TADDOL dialkylzinc addition

Seebach and coworkers have developed enantioselective conjugate additions of primary dialkylzinc reagents to 2-aryl- and 2-heteroaryl-nitroalkenes mediated by titanium-TADDO-Lates (Eq. 4.90). x a TADDOLs and their derivatives are excellent chiral auxiliaries.9611... 

Lewis acid-promoted asymmetric addition of dialkylzincs to aldehydes is also an acceptable procedure for the preparation of chiral secondary alcohol. Various chiral titanium complexes are highly enantioselective catalysts [4]. C2-Symmet-ric disulfonamide, chiral diol (TADDOL) derived from tartaric acid, and chiral thiophosphoramidate are efficient chiral ligands. C2-Symmetric chiral diol 10, readily prepared from 1-indene by Brown s asymmetric hydroboration, is also a good chiral source (Scheme 2) [17], Even a simple a-hydroxycarboxylic acid 11 can achieve a good enantioselectivity [18]. 

Enantioselective carbonyl addition of dialkylzinc reagents to aldehydes is one of the most important and fundamental asymmetric reactions [2,15]. Several chiral titanium complexes have been developed to accelerate this type of reaction (Sch. 3) [16,18-26] since Ohno and Kobayashi achieved high enantioselectivity in the presence of Ti(OPr )4 and chiral disulfonylamide [16,17]. Seebach has also demonstrated that TADDOL-derived titanium complexes function as efficient asymmetric catalysts [18]. 

This approach has been extended to the conjugate addition of primary dialkylzincs to 2-aryl- and 2-heteroaryl-nitroolefins to obtain enantioenriched 2-arylamines. Dendritic styryl TADDOLs and polymer-bound Ti-TADDOLates have proved to be very practical chiral catalysts for the enantioselective addition of organozinc to aldehydes. Likewise, the immobilization of BfNOL by a cross-linking copolymerization of styryl derivatives has allowed several enantioselective Ti- and Al-Lewis acid-mediated additions to aldehydes. Dialkylzines obtained via an 1/Zn exchange or a B/Zn exchange have also been successfully used for the enantioselective additions to... 

The enantioselective addition of dialkylzinc reagents to aldehydes is not limited to the homonuclear zinc complexes described above. Seebach has shown that Ti-TADDOL complexes can be effective catalysts for the preparation of a wide range of secondary alcohols (Equation 16) [102], The addition of Et2Zn to aldehydes is carried out with catalyst 165 in combination with 1.2 equiv Ti(Oi-Pr)4 to furnish products in 82-99% ee [17. 103). The use of excess Ti(Oi-Pr)4 is noteworthy, as it is of mechanistic significance. Catalyst turnover is only observed in this system because of the ability of the Ti(Oi-Pr)4 to serve as a reservoir for the alkoxide product. It is remarkable, however, that the presence of excess Ti(Oi-Pr)4 does not lead to any diminution in the enantioselectivity of the product formed. This represents a dramatic example of ligand-accelerated catalysis in C-C bond-forming reactions. 

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