Metal-Catalyzed Asymmetric Synthesis of P-Stereogenic Phosphines

Abstract

This account summarizes our attempts to develop metalcatalyzed asymmetric syntheses of P-stereogenic phosphines. While such phosphines undergo pyramidal inversion slowly at room temperature, inversion is rapid in metal-phosphido complexes (M-PR 2 ). These observations were the basis for catalytic, dynamic kinetic resolution processes in which racemic secondary phosphines [PR(R¢)H] were converted into enantioenriched tertiary phosphines [PR(R¢)(R¢¢)] by platinum-catalyzed asymmetric hydrophosphination of acrylonitrile or related Michael acceptors, by palladium-catalyzed asymmetric phosphination of aryl iodides using secondary phosphines or phosphine-boranes, and by platinumcatalyzed asymmetric alkylation of secondary phosphines. The key intermediates were diastereomeric phosphido complexes with chiral ancillary ligands (L n *-M-PRR¢). Their relative rates of P-inversion and phosphorus-carbon bond formation controlled the enantioselectivity of product formation, whether the phosphoruscarbon bonds were formed by reductive elimination (for Pd), or by the reaction of a platinum-phosphido complex with an electrophile (an alkene in hydrophosphination, or a benzyl bromide in alkylation). The results of mechanistic studies and their use in the design of improved catalytic reactions are described.

Recent Advances in Metal-Catalyzed C–P Bond Formation

“…Recently, chiral metal catalysts have been used in enantioselective phosphination, yielding P-stereogenic phosphines [72][73][74]. In the first such example, asymmetric phosphination was catalyzed by Pd(DuPhos) complexes.…”

Density functional analysis of group 10 organometallic diphosphinito complexes for catalytic formation of C‐P bonds

“…Recent and ongoing demands for novel biochemical and pharmaceutical compounds have created interest in increasingly efficient methods for forming carbon–phosphorous (C‐P) bonds . Specifically, the interest in stereospecific C‐P bond formation in chiral compounds has motivated investigation of new catalytic synthetic approaches …”

“…[1][2][3] Specifically, the interest in stereospecific C-P bond formation in chiral compounds has motivated investigation of new catalytic synthetic approaches. [4][5][6][7][8][9][10][11][12][13] Hydrophosphination of unsaturated organic compounds is an atomically efficient method for synthesizing carbon-phosphorous bonds in organic synthesis. Thus, stereospecific production of C-P bonds in chiral complexes can proceed with minimal wasted material through the hydrophosphination process.…”

Synthesis, structure, and reactivity of platinum compounds featuring terminal amido and phosphido ligands

“…The number of terminal amido or anilido complexes of platinum has been somewhat limited [26,27], and theories to understand the relative stabilities of these and related systems have emerged [28,29]. Extensive study of hydrophosphination chemistry by Glueck and coworkers has been a major driving force in the preparation of platinum compounds with terminal phosphido ligands [30][31][32][33][34][35][36]. However, compounds that possess sufficiently encumbered substituents to support three-coordinate platinum are required to enact the proposed synthetic strategy because bridging of these nucleophilic ligands is assumed to be an effectively irreversible process.…”