Zr-Catalyzed Enantioselective Mannich Reactions

Scheme 6.27. Zr-catalyzed enantioselective Mannich reactions when more electron-withdrawing chiral ligands are used, enantioselectivity and reactivity levels are enhanced. Deprotection is carried out in two steps.

Scheme 6.28. Zr-catalyzed enantioselective Mannich reactions of functionalized ketene acetals deliver high enantio- and diastereoselectivity.

Scheme 6.31. Representative examples of non-Zr-catalyzed enantioselective Mannich reactions.

Scheme 6.29. Zr-catalyzed enantioselective Mannich reactions with chiral 2,2 -Br2(binol) proceed with a higher level of enantioselectivity in the presence of water.

Kobayashi and his team have utilized a catalytic system similar to that used in their development of a Zr-catalyzed Mannich reaction (Schemes 6.27—6.29) to develop a related cycloaddition process involving the same imine substrates as used previously (Scheme 6.35) [105]. As the representative examples in Scheme 6.35 demonstrate, good yields and enantioselectivities (up to 90% ee) are achieved. Both a less substituted version of the Danishefsky diene (—> 110) and those that bear an additional Me group (e. g.— 111) can be utilized. Also as before, these workers propose complex 89, bearing two binol units, to be the active catalytic species. 

The studies summarized above clearly bear testimony to the significance of Zr-based chiral catalysts in the important field of catalytic asymmetric synthesis. Chiral zircono-cenes promote unique reactions such as enantioselective alkene alkylations, processes that are not effectively catalyzed by any other chiral catalyst class. More recently, since about 1996, an impressive body of work has appeared that involves non-metallocene Zr catalysts. These chiral complexes are readily prepared (often in situ), easily modified, and effect a wide range of enantioselective C—C bond-forming reactions in an efficient manner (e. g. imine alkylations, Mannich reactions, aldol additions). 

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