MUKAIYAMA ALDOL REACTIONS CATALYZED BY ZIRCONOCENE BIS(TRIFLATE) COMPLEXES - STEREOCHEMISTRY AND MECHANISMS FOR C-C BOND FORMATION

The aldol condensations of alpha- and beta-(benzyloxy) aldehydes with enol silanes, catalyzed by Cp2Zr(OTf)(2) . THF or Cp2Zr(OTf)(2), in a variety of solvents were studied. The simple diastereoselectivity of t hese reactions is modest and comparable to that observed using simple aldehydes of similar steric requirements. Studies have revealed that T MSOTf is directly produced on reaction with the zirconocene catalyst w ith the enol silane in nitroalkane solvent or is formed during catalys is in dichloromethane solution. Although TMSOTf is known to catalyze c ross-aldol reactions under these conditions, the rate of this process is not always competitive with that observed using the zircanocene cat alysts. In particular, sterically unhindered or aromatic aldehydes rea ct via a mechanism that appears to be mainly Zr-catalyzed, based on bo th the difference in rate between Zr- and Si-mediated reactions as wel l as differences in enol silane/silyl triflate reactivity in crossover -type experiments. With sterically hindered aldehydes in dichlorometha ne or nitromethane, catalysis is mediated by Si. The Zr-catalyzed proc ess occurs via formation of a Zr-aldolate complex from aldehyde and en ol silane, with liberation of TMSOTf, followed by rate-limiting O-sily latian of the metal aldolate by TMSOTf, as revealed by both model stud ies and in situ monitoring during catalysis.