Metal alkoxide catalysis of catecholborane and borane reductions. Mechanistic studies

Asymmetric Reduction of Ketones with Catecholborane Using 2,6-BODOL Complexes of Titanium(IV) as Catalysts

“…Firstly, [Ti(OiPr) 4 ] was added to a solution of the ligand in tBuOMe, that contained the molecular sieves, followed by stirring at 45 8C for 1.5 h. During this time we believe that ligand exchange takes place to generate the catalyst, the structure of which is not known at present (see below). Subsequently, the ketone was added followed by a waiting time of 30 min to allow for the formation of a complex with the chiral Lewis acid.…”

“…Such a minor effect of the molecular sieves has also been observed in Diels ± Alder reactions with [(iPrO) 2 TiCl 2 ]/TADDOL as the catalyst. [16] We believe that the molecular sieves only act as a drying agent before the addition of [Ti(OiPr) 4 ].…”

“…[3] Systems that employ Ti IV -based Lewis acids for reductions with boranes have not been investigated to the same degree. In 1994, Lindsley et al showed that the addition of [Ti(OiPr) 4 ] accelerated the reduction of ketones with several boranes. [4] In their investigation, a Ti-TADDOLate (1: TADDOL a,a,a',a'-tetraaryl-1,3-dioxolane-4,5-dimethanol) produced a low ee (24 %) in the catalytic asymmetric reduction of acetophenone.…”

“…In 1994, Lindsley et al showed that the addition of [Ti(OiPr) 4 ] accelerated the reduction of ketones with several boranes. [4] In their investigation, a Ti-TADDOLate (1: TADDOL a,a,a',a'-tetraaryl-1,3-dioxolane-4,5-dimethanol) produced a low ee (24 %) in the catalytic asymmetric reduction of acetophenone. Shortly thereafter, Giffels et al tested several ligands together with [Ti(OiPr) 4 ]; this lead to increased enantioselectivities.…”

“…[11] Several other methyl ketones were successfully reduced with high yields and ees. At the time it seemed necessary to apply rigorous reaction conditions in terms of dryness and quality for all of the reagents (it seemed crucial to distill the [Ti(OiPr) 4 ], as well as the ketones and solvents before use). Moreover, the use of large amounts of molecular sieves seemed necessary to achieve the best results.…”