Pinacol coupling reactions with ketones

Titanium-mediated pinacol coupling reactions have been reviewed until 2000.80 81 Since then, various intermole-cular pinacol couplings have been reported with aldehydes, - ketones, a-ketoesters, and imines, as well as asymmetric versions thereof.101-104 Scheme 29 shows one example of an asymmetric pinacol coupling of aromatic aldehydes, promoted and catalyzed by the new chiral titanium complex (A)-75, that has been developed by Riant and co-workers.101 Yields for pinacol products 76 are generally high. Under catalytic conditions, ee is moderate (up to 63%), while stoichiometric conditions allow to obtain up to 91% ee. 

Some additives accelerate the pinacol coupling reactions. Addition of Me3SiCl to Sml2 also accelerates the pinacol coupling reactions of aliphatic ketones and aldehydes. Pinacol coupling reactions are also promoted with samarium metal and a Lewis acid such as Et2AlCl or MesSiCl. Coordination of such a Lewis acid to a carbonyl oxygen facilitates the one-electron reduction by samarium. 

Related to the intramolecular pinacolic coupling reactions in some respects is a ketone-nitrile reductive coupling process. This process also permits the construction of highly functionalized carbocycles, although the yields are sranewhat reduced owing to the reluctance of nitriles to undergo such radical addition reactions (equation 75). Presumably, simple reduction of the ketone to the alcohol c< npetes with the desired process. 

Reichwein, J. F., Pagenkopf, B. L. New Mixed Phosphonate Esters by Transesterification of Pinacol Phosphonates and Their Use in Aldehyde and Ketone Coupling Reactions with Nonstabilized Phosphonates. J. Org. Chem. 2003, 68,1459-1463. 

From a synthetic standpoint the intermolecular pinacolic coupling reaction is limited because only homocoupling reactions are generally practical. Cross-coupling reactions mediated by SmF are restricted to specialized, matched partners [35]. Thus a-dicarbonyl compounds can be heterocoupled with aldehydes, providing facile entry to 2,3-dihydroxy ketones. Although selectivities vary, in some cases the diastereoselectivity of the process can be quite high (Eq. 25). 

The pinacol coupling reaction can be applied to most ketones and aldehydes when two identical molecules are being coupled. An improvement in the reaction involves trapping the initial coupling product as the bis(trimethylsilyl) derivative. Coupling of 4 -methylacetophenone (250) with zinc in the presence of chlorotri-methylsilane gave 76% of the bis-O-silylether, 251.200 Treatment with tetrabutylammonium fluoride removed... 

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