Optimized Catalytic Enantioselective Aryl Transfer Process Gives Access to mGlu2 Receptor Potentiators
2007-05-18T00:00:00Z (GMT) by
An asymmetric enantioselective aryl transfer reaction was developed to give access to the diarylmethanol <b>7</b> and ultimately acetate <b>2</b> which is useful for the preparation of mGlu2 receptor potentiators (Scheme ). The aryl transfer chemistry involved the preparation of a proposed arylalkylzinc species <b>14</b> from boroxine <b>16</b> and diethylzinc (DEZ), and reacting this mixture with aldehyde <b>5</b> in the presence of chiral ligand <b>15</b>. During the course of optimizing the preparations of proposed intermediate <b>14</b> and diarylmethanol <b>7</b>, an understanding of optimal stoichiometry and reaction times was gained through empirical observation, the use of solution IR, and analyzing off-gases via real time gas analysis/mass spectroscopy. The preparation of diarylmethanol <b>7</b> and subsequent conversion into acetate <b>2</b> required carefully selected workups, selective extractions, and azeotropic distillations to generate a series of stock solutions to accommodate oil intermediates that finally gave acetate <b>2</b> as a crystalline solid with >99% ee.