Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, School of Chemistry and Chemical Engineering, Linyi University, Linyi, 276005, China.
Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen, 518055, China.
Nat Commun. 2019 Dec 12;10(1):5689. doi: 10.1038/s41467-019-13705-1.
Transition metal-catalyzed enantioselective Sonogashira-type oxidative C(sp)-C(sp) coupling of unactivated C(sp)-H bonds with terminal alkynes has remained a prominent challenge. The difficulties mainly stem from the regiocontrol in unactivated C(sp)-H bond functionalization and the inhibition of readily occurring Glaser homocoupling of terminal alkynes. Here, we report a copper/chiral cinchona alkaloid-based N,N,P-ligand catalyst for asymmetric oxidative cross-coupling of unactivated C(sp)-H bonds with terminal alkynes in a highly regio-, chemo-, and enantioselective manner. The use of N-fluoroamide as a mild oxidant is essential to site-selectively generate alkyl radical species while efficiently avoiding Glaser homocoupling. This reaction accommodates a range of (hetero)aryl and alkyl alkynes; (hetero)benzylic and propargylic C(sp)-H bonds are all applicable. This process allows expedient access to chiral alkynyl amides/aldehydes. More importantly, it also provides a versatile tool for the construction of chiral C(sp)-C(sp), C(sp)-C(sp), and C(sp)-C(sp) bonds when allied with follow-up transformations.
过渡金属催化的非活化 C(sp)-H 键与末端炔烃的对映选择性 Sonogashira 型氧化 C(sp)-C(sp)偶联仍然是一个突出的挑战。这些困难主要源于非活化 C(sp)-H 键功能化的区域控制和末端炔烃易发生的 Glaser 同型偶联的抑制。在这里，我们报告了一种铜/手性金鸡纳生物碱基 N，N，P-配体催化剂，用于非活化 C(sp)-H 键与末端炔烃的不对称氧化交叉偶联，具有高度的区域、化学和对映选择性。使用 N-氟酰胺作为温和氧化剂对于选择性地生成烷基自由基物种是必不可少的，同时有效地避免了 Glaser 同型偶联。该反应可容纳一系列（杂）芳基和烷基炔烃；（杂）苄基和炔丙基 C(sp)-H 键都适用。该过程允许快速获得手性炔基酰胺/醛。更重要的是，当与后续转化结合使用时，它还为构建手性 C(sp)-C(sp)、C(sp)-C(sp)和 C(sp)-C(sp)键提供了一种多功能工具。
