Well-Defined NNS-Mn Complex Catalyzed Selective Synthesis of C-3 Alkylated Indoles and Bisindolylmethanes Using Alcohols

Abstract

Herein, we demonstrated Mn-catalyzed selective C-3 functionalization of indoles with alcohols. The developed catalyst can also furnish bis(indolyl)methanes from the same set of substrates under slightly modified reaction conditions. Mechanistic studies reveal that the C-3 functionalization of indoles is going via a borrowing hydrogen pathway. To highlight the practical utility, a diverse range of substrates including nine structurally important drug molecules are synthesized. Furthermore, we also introduced a one-pot cascade strategy for synthesizing C-3 functionalized indoles directly from 2-aminophenyl ethanol and alcohol.

Synthesis of Bis(3‐indolyl)methanes Mediated by Potassium tert‐Butoxide

“…Increasing the amount of base to 1 equiv. improved the yield to 77 %; above these values, the yield decreased (entries [6][7][8]. This shows that the amount of base is crucial for product formation, as higher conversion was obtained with an equimolar amount of base.…”

“…Preparation of these compounds is usually done by addition of aldehydes or ketones to two molecules of indole via acid[ 5 , 6 ] or base catalysis. [7] Furthermore, alternative and more sustainable methods have emerged, based on metal‐catalysed[ 8 , 9 ] and metal‐free reactions. [10] This includes metal‐catalysed carbonylation and alkylation reactions[ 11 , 12 , 13 ] and organocatalysed reactions.…”

Alcohol Dehydrogenation-Triggered Selective C3-Alkylation of Indoles by Homogeneous Azo-aromatic Cobalt Catalysts

“…. 83 Yellow oil, 203 mg (77% Yield). 1 H NMR (500 MHz, chloroform-D): δ 7.85 (s, 1H), 7.61 (d, J = 7.6 Hz, 1H), 7.37−7.35 (m, 3H), 7.28−7.22 (m, 3H), 7.16−7.13 (m, 1H), 6.92 (s, 1H), 3.97 (s, 2H), 1.20 (s, 9H).…”

Single and double deprotonation/dearomatization of the N,S-donor pyridinophane ligand in ruthenium complexes

“…Replacement of phosphines with other types of “soft” donors such as sulfides may provide potentially more air-stable and cheaper ligand types with similar reactivity patterns. 12–19…”

“…Replacement of phosphines with other types of "soft" donors such as sulfides may provide potentially more airstable and cheaper ligand types with similar reactivity patterns. [12][13][14][15][16][17][18][19] At the same time, the development of N,S-donor ligands in catalysis has led to systems being developed that display good catalytic activity in hydrogenation, [20][21][22][23][24] transfer hydrogenation 25 and acceptorless dehydrogenation reactions, 26,27 sometimes exceeding the performance of phosphine-based donors.…”