Preparation of Hexahydrocarbazole Derivatives by Reductive Indolization

Abstract

The reductive indolization is a two‐step protocol performed in one flask: First, the acid‐mediated Fischer indolization of a cyclic ketone with phenylhydrazine forms an iminium ion which is subsequently reduced by a hydrido borate reagent to the indoline as the final product. We utilized this new strategy for the preparation of hexahydrocarbazole derivatives with a side chain in the quaternary C4a‐position. Starting materials were several N1‐ and aryl‐substituted phenylhydrazines and a cyclic ketone with propanoic ester moiety, which is the product of the conjugated addition of cyclohexanone to ethyl acrylate. Furthermore, benzannulated congeners as well as a pyrido[4,3‐b]indole derivative were accessed. The hexahydrocarbazole defines a molecular scaffold with two points of diversification. Therefore, several derivatives at N9 and at the C4a‐side chain were prepared.

Allylation of C‐, N‐, and O‐Nucleophiles via a Mechanochemically‐Driven Tsuji–Trost Reaction Suitable for Late‐Stage Modification of Bioactive Molecules

“…Alternatively, the acceleration of the reaction by addition of water might be due to the effect of liquid assisted grinding, [25] or a combination of both factors. Interestingly, when employing terminal allyl ammonium compounds, exclusively linear products were obtained with moderate to excellent yields (44)(45)(46)(49)(50)(51).…”

“…Subsequently, we explored the versatility of substituted allyl ammonium salts (Scheme 2) with O-, N-, and Cnucleophiles (42)(43)(44)(45)(46)(47)(48)(49)(50)(51). These salts can be readily derived from the respective allyl chlorides by reacting with Me 3 N solution.…”

Allylation of C‐, N‐, and O‐Nucleophiles via a Mechanochemically‐Driven Tsuji–Trost Reaction Suitable for Late‐Stage Modification of Bioactive Molecules

“…The authors have cited additional references within the Supporting Information. [ 20 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]…”

Assembly of tetracyclic tetrahydrocarbazoles via a visible-light promoted cascade process

“…In this reaction, the tetracyclic tetrahydrocarbazole compound was isolated as a by-product in a poor yield (Scheme 1b). 8 The intramolecular Diels–Alder reaction represented another strategy, which used 2-nitroethenyl indole linked by an alkynyl chain at the N atom as the substrate. The Diels–Alder reaction was conducted at an extremely high temperature and the product was obtained in 40% yield.…”