Effect of Linker Length on Selectivity and Cooperative Reactivity in Platinum-Catalyzed Asymmetric Alkylation of Bis(phenylphosphino)alkanes

• Published in: ACS catalysis Vol. 6; no. 12; pp. 8106 - 8114
• Main Authors: Anderson, Brian J, Reynolds, Samantha C, Guino-o, Marites A, Xu, Zhiming, Glueck, David S
• Format: Journal Article
• Language: English
• Published: American Chemical Society 02.12.2016
• Subjects: substrate control; bifunctional; asymmetric alkylation; C 2-symmetric; cooperativity; catalyst control
• DOI: 10.1021/acscatal.6b03004
• ISSN: 2155-5435

The selectivity of catalytic asymmetric transformations of bifunctional symmetrical substrates often depends on the linker between the two reactive sites. If the catalyst controls the selectivity of reactions at both sites, the rac product will be formed in high enantiomeric ratio (er) via asymmetric amplification. Substrate control may augment this selectivity (positive cooperativity) or detract from it (negative cooperativity). Here, we investigated the effect of linker length on the selectivity of catalytic asymmetric alkylation of the bis­(secondary phosphines) PhHP­(CH2) n PHPh (n = 2–6; 1a–e) with benzyl bromide using the base NaOSiMe3 and the catalyst precursor Pt­((R,R)-Me-DuPhos)­(Ph)­(Cl). These reactions yielded the diastereomerically and enantiomerically enriched bis­(tertiary phosphines) Ph­(PhCH2)­P­(CH2) n P­(CH2Ph)­Ph (n = 2–6, 2a–e). Pt-catalyzed benzylation of the model phosphines PH­(Ph)­((CH2) n H) (n = 2–6; 4a–e) gave enantiomerically enriched P­(CH2Ph)­(Ph)­((CH2) n H) (n = 2–6; 5a–e). The partially alkylated bis­(phosphines) PhHP­(CH2) n P­(CH2Ph)­Ph (n = 2, 3, 5; 3a,b,d) were prepared with different degrees of enantiomeric enrichment at the tertiary phosphine centers and then catalytically alkylated to give 2a,b,d. From the diastereoselectivity and enantioselectivity of the transformations 1 → 2 and 3 → 2, the selectivity of each individual alkylation step (1 → 3R or 3S; 3R → 2RR or 2RS; 3S → 2SS or 2SR) could be determined as a function of linker length and compared to the selectivity of alkylation of the model monophosphines 4. The two alkylations of bis­(secondary phosphines) 1b–e with longer linker lengths (n = 3–6) showed identical selectivity, within experimental error. This catalyst control resulted in asymmetric amplification of rac-2. In contrast, the selectivity of the first alkylation of ethano-bridged 1a was lower than that in 1b–e (negative cooperativity), but the selectivity of the second alkylation (of intermediate 3a) increased due to positive cooperativity. Possible mechanistic explanations for the observed dependence of selectivity on linker length are discussed.