Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu, 610064, China.
Collaborative Innovation Center of Chemical Science and Engineering, Tianjin, 300071, China.
Nat Commun. 2018 May 17;9(1):1968. doi: 10.1038/s41467-018-04123-w.
Although great success has been achieved in asymmetric Claisen rearrangement for the synthesis of chiral γ,δ-unsaturated carbonyl compounds bearing vicinal tertiary-quaternary stereocenters, the development of asymmetric versions for stereodivergent construction of adjacent quaternary-quaternary stereocenters remains a formidable challenge because of the high steric hindrance. Here we report a catalytic enantioselective dearomatization Claisen rearrangement of allyl furyl ethers catalyzed by chiral N,N'-dioxide-Ni complex catalysts. A variety of chiral γ,δ-unsaturated carbonyl compounds bearing vicinal quaternary-quaternary stereocenters were obtained with excellent outcomes under mild conditions. Furthermore, we disclosed that by matching the configuration of the catalysts and the alkene unit of the substrates, four stereoisomers of the products could be prepared in excellent yields and stereoselectivities. Finally, the fascination of this strategy was demonstrated by stereodivergent synthesis of bioactive natural products hyperolactones B, C, and their epimers. A possible catalytic model was proposed to explain the origin of the asymmetric induction.
尽管在手性γ，δ-不饱和羰基化合物的合成中，不对称 Claisen 重排已取得巨大成功，这些化合物具有相邻的叔-季立体中心，但由于空间位阻大，发展立体发散构建相邻的季-季立体中心的不对称版本仍然是一个巨大的挑战。在此，我们报道了手性 N，N'-二氧化氮-镍配合物催化剂催化的烯丙基呋喃醚的催化对映选择性去芳构化 Claisen 重排反应。在温和条件下，通过该方法可以获得多种具有相邻季-季立体中心的手性γ，δ-不饱和羰基化合物，产率和立体选择性都很高。此外，我们发现通过匹配催化剂和底物的烯烃单元的构型，可以以优异的产率和立体选择性制备产物的四个立体异构体。最后，通过立体发散合成生物活性天然产物 hyperolactones B、C 及其表异构体，证明了该策略的魅力。提出了一个可能的催化模型来解释不对称诱导的起源。
