Synfacts 2007(5): 0514-0514  
DOI: 10.1055/s-2007-968454
Metal-Catalyzed Asymmetric Synthesis and Stereoselective Reactions
© Georg Thieme Verlag Stuttgart · New York

Mechanistic Dichotomy: Cu(II)- and Enzyme-Catalyzed Aldol Reaction

Contributor(s):Hisashi Yamamoto, Matthew B. Boxer
K. C. Fortner, M. D. Shair*
Harvard University, Cambridge, USA
Stereoelectronic Effects Dictate Mechanistic Dichotomy between Cu(II)-Catalyzed and Enzyme-Catalyzed Reactions of Malonic Acid Half Thioesters
J. Am. Chem. Soc.  2007,  129:  1032-1033  
Further Information

Publication History

Publication Date:
24 April 2007 (online)


Significance

This is a nice mechanistic follow-up comparing the Shair group’s previously reported catalytic asymmetric thioester aldol reaction to the enzymatic mechanism (M. Shair and co-workers J. Am. Chem. Soc. 2005, 127, 7284-7285). Kinetics, kinetic isotope effects (both deuterium and 13C), and crossover experiments were performed and it was concluded that the two systems react under distinct mechanisms. The Cu(II)-catalyzed reaction undergoes the aldol reaction followed by decarboxylation while the enzymatic version undergoes decarboxylation to form the enolate, which then acts in the aldol reaction.

Comment

The asymmetric thioester aldol reaction developed by this group is quite interesting and allows comparison of the biosynthesis of polyketides and fatty acids to the standard ‘flask’ aldol reaction. The finding reiterates the intricacy of enzymes and also traces back to fundamental stereoelectronic effects that strongly govern reaction mechanisms. The s-p* overlap in the decarboxylative step for the enzyme is not present in the Cu(II) system and therefore they proceed through different mechanisms.