Substrate and Catalyst Screening in Platinum-Catalyzed Asymmetric Alkylation of Bis(secondary) Phosphines. Synthesis of an Enantiomerically Pure C2-Symmetric Diphosphine

Abstract

Platinum-catalyzed asymmetric alkylation of bis(secondary) phosphines was investigated. The modular design of the catalyst precursor Pt(diphos*)(R′)(Cl) and the substrates, a bis(secondary) phosphine HRP∼PHR and a benzyl halide, along with an efficient 31P NMR screening method, enabled rapid evaluation of the rate and diastereoselectivity of these reactions. These experiments identified a selective catalyst, Pt(DuPhos)(Ph)(Cl), and showed that the alkylation of PhHP(CH2)3PHPh (2) was faster and more selective than that of PhHP(CH2)2PHPh (1), MesHP(CH2)3PHMes (3), or 1,1′-(C5H4PHPh)2Fe (4). Alkylation of 1 with o-CF3C6H4CH2Br using the base NaOSiMe3 and the catalyst precursor Pt((R,R)-i-Pr-DuPhos)(Ph)(Cl), or the analogous Me-DuPhos complex, gave the diphosphine Ph(CH2o-CF3C6H4)P(CH2)2P(CH2o-CF3C6H4)Ph (7), which was prepared on a multigram scale and isolated as a borane adduct (6). The rac and meso diastereomers of 6 were separated by recrystallization, and enantiomerically pure 6 was isolated. Both (R,R)- and (S,S)-6, prepared separately in high ee using appropriate catalyst precursors, were characterized by X-ray crystallography, as was meso-7. Separate treatment of (S,S)-7 and meso-7 with Pt(COD)(Ph)(Cl) gave the complexes Pt((S,S)-7)(Ph)(Cl) ((S,S)-8) and Pt(meso-7)(Ph)(Cl) (meso-8). Both diastereomers of 8 were catalyst precursors for synthesis of 7 by alkylation of 1 with o-CF3C6H4CH2Br, but these reactions were unselective, because ligand 7 was rapidly displaced from its complex, 8.