Catalyst structural effects in titanocene-catalyzed pinacol coupling: activity, stereoselectivity and mechanistic implications

The effects of catalyst structural variation on the activity and selectivity of titanocene-catalyzed pinacol coupling of cyclohexane carboxaldehyde by Mn/TMSCl have been evaluated. Complexes which have been tested include: Cp2TiCl2 (1), Cp2TiBr2 (2), (C5Me5)2TiCl2 (3), (1,3-t-Bu2C5H3)2TiCl2 (4), (1,3-t-Bu2C5H3)(Cp)TiCl2 (5), ansa-[(η5-tetrahydroindenyl)CH2CH2(η5-tetrahydroindenyl)]TiCl2 (6), and ansa-[(η5-Cp)CH2CH2(η5-fluorenyl)]TiCl2 (7). Cp2TiCl2 (1) is the most active (pre)catalyst for pinacol silylether (8a) formation, but Brintzingerʹs complex 6 provides the best dl/meso diastereoselectivity (5:1). Complexes 2, 4 and 7 slowly catalyze the predominant formation of the corresponding pinacol acetal 9a as a secondary product. Comparative stoichiometric reactions of benzaldehyde/Me3SiCl with [Cp2TiCl·MnCl2(THF)2·Cp2TiCl] (10) and [Cp2TiCl]2 (11) result in highly diastereoselective pinacol silylether formation with binuclear 11 (29:1), but primarily the production of pinacol acetal (9b) from trimetallic 10, suggesting a dominant role for the binuclear complex (or derived mononuclear species) in the catalytic systems employing Cp2TiCl2/M/TMSCl, contrary to previous suggestions.