Copper(I)-Catalyzed Asymmetric Alkylation of Unsymmetrical Secondary Phosphines

A copper(I)-catalyzed asymmetric alkylation of (HPArAr2)-Ar-1 with alkyl halides is uncovered, which provides an array of P-stereogenic phosphines in generally high yield and enantioselectivity. The electrophilic alkyl halides enjoy a broad substrate scope, including allyl bromides, propargyl bromide, benzyl bromides, and alkyl iodides. Moreover, 11 unsymmetrical diarylphosphines ((HPArAr2)-Ar-1) serve as competent pronucleophiles. The present methodology is also successfully applied to catalytic asymmetric double and triple alkylation, and the corresponding products were obtained in moderate diastereo- and excellent enantioselectivities. Some P-31 NMR experiments indicate that bulky HPPhMes exhibits weak competitively coordinating ability to the Cu(I)-bisphosphine complex, and thus the presence of stoichiometric (HPArAr2)-Ar-1 does not affect the enantioselectivity significantly. Therefore, the high enantioselectivity in this reaction is attributed to the high performance of the unique Cu(I)-(R,RP)-TANIAPHOS complex in asymmetric induction. Finally, one monophosphine and two bisphosphines prepared by the present reaction are employed as efficient chiral ligands to afford three structurally diversified Cu(I) complexes, which demonstrates the synthetic utility of the present methodology.

Automated summary

A copper(I)-catalyzed asymmetric alkylation reaction has been developed, providing an array of P-stereogenic phosphines in high yield and enantioselectivity. This methodology is also applicable to catalytic asymmetric double and triple alkylation reactions, yielding products with moderate diastereo- and excellent enantioselectivities. The high enantioselectivity is attributed to the performance of the unique Cu(I)-(R,RP)-TANIAPHOS complex in asymmetric induction.