Palladium-Catalyzed Asymmetric Phosphination. Scope, Mechanism, and Origin of Enantioselectivity

Asymmetric cross-coupling of aryl iodides (ArI) with secondary arylphosphines (PHMe(Ar‘), Ar‘
= (2,4,6)-R3C6H2; R = i-Pr (Is), Me (Mes), Ph (Phes)) in the presence of the base NaOSiMe3 and a chiral
Pd catalyst precursor, such as Pd((R,R)-Me-Duphos)(trans-stilbene), gave the tertiary phosphines PMe(Ar‘)(Ar) in enantioenriched form. Sterically demanding secondary phosphine substituents (Ar‘) and aryl
iodides with electron-donating para substituents resulted in the highest enantiomeric excess, up to 88%.
Phosphination of ortho-substituted aryl iodides required a Pd(Et-FerroTANE) catalyst but gave low
enantioselectivity. Observations during catalysis and stoichiometric studies of the individual steps suggested
a mechanism for the cross-coupling of PhI and PHMe(Is) (1) initiated by oxidative addition to Pd(0) yielding
Pd((R,R)-Me-Duphos)(Ph)(I) (3). Reversible displacement of iodide by PHMe(Is) gave the cation [Pd((R,R)-Me-Duphos)(Ph)(PHMe(Is))][I] (4), which was isolated as the triflate salt and crystallographically characterized. Deprotonation of 4-OTf with NaOSiMe3 gave the phosphido complex Pd((R,R)-Me-Duphos)(Ph)(PMeIs)
(5); an equilibrium between its diastereomers was observed by low-temperature NMR spectroscopy.
Reductive elimination of 5 yielded different products depending on the conditions. In the absence of a trap,
the unstable three-coordinate phosphine complex Pd((R,R)-Me-Duphos)(PMeIs(Ph)) (6) was formed.
Decomposition of 5 in the presence of PhI gave PMeIs(Ph) (2) and regenerated 3, while trapping with
phosphine 1 during catalysis gave Pd((R,R)-Me-Duphos)(PHMe(Is))2 (7), which reacted with PhI to give 3.
Deprotonation of 1:1 or 1.4:1 mixtures of cations 4-OTf gave the same 6:1 ratio of enantiomers of PMeIs(Ph) (2), suggesting that the rate of P inversion in 5 was greater than or equal to the rate of reductive
elimination. Kinetic studies of the first-order reductive elimination of 5 were consistent with a Curtin−Hammett−Winstein−Holness (CHWH) scheme, in which pyramidal inversion at the phosphido ligand was
much faster than P−C bond formation. The absolute configuration of the phosphine (SP)-PMeIs(p-MeOC6H4)
was determined crystallographically; NMR studies and comparison to the stable complex 5-Pt were
consistent with an RP-phosphido ligand in the major diastereomer of the intermediate Pd((R,R)-Me-Duphos)(Ph)(PMeIs) (5). Therefore, the favored enantiomer of phosphine 2 appeared to be formed from the major
diastereomer of phosphido intermediate 5, although the minor intermediate diastereomer underwent P−C
bond formation about three times more rapidly. The effects of the diphosphine ligand, the phosphido
substituents, and the aryl group on the ratio of diastereomers of the phosphido intermediates Pd(diphos*)(Ar)(PMeAr‘), their rates of reductive elimination, and the formation of three-coordinate complexes were
probed by low-temperature 31P NMR spectroscopy; the results were also consistent with the CHWH scheme.