CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Centre for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
J Am Chem Soc. 2021 Jul 7;143(26):9912-9921. doi: 10.1021/jacs.1c04112. Epub 2021 Jun 23.
A copper(I)-catalyzed asymmetric alkylation of HPArAr with alkyl halides is uncovered, which provides an array of -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 (HPArAr) 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 NMR experiments indicate that bulky HPPhMes exhibits weak competitively coordinating ability to the Cu(I)-bisphosphine complex, and thus the presence of stoichiometric HPArAr does not affect the enantioselectivity significantly. Therefore, the high enantioselectivity in this reaction is attributed to the high performance of the unique Cu(I)-(,)-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.
一种铜（I）催化的手性膦不对称烷基化反应被揭示，该反应可以高收率和对映选择性地提供一系列 -手性膦配体。亲电的卤代烷烃具有广泛的底物范围，包括烯丙基溴、炔丙基溴、苄基溴和碘代烷烃。此外，11 种不对称二芳基膦（HPArAr）作为有效的亲核试剂。该方法也成功地应用于催化不对称双烷基化和三烷基化反应，得到了中等的非对映选择性和优异的对映选择性产物。一些磷 NMR 实验表明，体积庞大的 HPPhMes 对 Cu（I）-双膦配合物表现出较弱的竞争配位能力，因此，等摩尔量的 HPArAr 不会显著影响对映选择性。因此，该反应的高对映选择性归因于独特的 Cu（I）-（，）-TANIAPHOS 配合物在手性诱导中的高性能。最后，通过本反应制备的一种单膦和两种双膦配体被用作有效的手性配体，得到了三种结构多样化的 Cu（I）配合物，这证明了本方法的合成实用性。
