Laboratory of Synthesis and Natural Products, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, EPFL-SB-ISIC-LSPN, BCH 5304, 1015, Lausanne, Switzerland.
Angew Chem Int Ed Engl. 2018 Feb 12;57(7):1995-1999. doi: 10.1002/anie.201712521. Epub 2018 Jan 16.
Reported is an unprecedented catalytic enantioselective desymmetrizing aza-Wacker reaction. In the presence of a catalytic amount of a newly developed Pd(CPA) (MeCN) catalyst (CPA=chiral phosphoric acid), a pyrox ligand, and molecular oxygen, cyclization of properly functionalized prochiral 3,3-disubstituted cyclohexa-1,4-dienes afforded enantioenriched cis-3a-substituted tetrahydroindoles in good yields with excellent enantioselectivities. A cooperative effect between the phosphoric acid and the pyrox ligand ensured efficient transformation. This reaction was tailor-made for Amaryllidaceae and Sceletium alkaloids as illustrated by its application in the development of the concise and divergent total synthesis of (-)-mesembrane and (+)-crinane.
报告了首例非对映选择性的钯催化氮杂 Wacker 反应。在新型 Pd(CPA)(MeCN)催化剂（CPA=手性磷酸）、Pyrox 配体和分子氧存在下，对合适官能化的前手性 3,3-二取代环己-1,4-二烯进行环化反应，以高产率和优异的对映选择性得到了富集顺式-3a 取代的四氢吲哚。磷酸和 Pyrox 配体之间的协同作用确保了高效转化。该反应特别适用于石蒜科和石蒜属生物碱，如在简洁和发散的 (-)-mesembrine 和 (+)-crinane 的全合成中的应用所示。
