Insight into the Mechanism of the Asymmetric Addition of Alkyl Groups to Aldehydes Catalyzed by Titanium−BINOLate Species

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Abstract
The asymmetric addition of alkyl groups to aldehydes catalyzed by BINOLate−titanium complexes has become the testing grounds to evaluate the potential of new BINOL-based ligands. We have investigated the mechanism of this reaction and report our findings here. Model systems for the open form of the catalyst, (BINOLate)[Ti(O-i-Pr)3]2, based on mono-oxygen-alkylated BINOL ligands have been examined. Comparison of the reactivity and enantioselectivity of the mono-alkyl BINOL derivatives with those of BINOL indicate that the open form of the catalyst, (BINOLate)[Ti(O-i-Pr)3]2, is not active in the asymmetric addition reaction. Several BINOLate−titanium complexes have been synthesized and characterized by X-ray crystallography. These include the dinuclear (BINOLate)Ti(O-i-Pr)2·Ti(O-i-Pr)4, which contains a bridging naphtholate and isopropoxy group, trinuclear (BINOLate)Ti(O-i-Pr)2·[Ti(O-i-Pr)4]2, and trimeric [(BINOL)Ti(O-i-Pr)2]3. The solid-state and solution structures reported here indicate that (BINOLate)Ti(O-i-Pr)2 prefers to bind to titanium tetraisopropoxide rather than to itself, explaining why no nonlinear effects are observed in the catalytic reaction. Additionally, experimental evidence suggests that the BINOLate−titanium species responsible for the catalytic and stoichiometric asymmetric addition reactions are different, indicating that the proposed intermediate, (BINOLate)Ti(R)(aldehyde)(O-i-Pr), is not involved in either of these processes. Reactions were examined using different sources of the alkyl group [ZnMe2 or MeTi(O-i-Pr)3]. Under similar conditions, it was found that the product ee's were the same, independent of whether ZnMe2 or Me-Ti(O-i-Pr)3 was used as the source of the alkyl groups. This indicates that the role of the dialkylzinc is not to add the alkyl group to the carbonyl but rather to transfer the alkyl group to titanium. On the basis of these results, we hypothesize that the intermediate in the asymmetric addition involves (BINOLate)Ti(O-i-Pr)2(aldehyde)·MeTi(O-i-Pr)3.
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