Copper-catalyzed enantioselective Sonogashira-type oxidative cross-coupling of unactivated C(sp3)−H bonds with alkynes
Copper-catalyzed enantioselective Sonogashira-type oxidative cross-coupling of unactivated C(sp3)−H bonds with alkynes
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DOI：
10.1038/s41467-019-13705-1
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发表时间：
2019-12
影响因子：
16.6
通讯作者：
Zhenhai Zhang;Xiao-Yang Dong;Xuan-Yi Du;Qiangshuai Gu;Zhong-Liang Li;Xin‐Yuan Liu
中科院分区：
文献类型：
--
作者：
Zhenhai Zhang;Xiao-Yang Dong;Xuan-Yi Du;Qiangshuai Gu;Zhong-Liang Li;Xin‐Yuan Liu
过渡金属催化的对映选择性Sonogashira型氧化C（sp3）-C（sp）未活化C（sp3）−H键与末端炔的偶联仍然是一个突出的挑战。困难主要来自于未活化的C（sp3）-H键功能化的区域控制和末端炔容易发生的Glaser偶联的抑制。在这里，我们报告了一个铜/手性金鸡纳生物碱为基础的N，N，P-配体催化剂的不对称氧化交叉偶联未活化的C（sp3）-H键与末端炔在一个高度区域，化学和对映选择性的方式。使用N-氟酰胺作为温和的氧化剂是必不可少的，以位点选择性地产生烷基自由基物种，同时有效地避免格拉泽homocoupling。该反应可容纳一系列（杂）芳基和烷基炔;（杂）苄基和炔丙基C（sp3）−H键都适用。该方法允许方便地获得手性炔基酰胺/醛。更重要的是，当与后续转化结合时，它还为手性C（sp3）-C（sp）、C（sp3）-C（sp2）和C（sp3）-C（sp3）键的构建提供了通用工具。
Transition metal-catalyzed enantioselective Sonogashira-type oxidative C(sp3)—C(sp) coupling of unactivated C(sp3)−H bonds with terminal alkynes has remained a prominent challenge. The difficulties mainly stem from the regiocontrol in unactivated C(sp3)—H bond functionalization and the inhibition of readily occurring Glaser homocoupling of terminal alkynes. Here, we report a copper/chiral cinchona alkaloid-basedN,N,P-ligand catalyst for asymmetric oxidative cross-coupling of unactivated C(sp3)—H bonds with terminal alkynes in a highly regio-, chemo-, and enantioselective manner. The use ofN-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(sp3)−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(sp3)—C(sp), C(sp3)—C(sp2), and C(sp3)—C(sp3) bonds when allied with follow-up transformations.