Design of P‑Chirogenic Aminophosphine–Phosphinite Ligands at Both Phosphorus Centers: Origin of Enantioselectivities in Pd-Catalyzed Allylic Reactions

We
have recently patented an unprecedented stereospecific N →
O phosphinyl migration process which transforms P-chirogenic aminophosphines
into phosphinites. A fine design of aminophosphine phosphinite ligands
(AMPP*) derived from ephedrine and bearing a P-chirogenic center either
at the aminophosphine or phosphinite moiety was performed. The synthesis
of AMPP* ligands with a P-chirogenic aminophosphine moiety was based
on the well-established stereospecific reaction of oxazaphospholidine
borane with organolithium reagents, followed by trapping with a chlorophosphine
and borane decomplexation. Concurrently, the preparation of AMPP*
ligands with a P-chirogenic phosphinite moiety was performed by N
→ O phosphinyl migration of aminophosphines borane by heating
at 50 °C with DABCO and then reaction with chlorophosphines.
AMPP* ligands were studied in palladium-catalyzed asymmetric allylic
alkylations, leading to enantioselectivities from 91% (R) to 95% ee (S). X-ray crystallographic data for
relevant Pd–AMPP* complexes and computer modeling explained
the origin of the enantioselectivities based on MO interactions of
most stable conformers with nucleophiles.