Palladium-Catalyzed Asymmetric Phosphination:  Enantioselective Synthesis of a P-Chirogenic Phosphine

Abstract

Chiral phosphines, valuable ligands for metal-catalyzed asymmetric reactions, 1 are usually prepared either by resolution or by using a stoichiometric amount of a chiral auxiliary. 2 Surprisingly, metal-catalyzed asymmetric syntheses of these ligands are rare. 3 We report here that Pd-catalyzed asymmetric phosphination (crosscoupling of a secondary phosphine PH(R)(R′) with an aryl halide or triflate) 4 can be used to prepare a P-chirogenic phosphine with control of stereochemistry at phosphorus. Observations of potential intermediates in the catalytic cycle suggest that dynamic resolution of rapidly inverting phosphorus stereocenters is responsible for the enantiomeric excess (ee)

Advances in Stereoconvergent Catalysis from 2005 to 2015: Transition-Metal-Mediated Stereoablative Reactions, Dynamic Kinetic Resolutions, and Dynamic Kinetic Asymmetric Transformations

“…227,228 Since then, this field has evolved substantially and reviewed in the recent literature. 229,230 As such, only a couple of representative examples will be discussed here.…”

Preparation of phosphines through C–P bond formation

“…The enantioenriched phosphine 108 was obtained through coupling of racemic bulky secondary phosphine 107 with PhI in the presence of the base NaOSiMe 3 and the Pd-catalyst (Scheme 30) [201]. In the following years, the scope and mechanism were elaborated [202–204].…”

Synthesis of Chiral Heterocyclic Phosphines for Application in Asymmetric Catalysis

“…With a Pd(i-Pr-DuPHOS) catalyst asymmetric nucleophilic substitution with benzylic substrates was investigated (up to 90 %ee) [104]. MeDuPHOS was likewise applied as chiral ligand in the Pdcatalyzed asymmetric phosphination (38-78 %ee) [105]. In the addition of Et 2 Zn to N-diphenylphosphinoylimines good enantioselectivities (85-96 %ee) have been obtained with a Cu(II)-catalyst based on Me-DuPHOS [106].…”