Kang Tengfei, Hou Liuzhen, Ruan Sai, Cao Weidi, Liu Xiaohua, Feng Xiaoming
Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu, 610064, China.
Nat Commun. 2020 Aug 3;11(1):3869. doi: 10.1038/s41467-020-17681-9.
The investigation of diverse reactivity of β,γ-unsaturated carbonyl compounds is of great value in asymmetric catalytic synthesis. Numerous enantioselective transformations have been well developed with β,γ-unsaturated carbonyl compounds as nucleophiles, however, few example were realized by utilizing them as not only nucleophiles but also electrophiles under a same catalytic system. Here we report a regioselective catalytic asymmetric tandem isomerization/α-Michael addition of β,γ-unsaturated 2-acyl imidazoles in the presence of chiral N,N'-dioxide metal complexes, delivering a broad range of optically pure 1,5-dicarbonyl compounds with two vicinal tertiary carbon stereocenters in up to >99% ee under mild conditions. Meanwhile, stereodivergent synthesis is disclosed to yield all four stereoisomers of products. Control experiments suggest an isomerization process involved in the reaction and give an insight into the role of NEt. In addition, Mannich reaction and sulfur-Michael addition of β,γ-unsaturated 2-acyl imidazoles proceed smoothly as well under the same catalytic system.
研究β，γ-不饱和羰基化合物的多样反应性在不对称催化合成中具有重要价值。以β，γ-不饱和羰基化合物作为亲核试剂，众多对映选择性转化反应已得到充分发展，然而，在同一催化体系下，将它们不仅用作亲核试剂还用作亲电试剂的例子却很少。在此，我们报道了在手性N，N'-二氧化物金属配合物存在下，β，γ-不饱和2-酰基咪唑的区域选择性催化不对称串联异构化/α-迈克尔加成反应，在温和条件下可提供多种光学纯的1,5-二羰基化合物，其具有两个相邻的叔碳立体中心，对映体过量率高达>99%。同时，还揭示了立体发散合成可产生产物的所有四种立体异构体。对照实验表明反应中涉及异构化过程，并深入了解了三乙胺的作用。此外，在相同催化体系下，β，γ-不饱和2-酰基咪唑的曼尼希反应和硫-迈克尔加成反应也能顺利进行。
