Cycloadditions Reformatsky reagents

The alternative [2 + 2] cycloaddition route to azetidinones, using chloro-sulphonyl isocyanate and functionalized alkenes, has been further used in syntheses of /8-lactam antibiotics. Asymmetric induction in the formation of /3-amino-aa-dimethyl-/8-phenylpropionic acid has been achieved, using a Reformatsky reagent and a chiral Schifif base, the reaction proceeding through a /3-lactam intermediate. ... 

Enantiomerically pure trans-2-phenylcyclohexanol, first used by Whitesell as a chiral auxiliary has become a popular reagent in a number of asymmetric transformations. Some recent applications include asymmetric azo-ene reactions, [4 + 2]-cycloaddition reactions, ketene-olefin [2 + 2]-reactions, enolate-imine cyclocondensations, Pauson-Khand reactions," palladium annulations and Reformatsky reactions. Despite its potential, use of this chiral auxiliary on a preparative scale is currently limited by its prohibitive cost. 

The condensation of an imine with a Reformatsky-type reagent and tandem reactions can result in asymmetric induction.3-207-484 87 The reaction of a ketene with an electron-rich alkene results in a [2+2] cycloaddition, although other systems can also be used,488 90 The stereochemistry of the adduct is cis, and functionalized ketenes can also be used. The ketene can be generated in situ (Scheme 26.21).491... 

The Reformatsky reactions of methyl or ethyl bromoacetate with 4-acetoxy-,2,24 4-benzyloxy-,2 4-tetrahydropyranyloxy-,2 4-chloro-,8 and 4,4-dimethoxy-2-butanone1418 have been carried out. The adducts were converted to mevalonolactone by hydrolysis and, in the case of the acetal reactant, by appropriate reduction and oxidation procedures. The same Reformatsky-type syntheses of mevalonolactone have also been performed using the lithium and magnesium carbanions of acetate esters5,19 25 26 and the dianion of acetic acid28,27 instead of the usual zinc reagent. The intramolecular Reformatsky reaction of 4-(bromoacetoxy)-2-butanone gives mevalonolactone directly.28 A related route to mevalonolactone involves boron trifluoride-catalyzed cycloaddition of ketene to 4-acetoxy-2-butanone followed by hydrolysis.183... 

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