Reduction of C—X Bonds Reductive Coupling

Leaving groups on the a-carbon of carbonyl compounds (e.g., Br and OR) are reduced away by one-electron reducing agents. a-Bromocarbonyl compounds are reduced to the corresponding enolates by Zn in the Reformatsky reaction (Chapter 2). After the initial electron transfer, several pathways are possible, but all lead to the enolate. The enolate is usually allowed to react immediately with an electrophile such as another carbonyl compound. Before the advent of strong, non-nucleophilic bases, the Reformatsky reaction was the only way to prepare enolates of simple carbonyl compounds quantitatively. 

In the pinacol coupling, two ketones are reductively coupled to give a 1,2-diol. (Compare the photochemical pinacol coupling discussed earlier.) The two ketones are usually identical, but intramolecular dimerizations can give unsym-metiical 1,2-diols. The reaction proceeds by electron transfer to the ketone to give a ketyl radical anion. This compound dimerizes to give the 1,2-diol. 

The McMurry coupling (Chapter 6) is closely related to the pinacol coupling. 

The acyloin condensation converts two esters to an a-hydroxyketone (an acy-loin), often in an intramolecular fashion. The reaction proceeds by a mechanism very similar to the pinacol coupling, except that after the radical-radical combination step there are two elimination steps and two more electron transfer steps. The intramolecular reaction works well for a wide variety of ring sizes. 

Modem acyloin condensations are usually executed in the presence of MesSiCl, and a bis(silyloxy)alfcene is obtained as the immediate product. The bis(silyl-oxy)alkene may then be hydrolyzed to the acyloin upon workup. The yield of the acyloin condensation is greatly improved under these conditions, especially for intramolecular cyclizations. The MesSiCl may improve the yield by reacting with the ketyl to give a neutral radical, which can undergo radical-radical combination more easily with another ketyl radical due to a lack of electrostatic repulsion. 

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