Catalytic Asymmetric Inverse-Electron-Demand Oxa-Diels-Alder Reaction of In Situ Generated ortho-Quinone Methides with 3-Methyl-2-Vinylindoles

• Published in: Angewandte Chemie Vol. 127; no. 18; pp. 5550 - 5554
• Main Authors: Zhao, Jia-Jia, Sun, Si-Bing, He, Sai-Huan, Wu, Qiong, Shi, Feng
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 27.04.2015; WILEY‐VCH Verlag
• Subjects: Asymmetrische Katalyse; Cycloadditionen; Enantioselektivität; Heterocyclen; Organokatalyse
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201500215

The first catalytic asymmetric inverse‐electron‐demand (IED) oxa‐Diels–Alder reaction of ortho‐quinone methides, generated in situ from ortho‐hydroxybenzyl alcohols, has been established. By selecting 3‐methyl‐2‐vinylindoles as a class of competent dienophiles, this approach provides an efficient strategy to construct an enantioenriched chroman framework with three adjacent stereogenic centers in high yields and excellent stereoselectivities (up to 99 % yield, >95:5 d.r., 99.5:0.5 e.r.). The utilization of ortho‐hydroxybenzyl alcohols as precursors of dienes and 3‐methyl‐2‐vinylindoles as dienophiles, as well as the hydrogen‐bonding activation mode of the substrates met the challenges of a catalytic asymmetric IED oxa‐Diels–Alder reaction. Drei in einer Reihe: In der Titelreaktion werden ortho‐Chinonmethide in situ aus ortho‐Hydroxybenzylalkoholen erzeugt und mit 3‐Methyl‐2‐vinylindolen als Dienophile umgesetzt. Dieser Ansatz führt in hohen Ausbeuten zu enantiomerenangereicherten Chromangerüsten mit drei benachbarten Stereozentren. CPA=chirales Phosphorsäurederivat.