Platinum-Catalyzed Asymmetric Alkylation of Bis(isitylphosphino)ethane: Stereoselectivity Reversal in Successive Formation of Two P−C Bonds

Alkylation of the bis(secondary) phosphine IsHP(CH2)2PHIs (1; Is = isityl = 2,4,6-(i-Pr)3C6H2) with 2-(bromomethyl)naphthalene using 10 mol % of the catalyst precursor Pt((R,R)-Me-DuPhos)(Ph)(Cl) and the base NaOSiMe3 selectively yielded meso-IsP(CH2Ar)(CH2)2P(CH2Ar)(Is) (2; Ar = 2-naphthyl; dr = meso/rac ratio = 3.4:1). Half-alkylated IsP(CH2Ar)(CH2)2PH(Is) (3), an intermediate in this reaction, was prepared from 1 by deprotonation (s-BuLi) and alkylation with 2-(chloromethyl)naphthalene. Analysis of the observed diastereo- and enantioselectivity in the Pt-catalyzed alkylations of 1 and 3 yielded quantitative information on the stereoselectivity of both P−C bond-forming steps. The first alkylation (1 → 3) resulted in diastereoselective formation of a tertiary phosphine stereocenter (∼2:1 ratio). In the second alkylation (3 → 2), however, both (RP)-3 and (SP)-3 (the label refers to the configuration of the tertiary phosphine) selectively formed meso-2, instead of (R,R)-2 or (S,S)-2, respectively (the ratios were ca. 3:1 and 7:1). Thus, the tertiary phosphine in 3 favored alternation of stereochemistry in the alkylation of the secondary phosphine (substrate control with negative cooperativity). Platinum-catalyzed alkylation of IsPH(CH2)2OSi(i-Pr)3 (6) gave IsP(CH2Ar)(CH2)2OSi(i-Pr)3 (9) in a 1.5:1 enantiomeric ratio (er). A related reaction of IsPH(CH2)2OSiMe3 (4) gave a mixture of IsP(CH2Ar)(CH2)2OR (R = SiMe3 (7); R = H (8)), while alkylation of IsPH(CH2)2OH (5) gave 8 in about 2:1 er. Thus, the nature, and even the absolute configuration, of the pendant group X three bonds from the reactive phosphorus center in the substrates IsHP(CH2)2X (X = PHIs (1), P(CH2Ar)(Is) (3), OSiMe3 (4), OH (5), OSi(i-Pr)3 (6)) had a strong influence on the selectivity of Pt-catalyzed phosphorus alkylation. Possible mechanistic explanations for this substrate control are discussed.