Hexafluoroisopropanol for the Selective Deactivation of Poisonous Nucleophiles Enabling Catalytic Asymmetric Cyclopropanation of Complex Molecules
Hexafluoroisopropanol for the Selective Deactivation of Poisonous Nucleophiles Enabling Catalytic Asymmetric Cyclopropanation of Complex Molecules
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DOI：
10.1021/acscatal.2c03909
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发表时间：
2022-09-30
期刊：
影响因子：
12.9
通讯作者：
Davies, Huw M. L.
中科院分区：
文献类型：
--
作者：
Sharland, Jack C.;Dunstan, David;Davies, Huw M. L.
在1，1，1，3，3，3-六氟异丙醇（HFIP）的存在下，防止亲核试剂和反应性试剂与铑卡宾相互作用，从而允许在各种化合物上以高产率和立体选择性发生不对称环丙烷化。在90种不同的有毒亲核试剂和不同量的HFIP（10当量，用作反应溶剂）存在下，用互补催化体系对环丙烷化进行高通量筛选。该研究拓展了重氮乙酸芳基/杂芳基酯和烯烃的应用范围，并最终实现了包括API和天然产物在内的复杂分子的对映体选择性功能化。
In the presence of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), nucleophilic and reactive reagents are prevented from interacting with a rhodium carbene, allowing asymmetric cyclopropanation to occur with high yield and stereoselectivity on a variety of compounds. A high-throughput screen was conducted on cyclopropanation with a complementary catalytic system in the presence of 90 different poisonous nucleophiles and varying amounts of HFIP (10 equiv, used as reaction solvent). The scope of both the aryl/heteroaryl diazoacetate and the olefin was expanded, and the study culminated in the enantioselective functionalization of complex molecules including API and natural products.