Dinuclear Tricyclic Transition State Model for Carbonyl Addition of Organotitanium Reagents: DFT Study on the Activity and Enantioselectivity of BINOLate Titanium Catalysts.

In the presence of a catalytic amount of chiral BINOL derivatives (or BINOLs), a mixture of various organometallic compounds with Ti(O i Pr)4 undergoes enantioselective addition to aldehydes and ketones. Although the catalyst and reacting nucleophile of the reaction have been elucidated to be ( BINOLate)Ti2 (O i Pr)6 and RTi(O i Pr)3 , respectively, little is known about the properties of short-lived intermediates and transition structures. In this work, the mechanism of this reaction is investigated with the aid of DFT (M06) calculations. The study provides support for the following mechanistic understandings: (i) The direct racemic reaction proceeds through a pathway involving initial aggregation of RTi(O i Pr)3 with Ti(O i Pr)4 followed by carbonyl addition of the resulting dinuclear aggregate. (ii) The enantioselective reaction takes place through a pathway involving initial ligand exchange of RTi(O i Pr)3 with ( BINOLate)Ti2 (O i Pr)6 followed by the addition of the resulting chiral dinuclear titanium species via a chiral BINOLate-chelated, tricyclic transition structure. (iii) The enantioselective pathway is favorable not because BINOLate ligands accelerate the carbonyl addition but because the ligands stabilize the chiral dinuclear species against deaggregation through a chelating bridge. (iv) The chiral transition structure serves as a model accounting for the re-face addition generally observed in the reaction of aldehydes with ( R)- BINOLs.