Huang Shuai, Tong Fei-Fei, Bai Da-Chang, Zhang Gao-Peng, Jiang Yang-Jie, Zhang Bo, Leng Xuebing, Guo Ying-Long, Wan Xiao-Long, Zhang Xingang, Ding Chang-Hua, Hou Xue-Long
State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry (SIOC), Chinese Academy of Sciences (CAS), Shanghai, China.
Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, SIOC, CAS, Shanghai, China.
Nat Commun. 2021 Nov 12;12(1):6551. doi: 10.1038/s41467-021-26667-0.
The enantioselective construction of C-CFR (R: alkyl or fluoroalkyl) bonds has attracted the attention of synthetic chemists because of the importance of chiral fluorinated compounds in life and materials sciences. Catalytic asymmetric fluoroalkylation has mainly been realized under organocatalysis and Lewis acid catalysis, with substrates limited to carbonyl compounds. Few examples using transition-metal catalysis exist, owing to side reactions including decomposition and isomerization of fluoroalkylating reagents. Herein we report umpolung asymmetric difluoroallylation of hydrazones with 3-bromo-3,3-difluoropropene (BDFP) under palladium catalysis. Difluoroallylation products having quaternary chiral carbon centers are afforded in good yields with high α/γ- and enantioselectivities. The usefulness of the reaction products is demonstrated and an inner-sphere mechanism of the reaction is proposed. The use of chiral N-heterocyclic carbene as ligand is the key for the selectivities as well as the productivity of the reaction.
由于手性氟化化合物在生命科学和材料科学中的重要性，C-CFR（R：烷基或氟烷基）键的对映选择性构建引起了合成化学家的关注。催化不对称氟烷基化主要在有机催化和路易斯酸催化下实现，底物仅限于羰基化合物。由于包括氟烷基化试剂分解和异构化在内的副反应，使用过渡金属催化的例子很少。在此，我们报道了在钯催化下，腙与3-溴-3,3-二氟丙烯（BDFP）进行的极性反转不对称二氟烯丙基化反应。具有季碳手性中心的二氟烯丙基化产物以良好的产率、高α/γ选择性和对映选择性得到。证明了反应产物的实用性，并提出了反应的内球机理。使用手性N-杂环卡宾作为配体是反应选择性和产率的关键。
