Mechanistic studies of the molybdenum-catalyzed asymmetric alkylation reaction.
Enantiomerically enriched, deuterated branched carbonates (Z)-(S)-PhCH(OCO(2)Me)-CH = CHD (1-D), (Z)-(R)-PhCH(OCO(2)Me)CH = CHD (2-D), and linear carbonate (E)-(S)-PhCH = CHCHD(OCO(2)Me) (3-D) were used as probes in the Mo-catalyzed asymmetric allylic alkylation with sodium dimethyl malonate, catalyzed by ligand-complex 11 derived from the mixed benzamide/picolinamide of (S,S)-transdiaminocyclohexane and (norbornadiene)Mo(CO)(4). The results of these studies, along with x-ray crystallography and solution NMR structural analysis of the pi-allyl intermediate, conclusively established the reaction proceeded by a retention-retention pathway. This mechanism contrasts with that defined for Pd-catalyzed allylic alkylations, which proceed by an inversion-inversion pathway. A proposed rationale for the retention pathway for nucleophilic substitution involves CO-coordination to form a tri-CO intermediate, followed by complexation with the anion of dimethyl malonate to produce a seven-coordinate intermediate, which reductively eliminates to afford product with retention of configuration.
Hughes
David L
DL
Department of Process Research, Merck Research Laboratories, Merck and Co., Inc., Rahway, NJ 07065, USA. dave_hughes@merck.com
Lloyd-Jones
Guy C
GC
Krska
Shane W
SW
Gouriou
Laure
L
Bonnet
Veronique D
VD
Jack
Kevin
K
Sun
Yongkui
Y
Mathre
David J
DJ
Reamer
Robert A
RA