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Turning Regioselectivity into Stereoselectivity: Efficient Dual Resolution of P‐Stereogenic Phosphine Oxides through Bifurcation of the Reaction Pathway of a Common Intermediate
Author(s) -
Nikitin Kirill,
Rajendran Kamalraj V.,
MüllerBunz Helge,
Gilheany Declan G.
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201309556
Subject(s) - stereocenter , stereoselectivity , chemistry , kinetic resolution , regioselectivity , phosphine , enantiomer , thioether , walden inversion , stereochemistry , combinatorial chemistry , medicinal chemistry , organic chemistry , enantioselective synthesis , catalysis
Abstract 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, ( R P )‐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 CO bond fission with retention of the configuration at the phosphorus center. Conversely, alkaline hydrolysis of the PO bond leads to the opposite S P enantiomer.