Enantioselective reduction Lewis acid coordination

The boron atom dominates the reactivity of the boracyclic compounds because of its inherent Lewis acidity. Consequently, there have been very few reports on the reactivity of substituents attached to the ring carbon atoms in the five-membered boronated cyclic systems. Singaram and co-workers developed a novel catalyst 31 based on dicarboxylic acid derivative of 1,3,2-dioxaborolane for the asymmetric reduction of prochiral ketones 32. This catalyst reduces a wide variety of ketones enantioselectively in the presence of a co-reductant such as LiBH4. The mechanism involves the coordination of ketone 32 with the chiral boronate 31 and the conjugation of borohydride with carboxylic acid to furnish the chiral borohydride complex 34. Subsequent transfer of hydride from the least hindered face of the ketone yields the corresponding alcohol 35 in high ee (Scheme 3) <20060PD949>. 

The use of Al(III) complexes as catalysts in Lewis acid mediated reactions has been known for years. However, recent years have witnessed interesting developments in this area with the use of ingeiuously designed neutral tri-coordinate Al(lll) chelates. Representative examples involving such chelates as catalysts include (1) asymmetric acyl halide-aldehyde cyclocondensations, " (2) asymmetric Meerwein-Schmidt-Ponndorf-Verley reduction of prochiral ketones, (3) aldol transfer reactions and (4) asymmetric rearrangement of a-amino aldehydes to access optically active a-hydroxy ketones. It is important to point out that, in most cases, the use of a chelating ligand appears critical for effective catalytic activity and enantioselectivity. 

Chiral oxazaborolidine salts are useful catalysts not only for enantioselective reductions (i.e., CBS reduction), but also for promoting enantioselective D-A reactions. The cationic Lewis acids formed by reaction of chiral oxazaborolidines with triflic acid [TfOH] or trifluoromethanesulfonimide [(Tf)2NH] coordinate to dienophiles to direct subsequent cycloadditions in a highly controlled fashion. The D-A reactions using these chiral salts proceed in CH2CI2 under very mild conditions at temperatures as low as -95 °C (Table 9.4). ... 

A prochiral radical intermediate is generated from a-methoxymethyl-a-iododihy-drocoumarin (la) which is coordinated via the carbonyl oxygen to the chiral Lewis acid/ligand combination of MgL and 2. Enantiomeric excesses of up to 62% and yields of 88% have been obtained in this enantioselective reduction using tributyltin... 

A new catalyst (46) (Figure 5) for asymmetric reduction of ketones with borane gives moderate to good enantioselectivities. It was designed to provide a Lewis basic site (the pyridyl nitrogen atom) in addition to the Lewis acidic site so that coordination of borane would enable intramolecular hydride delivery [structure (48)]. The success of this strategy was confirmed by the inferior enantioselectivity of the analogue (47), which has no Lewis basic site. ... 

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