Zhang Mao-Mao, Wang Ya-Ni, Wang Bao-Cheng, Chen Xiao-Wang, Lu Liang-Qiu, Xiao Wen-Jing
CCNU-uOttawa Joint Research Centre, Key Laboratory of Pesticide and Chemical Biology, Ministry of Education; College of Chemistry, Central China Normal University, 152 Luoyu Road, Wuhan, 430079, China.
State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics (LICP), Chinese Academy of Sciences, Lanzhou, 730000, China.
Nat Commun. 2019 Jun 20;10(1):2716. doi: 10.1038/s41467-019-10674-3.
Catalytic asymmetric cycloadditions via transition-metal-containing dipolar intermediates are a powerful tool for synthesizing chiral heterocycles. However, within the field of palladium catalysis, compared with the well-developed normal electron-demand cycloadditions with electrophilic dipolarophiles, a general strategy for inverse electron-demand ones with nucleophilic dipolarophiles remains elusive, due to the inherent linear selectivity in the key palladium-catalyzed intermolecular allylations. Herein, based on the switched regioselectivity of iridium-catalyzed allylations, we achieved two asymmetric [4+2] cycloadditions of vinyl aminoalcohols with aldehydes and β,γ-unsaturated ketones through synergetic iridium and amine catalysis. The activation of vinyl aminoalcohols by iridium catalysts and carbonyls by amine catalysts provide a foundation for the subsequent asymmetric [4+2] cycloadditions of the resulting iridium-containing 1,4-dipoles and (di)enamine dipolarophiles. The former provides a straightforward route to a diverse set of enantio-enriched hydroquinolines bearing chiral quaternary stereocenters, and the later represent an enantio- and diastereodivergent synthesis of chiral hydroquinolines.
通过含过渡金属的偶极中间体进行的催化不对称环加成反应是合成手性杂环的有力工具。然而，在钯催化领域，与已成熟的亲电偶极体参与的正常电子需求环加成反应相比，由于关键的钯催化分子间烯丙基化反应中固有的线性选择性，亲核偶极体参与的逆电子需求环加成反应的通用策略仍然难以捉摸。在此，基于铱催化烯丙基化反应区域选择性的转变，我们通过铱和胺协同催化实现了乙烯基氨基醇与醛和β,γ-不饱和酮的两种不对称[4+2]环加成反应。铱催化剂对乙烯基氨基醇的活化以及胺催化剂对羰基的活化，为后续生成的含铱1,4-偶极体与（二）烯胺偶极体的不对称[4+2]环加成反应奠定了基础。前者为合成一系列带有手性季碳立体中心的对映体富集的氢喹啉提供了直接途径，后者则代表了手性氢喹啉的对映体和非对映体发散合成。
