Keto lactones, enantioselective hydrogenation

There are many classes of substrate structures involved in heterogeneous enantioselective hydrogenation on modified metal catalysts. They consist of 2-oxocarboxylic acids and their esters, ketones, diketones, keto lactones, imsaturated acids, oximes, and amides. Enantioselectivities of heterogeneous chirally modified metal catalysts are determined in an important way by the matched interactions between die functional groups of the substrate and the modifier. 

The hydrogenation of ketones with O or N functions in the a- or / -position is accomplished by several rhodium compounds [46 a, b, e, g, i, j, m, 56], Many of these examples have been applied in the synthesis of biologically active chiral products [59]. One of the first examples was the asymmetric synthesis of pantothenic acid, a member of the B complex vitamins and an important constituent of coenzyme A. Ojima et al. first described this synthesis in 1978, the most significant step being the enantioselective reduction of a cyclic a-keto ester, dihydro-4,4-dimethyl-2,3-furandione, to D-(-)-pantoyl lactone. A rhodium complex derived from [RhCl(COD)]2 and the chiral pyrrolidino diphosphine, (2S,4S)-N-tert-butoxy-carbonyl-4-diphenylphosphino-2-diphenylphosphinomethyl-pyrrolidine ((S, S) -... 

A BINAP-Ru catalyzed asymmetric hydrogenation ofy-keto esters and o-acylbenzoic esters gives y-lactones and o-phthalides, respectively, with an excellent enantioselectivity (Scheme 1.36) [190,191], The sense of enantioselection is the same as that in the hydrogenation of a-and (3-keto esters. 

If the reactivity of the substrate in the shielded [substrate-modifier] complexes is higher than that of the free keto ester, enantioselectivity can occur. According to Margitfalvi the quinuclidine N, which aims towards the keto carbonyl group in the keto ester, provides the increased reactivity of the keto carbonyl group. This shielding model, can e q)lain enantioselectivity and rate acceleration effects for almost all substrates used in many examples, for example, hydrogenation of MePy, MBf, ketopanto-lactone, and trifluoroacetophenone over Pt-alumina-Cnd catalysts. 

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