Masson-Makdissi Jeanne, Prieto Liher, Abel-Snape Xavier, Lautens Mark
Department of Chemistry, University of Toronto, 80 St. George Street., Toronto, Ontario, M5S 3H6, Canada.
Department of Organic and Inorganic Chemistry, University of the Basque Country (UPV/EHU), P.O. Box 644, 48080, Bilbao, Spain.
Angew Chem Int Ed Engl. 2021 Jul 26;60(31):16932-16936. doi: 10.1002/anie.202105800. Epub 2021 Jun 29.
This study demonstrates the feasibility and inherent benefits of combining two distinct asymmetric transition-metal-catalyzed reactions in one pot. The reported transformation features a Pd-catalyzed asymmetric allylic alkylation and a Rh-catalyzed enantioselective 1,4-conjugate addition, effectively converting simple allyl enol carbonate precursors into enantioenriched cyclic ketones with two remote stereocenters. Despite the anticipated challenges associated with controlling stereoselectivity in such a complex system, the products are obtained in enantiomeric excesses ranging up to >99 % ee, exceeding those obtained from either of the individual asymmetric reactions. In addition, since the stereoselectivity of both steps is under catalyst control, this one-pot reaction is enantio- and diastereodivergent, enabling facile access to all stereoisomers from the same set of starting materials.
本研究证明了在一锅反应中结合两种不同的不对称过渡金属催化反应的可行性和内在优势。所报道的转化反应具有钯催化的不对称烯丙基烷基化和铑催化的对映选择性1,4-共轭加成，能有效地将简单的烯丙基烯醇碳酸酯前体转化为具有两个远程立体中心的对映体富集的环状酮。尽管在如此复杂的体系中控制立体选择性存在预期的挑战，但产物的对映体过量可达>99% ee，超过了单独任何一个不对称反应所得到的结果。此外，由于两个步骤的立体选择性均受催化剂控制，这种一锅反应是对映和非对映发散的，能够从同一组起始原料轻松获得所有立体异构体。
