Enantioenriched sp³-hybridized stereogenic carbanions present many tantalizing possibilities for asymmetric synthesis; however, comparatively few synthetic methods based on the deployment of such fundamentally important species have emerged to date. In pursuit of a unified method for controlled carbon-carbon bond formation, we reported that alpha-chloroalkylmetal reagents (Li- and Mg-carbenoids), generated in enantioenriched form by sulfoxide ligand exchange from readily available scalemic alpha-chlorosulfoxides, chain extend boronic esters with remarkable stereochemical fidelity. In principle, iteration of this stereospecific reagent controlled homologation (StReCH) process provides for a conceptually straightforward asymmetric synthetic method in which molecular constitution and stereochemical features are directly programmed by the carbenoid presentation sequence. An overview of the development of the StReCH concept from its genesis in the work of Matteson, Hoffmann, Beak, and Hoppe, to ongoing studies directed at increasing the scope of this methodology and its application to natural products synthesis, will be presented.

For background and leading references, see:

"Iterative Stereospecific Reagent Controlled Homologation Using a Functionalized alpha-Chloroalkyllithium: Synthesis of Cyclic Targets Related to Epibatidine," C. R. Emerson, L. N. Zakharov, P. R. Blakemore Org. Lett. 2011, 13, 1318-1321.