Stereodivergent S<sub>N</sub>2@P Reactions of Borane
Oxazaphospholidines: Experimental and Theoretical Studies
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Abstract
The
stereodivergent ring-opening of 2-phenyl oxazaphospholidines
with alkyl lithium reagents is reported. N-H oxazaphospholidines derived
from both (+)-<i>cis</i>-1-amino-2-indanol and (−)-norephedrine
provide inversion products in a highly stereoselective process. In
contrast, N-Me oxazaphospholidines yield ring-opening products with
retention of configuration at the P center, as previously reported
by Jugé and co-workers. As a result, from a single amino alcohol
auxiliary, both enantiomers of key P-stereogenic intermediates could
be synthesized. Theoretical studies of ring-opening with model oxazaphospholidines
at the DFT level have elucidated the streochemical course of this
process. N-H substrates react in a single step via preferential backside
S<sub>N</sub>2@P substitution with inversion at phosphorus. N-methylated
substrates react preferentially via a two-step frontside S<sub>N</sub>2@P, yielding a ring-opened product in which the nucleophilic methyl
binds to P with retention of configuration. DFT calculations have
shown that the BH<sub>3</sub> unit is a potent directing group to
which the methyl lithium reagent coordinates via Li in all the reactions
studied