op0602268_si_001.pdf (161.23 kB)
Optimized Catalytic Enantioselective Aryl Transfer Process Gives Access to mGlu2 Receptor Potentiators
journal contribution
posted on 2007-05-18, 00:00 authored by Nicholas A. Magnus, Peter B. Anzeveno, D. Scott Coffey, David A. Hay, Michael E. Laurila, Jeffrey M. Schkeryantz, Bruce W. Shaw, Michael A. StaszakAn asymmetric enantioselective aryl transfer reaction was
developed to give access to the diarylmethanol 7 and ultimately
acetate 2 which is useful for the preparation of mGlu2 receptor
potentiators (Scheme ). The aryl transfer chemistry involved
the preparation of a proposed arylalkylzinc species 14 from
boroxine 16 and diethylzinc (DEZ), and reacting this mixture
with aldehyde 5 in the presence of chiral ligand 15. During the
course of optimizing the preparations of proposed intermediate
14 and diarylmethanol 7, 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 7 and subsequent conversion into acetate 2
required carefully selected workups, selective extractions, and
azeotropic distillations to generate a series of stock solutions
to accommodate oil intermediates that finally gave acetate 2 as
a crystalline solid with >99% ee.