Efficient oxidative resolution of a P-stereogenic triarylphosphine and asymmetric synthesis of a P-stereogenic atropoisomeric biphenyl diphosphine dioxide

• DOI: 10.1016/j.tetasy.2010.06.014
• Publication Date: 2010-07-03T04:23:56Z
• Authors: Kamil Dziuba; Anna Flis; Anna Szmigielska; K. Michał Pietrus...
• Keywords: Enantiopure drug; Stereocenter; Phenylphosphine; Chirality; Biphenyl; Diastereomer; Axial Chirality

Abstract Racemic 3-methoxyphenyl(1-naphthyl)phenylphosphine 1 was effectively resolved via an oxidative resolution procedure utilizing l -menthyl bromoacetate as the resolving agent to give enantiopure 3-methoxyphenyl(1-naphthyl)phenylphosphine oxide ( R )- 2 in 41% yield. Reduction of the resolved ( R )- 4 with HSiCl 3 /NEt 3 provided the corresponding phosphine ( R )- 1 in >97% ee. Ortho -iodination of the enantiopure ( R )- 4 followed by Ullmann coupling of the resulting iodoarylphosphine oxide gave a P -stereogenic and atropoisomeric biphenyl diphosphine dioxide as a single diastereoisomer. The latter transformation constitutes the first example of an effective transfer of a P -centered chirality to an axial chirality of the atropoisomeric biaryl system. The absolute configurations of the resolved phosphine and the atropoisomeric biaryl system have also been established.