Organocatalytic Michael Addition of Indoles to α‐Substituted Enals by Using a Diazepane Carboxylate Catalyst

Abstract

The conjugate addition of indoles to α‐substituted enals is achieved by using a diazepane carboxylate catalyst under mild conditions (20 mol‐% catalyst, 20 mol‐% TFA, acetonitrile, –20 °C). The low basicity and high nucleophilicity of this catalyst overcomes the limitations of allylic 1,3 strain in the intermediate iminium ions, which is normally observed with secondary‐amine catalysts. Conjugate addition of a series of substituted indoles as well as electron‐rich aromatics with a variety of α‐substituted enals is demonstrated.

Mechanism of an Organocatalytic Cope Rearrangement Involving Iminium Intermediates: Elucidating the Role of Catalyst Ring Size

“…Hydrazide catalysts have previously been examined as organocatalysts in the Diels−Alder reaction, and differences between fiveand six-membered ring catalysts have been previously observed. 33 We have found that the sevenmembered ring hydrazide is particularly effective in a range of reactions of α-substituted-α,β-unsaturated aldehydes, including Michael additions, 34 Diels−Alder cycloadditions, 35 and even polyene cyclizations. 36 Importantly, the formation of iminium ions with these substrates is normally quite difficult due to the development of significant A-1,3 interactions.…”

First Report on 3‐(3‐oxoaryl) Indole Derivatives as Anticancer Agents: Microwave Assisted Synthesis, In Vitro Screening and Molecular Docking Studies

“…In particular, the synthesis of 3‐(3‐oxoaryl) indole derivatives attracted much attention and have been reported by several groups via Michael addition of indole derivatives with various α,β ‐unsaturated ketones in the presence of several Lewis acid based catalysts such as HfCl 4 and ScCl 3 , CAN, InBr 3 , Bi(NO 3 ) 3 , GaCl 3 , Cu(OTf) 2 , I 2 , AlCl 3 , BF 3 .OEt 2 etc . In addition to that, a few reports are available for the Michael addition of indole with chalcone using other catalyst and organocatalysts …”

“…[18][19][20][21][22][23][24][25][26][27] In addition to that, a few reports are available for the Michael addition of indole with chalcone using other catalyst [28][29] and organocatalysts. [30] However, the reported methods have one or several drawbacks such as use of moisture sensitive catalyst, toxic organic solvent, expensive reagents, long reaction time, low catalytic activity, low reaction yields etc. Thus, it was desirable to develop an efficient method for the synthesis of 3-(3-oxoaryl) indole derivatives through green chemistry approach.…”

Diazepane Carboxylates as Organocatalysts in the Diels–Alder Reaction of α‐Substituted Enals

“…In the course of developing an organocatalytic Cope rearrangement, we identified ethyl diazepane carboxylate 1a as a highly effective catalyst with the unusual ability to form iminium ions from α‐substituted enals, including substrates bearing quaternary centers at the alpha position (Scheme ) . We subsequently found that 1a was also effective in catalyzing the Michael addition of indoles and other electron rich aromatics to α‐substituted enals . Both cyclic and acyclic hydrazides have been previously developed as catalysts for the Diels–Alder reaction of simple α‐unsubstituted enals .…”