Effects of Linker Length on the Rate and Selectivity of Platinum-Catalyzed Asymmetric Alkylation of the Bis(isitylphosphino)alkanes IsHP(CH2)nPHIs (Is = 2,4,6-(i-Pr)3C6H2, n = 1−5)

Abstract

Catalytic asymmetric alkylation of the bis(secondary phosphines) IsHP(CH2)nPHIs (1a−e, n = 1−5, Is = isityl = 2,4,6-(i-Pr)3C6H2) with benzyl bromide using the base NaOSiMe3 and the catalyst precursor Pt((R,R)-Me-DuPhos)(Ph)(Cl) gave the bis(tertiary phosphines) Is(PhCH2)P(CH2)nP(CH2Ph)Is (2a−e, n = 1−5) via the intermediates Is(PhCH2)P(CH2)nPHIs (4a−e, n = 1−5). The rates of these reactions depended strongly on n, in the order 1a < 1b < 1c ≈ 1d ≈ 1e. The bulkier bis(secondary phosphine) Mes*HP(CH2)2PHMes* (5, Mes* = 2,4,6-(t-Bu)3C6H2) did not undergo catalytic alkylation under these conditions. The alkylation selectivity also depended on n. Alkylation of 1b was meso-selective, while alkylation of 1a,c−e was rac-selective, occurring with similar diastereoselectivity and enantioselectivity for the longer linkers (1c−e). The product ratios suggested that the catalyst controlled the selectivity for 1d,e, while substrate control operated for ethano-bridged 1b, with negative cooperativity. Substrate control als...