Dialkylzincs, amino alcohol complexation

Kitamura and Noyori have reported mechanistic studies on the highly diastere-omeric dialkylzinc addition to aryl aldehydes in the presence of (-)-i-exo-(dimethylamino)isoborneol (DAIB) [33]. They stated that DAIB (a chiral (i-amino alcohol) formed a dimeric complex 57 with dialkylzinc. The dimeric complex is not reactive toward aldehydes but a monomeric complex 58, which exists through equilibrium with the dimer 57, reacts with aldehydes via bimetallic complex 59. The initially formed adduct 60 is transformed into tetramer 61 by reaction with either dialkylzinc or aldehydes and regenerates active intermediates. The high enantiomeric excess is attributed to the facial selectivity achieved by clear steric differentiation of complex 59, as shown in Scheme 1.22. 

Since the discovery of amino alcohol induced dialkylzinc addition to aldehydes, many new ligands have been developed. It has recently been reported that chiral amino thiols and amino disulfides can form complexes or structurally strained derivatives with diethylzinc more favorably than chiral amino alcohols and thus enhance the asymmetric induction. Table 2 15 is a brief summary of such chiral catalysts. 

In the (—)-DAIB-catalyzed reaction of diethylzinc and benzaldehyde, the rate is first-order in the amino alcohol. The initial alkylation rate is influenced by the concentration of diethylzinc and benzaldehyde but soon becomes unaffected by increased concentration. Thus, under the standard catalytic reaction conditions, the reaction shows saturation kinetics the rate is zeroth order with respect to both dialkylzinc reagent and aldehyde substrate. These data support the presence of the equilibrium of A-D, and alkyl transfer occurs intramolecularly from the dinuclear mixed-ligand complex D. This is the stereo-determining and also turnover-limiting step. 

The slow nucleophilic addition of dialkylzinc reagents to aldehydes can be accelerated by chiral amino alcohols, producing secondary alcohols of high enantiomeric purity. The catalysis and stereochemistry can be interpreted satisfactorily in terms of a six-membered cyclic transition state assembly [46,47], In the absence of amino alcohol, dialkylzincs and benzaldehyde have weak donor-acceptor-type interactions. When amino alcohol and dialkylzinc are mixed, the zinc atom acts as a Lewis acid and activates the carbonyl of the aldehyde. Zinc in this amino alcohol-zinc complex is regarded as a kind of chirally modified Lewis acid. Various kinds of polymer-supported chiral amino alcohol have recently been prepared and used as ligands in dialkylzinc alkylation of aldehydes. 

Diastereoselective allylation of optically pure suilinyl dienal complexes using tributyl allyltin can be obtained (Scheme 138). 2,4-Hexadien-l,6-dial iron tricarbonyl complex (88) undergoes nucleophilic addition reactions with dialkylzincs in the presence of a catalytic amount of an optically active amino alcohol (Scheme 139). Very high enantio-and diastereoselectivity is observed. Related reactions of (88) with chiral allyl boronic esters give allylated alcohols in very high enantiomeric excess. 

Nucleophilic addition of dialkylzincs (ZnMe2, ZnEt2, ZNBuj, etc.) to aldehydes in the presence of sterically constrained chiral amino alcohols such as 3-exo-(dimethylamino) isoborneol (114) is catalytic and highly enantioselective, giving secondary alcohols in up to 99% ee. These enantioselective alkylations are proposed to proceed via a series of dinuclear zinc complexes of the type (115) and (116), the chirality of whose transfer to... 

V,7V-Dialkyl derivatives of 1 have been successfully applied to the asymmetric addition of dialkylzinc reagents to aldehydes, giving products of moderate enantiomeric excess.In addition, ruthenium(II) complexes of 1 have been demonstrated to be excellent catalysts for the control of the enantioselective transfer hydrogenation of ketones to alcohols at catalyst loadings as low as 1 mol The ruthenium/1 complex has been applied to a range of ketone substrates, including cyclic enones and a-amino and alkoxy substituted derivatives. 

A series of C(2) symmetrical 1 2 Ni/ligand complexes derived from a-amino amides have been studied for the enantioselective addition of dialkylzinc reagents to aldehydes. Different structural elements on the ligands seem to play an important role in determining the observed enantioselectivity. Through optimization of structure and reaction conditions, the best ligand (33) provided secondary alcohols in excellent yields and enantioselectivity of up to 99% ee for the (i )-enantiomer. A transition state model has been proposed to explain the observed enantioselectivities based on computational calculations at the DFT level. 

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