanol cataly sed by alpha -methyl chiral DMAP (-)-24 is reported. A rationale for the re duced stereoselectivity of this catalyst relative to its non-alpha -substit uted analogue (-)-1 is also proposed.