Turning regioselectivity into stereoselectivity: efficient dual resolution of P-stereogenic phosphine oxides through bifurcation of the reaction pathway of a common intermediate.
Synthetic routes that provide facile access to either enantiomeric form of a target compound are particularly valuable. The crystallization-free dual resolution of phosphine oxides that gives highly enantioenriched materials (up to 94 % ee) in excellent yields is reported. Both enantiomeric oxides have been prepared from a single intermediate, (RP )-alkoxyphosphonium chloride, which is formed in the course of a selective dynamic kinetic resolution using a single enantiomer of menthol as the chiral auxiliary. The origin of the dual stereoselectivity lies in bifurcation of the reaction pathway of this intermediate, which works as a stereochemical railroad switch. Under controlled conditions, Arbuzov-type collapse of this intermediate proceeds through CO bond fission with retention of the configuration at the phosphorus center. Conversely, alkaline hydrolysis of the PO bond leads to the opposite SP  enantiomer.
Centre for Synthesis and Chemical Biology, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4 (Ireland). kirill.nikitin@ucd.ie.
Kirill
K
Nikitin
Kamalraj V
KV
Rajendran
Helge
H
Müller-Bunz
Declan G
DG
Gilheany
chiral resolution; chirality; enantioselectivity; phosphine oxides; regioselectivity