Organocatalytic Multiple Cascade Reactions: A New Strategy for the Construction of Enantioenriched Tetrahydrocarbazoles

Abstract

A novel cascade Friedel-Crafts alkylation/ Michael addition/aromatization reaction of 2-vinylindoles with a,b-unsaturated aldehydes has been developed for the construction of functionalized tetrahydrocarbazoles. The products were obtained in up to 97% yield and with excellent stereoselectivities (ee up to > 99%, dr up to > 99:1).

Iridium‐Catalyzed Asymmetric Allyl­ic Substitutions with Bulky ­Amines/Oxidative Double Bond Cleavage – Entry into the Reetz Synthesis of Amino Alcohols

“…Meanwhile, Ricci and co‐workers disclosed an asymmetric Diels–Alder reaction to afford a variety of enantiomerically pure tetrahydrocarbazoles 10b,c. In the context of our ongoing interest in the synthesis of biological important carbon‐ and heterocycles,11 we have also developed several examples of enantioselective cycloaddition reactions of 2‐vinylindoles with nitroolefins12a and enals 12b. Herein, we further advance the use of 2‐vinylindoles12c, d to develop a chiral Lewis acid complex‐catalyzed enantioselective [4+2] cycloaddition with 3‐nitro‐2 H ‐chromenes [Equation (1)].…”

2‐ and 3‐Vinylindoles as 4π Components in Cycloaddition Reactions

“…However, an alternative stepwise pathway cannot be ruled out. Indeed, in a related paper by Chen, Xiao, and co‐workers, a stepwise mechanism was proposed for the closely related [4+2] cycloaddition between 2‐vinylindoles and α,β‐unsaturated aldehydes catalyzed by a diarylprolinol silyl ether (Scheme ) …”

Strategies for the asymmetric functionalization of indoles: an update

“…Using an ''iminium'' and then an ''iminium/ enamine'' activation strategy, the authors were able to prepare tetrahydrocarbazole carbaldehydes from 2-vinylindoles and enals in 44-97% yields with 99 : 1 dr (except for 1-benzyl-2vinylindole and 2-butenal in which dr was 76 : 24) and 56-99% ee (acrolein gave the worst enantioselectivity) (Scheme 56). 134 The inherent steric interference of the catalyst was found to be able to prevent the cyclization step, thus a number of diarylprolinol silyl ethers-acid couples were tested, and 5e/HClO 4 was found to be the best one. Moreover, both (E) and (Z)-hex-2-enals gave the desired product with the same configuration, thus indicating that the cascade pathway is more favourable than the alternative D-A cycloaddition route.…”

“…133 Scheme 56 Highly substituted tetrahydrocarbazoles through iminium/ enamine cascade reactions. 134 This journal is © The Royal Society of Chemistry 2015 as aldehydes in the reaction described in this section. 147 This method allowed the enantioselective synthesis of highly functionalized cyclohepta[b]indoles in 50-72% yields with 70 : 30-89 : 11 dr and 87-96% ee (Scheme 82).…”