Catalytic asymmetric dearomative azo-Diels–Alder reaction of 2-vinlyindoles

Due to the high electrophilic nature of azo-dienophiles, azo-Diels–Alder proceeds rapidly even without the need of a catalyst and is therefore regarded as the “click reaction”. This spontaneity causes strong background reaction and poses a daunting challenge to chemists for developing the catalytic asymmetric version. Reported herein is the first catalytic asymmetric dearomative azo-Diels–Alder reaction between 2-vinylindoles and triazoledione. This protocol makes use of the high energy barrier of dearomatization to avert the strong background reaction of azo-Diels–Alder reaction, allowing the implementation of the projected reaction at ambient temperature. Density functional theory calculations have been performed to gain insights into the reaction mechanism and the origins of the enantioselectivity. By using this method, a variety of tetracyclic indole derivatives have been readily prepared in good to excellent yields and with excellent diastereo- and enantio-selectivities (33 examples, up to 97% yield and > 99% ee, > 20:1 dr).