Overlap control aldol reaction

The high selectivity for the synclinal transition structure in these models may also arise from frontier orbital interactions. Anh and Thanh have suggested that the stereochemical outcome of an aldol reaction may be controlled by the overlap between the frontier molecular orbitals [23aJ. This same cycloaddition-like transition structure was first used by Mulzer to explain the high selectivity observed in... 

A procedure has been developed which extends the Darzens synthesis to the preparation of aziridine esters and amides (equation 29). Reaction of benzalaniline (80) and ethyl chloroacetate (in BuKDK/DME) results in the formation of the trans-aziridine (82a) in 29% yield analysis of the crude reaction mixture showed no more than 10% of the isomeric cis adduct (83a). Similarly, condensation of 2-chloro-N,N-diethylacetamide and (80) affords aziridines (82b) and (83b) in 65% yield. However, in this case the cis isomer predominates ( 90 10, cis trans). The formation of (83a R = OEt) as the major product is consistent with the overlap control model suggested by Zimmerman. Apparently, the decreased stability of the amide (81b) enolate relative to the ester (81a) enolate causes ki (cyclization) to become greater than k (addition Scheme 19) it follows that the stereochemical outcome is determined in the initial aldol step, and steric arguments are advanced to explain this outcome. 

Which electrophile is lost from the amino acid residue is, of course, controlled by the enzyme. One way this may occur is by the enzyme binding the PLP imine so that the electrophile is in close proximity to a suitable or base to aid abstraction and also so that the a orbital of the bond to be broken is periplanar with the p r acceptor system, i.e. orthogonal to the plane of the pyridine ring (XXXI). Maximal orbital overlap, stereoelectronic control, will lower the activation energy for the reaction. Aldol-type reactions can also occur with PLP as in the laboratory the key to making carbon-carbon bonds is the formation of a stabilised carbanion. Proton abstraction from the initially formed imine gives a masked carbanion which can nucleophili-... 

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