Zinc catalysts direct catalytic asymmetric aldol

The catalytic asymmetric aldol reaction is one of the most powerful and efficient asymmetric carbon-carbon bond-forming reactions. The direct catalytic asymmetric aldol reaction, in which unmodified ketones are used as substrates, is the ideal form of this reaction in terms of atom economy.[1] A first generation zinc catalyst, prepared from diethyl zinc/linkcd-BINOL2 2/1 (Figure 11.1), efficiently... 

SCHEME 8.41. Trost and Ito s direct catalytic asymmetric aldol reaction using zinc catalyst. 

Recently, novel bifunctionalized zinc catalysts have been developed (compounds (N) and (P), Scheme 55). They have both Lewis-acid and Lewis-base centers in their complexes, and show remarkable catalytic activity in direct aldol reactions.233-236 A Zn11 chiral diamine complex effectively catalyzes Mannich-type reactions of acylhydrazones in aqueous media to afford the corresponding adducts in high yields and selectivities (Scheme 56).237 This is the first example of catalytic asymmetric Mannich-type reactions in aqueous media, and it is remarkable that this chiral Zn11 complex is stable in aqueous media. 

Other chiral zinc based Lewis acid, such as zinc(II) complex with pybox, showed good stability in aqueous media and gave syn-adducts in moderate to excellent catalytic activity and enantioselectivity for asymmetric Mukaiyama aldol reactions (113,114). A simple combination of Lewis acidic zinc salt (Zn(OTf)2) and organocatalyst is also shown to be effective catalysts for the direct aldol reaction of acetone and aldehydes in the presence of water (115). 

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