Synthesis of 3-[(1-Aryl)aminomethyl]indoles

Wynne, James H.; Stalick, Wayne M.

doi:10.1021/jo020049i

Cited by 47 publications

(19 citation statements)

References 15 publications

(27 reference statements)

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“…. The synthesis of alkylindoles is mainly by Friedel Crafts alkylation,20–22 although other approaches have also been reported 23–25. Ionic bases such as hydroxides, hydrides and alkan‐1‐ides react at N ‐1 position26 whereas the covalent metallic complexes react at C‐3 27–33.…”

Section: Introductionmentioning

confidence: 99%

An efficient one‐pot synthesis of 2‐benzylpyrroles and 3‐benzylindoles

Sharma

Chouhan

Sood

et al. 2011

Applied Organom Chemis

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Section: Introductionmentioning

confidence: 99%

An efficient one‐pot synthesis of 2‐benzylpyrroles and 3‐benzylindoles

Sharma

Chouhan

Sood

et al. 2011

Applied Organom Chemis

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“…We chose the electron‐rich N ‐methylindole20 as model aromatic nucleophile for the AFCR of compounds 1 , and Cu(OTf) or Cu(OTf) 2 as catalytic Lewis acids21 (10 mol %). The effect of adding phosphane ligands to the reaction media was also examined [(±)‐binap, dppf, dppe, and PPh 3 ], with binap being the most efficient 22.…”

Section: Methodsmentioning

confidence: 99%

A Copper(II)‐Catalyzed Aza‐Friedel–Crafts Reaction of N‐(2‐Pyridyl)sulfonyl Aldimines: Synthesis of Unsymmetrical Diaryl Amines and Triaryl Methanes

2006

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The Lewis acid-catalyzed addition of electron-rich aromatic compounds to aldehydes, ketones and imines, the latter of which is known as the aza-Friedel-Crafts reaction (AFCR), is a synthetically outstanding CÀC bond-forming process that leads to functionalized alcohols and amines in a completely atom-economical way.[1] However, despite its significance, a number of unsolved aspects related to functional-group tolerance, either with regard to the arene nucleophile or the electrophilic substrate, still remain for this transformation. For instance, the mono Friedel-Crafts reaction of carbonyl compounds and imines seems to be restricted to highly electrophilic substrates [2] such as glyoxylates, [3] chloral (trichloroacetaldehyde), [4] pyruvates, [5] trifluoromethyl imines, [6] or a-imino esters. [3c, 7] In contrast, aromatic aldehydes [8] and their imines, [3c, 9] generally evolve according to a double Friedel-Crafts reaction to give symmetrical triaryl methanes due to the intrinsic instability of the intermediate benzylic alcohol (or amine derivative) under the acidic reaction conditions (Scheme 1 a). Triaryl methanes display varied and interesting properties and have received a great deal of attention as leuco dyes, [10] photochromic agents, [11] suitable building blocks for generating dendrimers, [12] and as substrates for theoretical [13] and biological [14] studies. While many methods have been reported for the preparation of symmetrical triaryl methanes, [15] the synthesis of unsymmetrical derivatives is much less developed. [16,17] As part of an ongoing research program on metalcontrolled reactions of appropriately functionalized N-sulfonyl imines, [18] we describe here a broad-scope AFCR protocol that allows the selective preparation of structurally diverse unsymmetrical diaryl amines and triaryl methanes by sequential reaction with two different electron-rich aromatic compounds (Scheme 1 b).First, to study the effect of the sulfonyl substitution in AFCR, a set of sulfonyl imines, 1 a-e, of varied electronic and coordination nature were readily prepared in good chemical yields (87-94 %) by direct condensation of benzaldehyde with the corresponding sulfonamide (Scheme 2). [19] We chose the electron-rich N-methylindole [20] as model aromatic nucleophile for the AFCR of compounds 1, and Cu(OTf) or Cu(OTf) 2 as catalytic Lewis acids [21] (10 mol %). Scheme 2. Synthesis of N-sulfonyl imines 1 a-e. M.S. = molecular sieves.

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“…3-Substituted indole moieties are important as they are widely distributed in nature and reveal a broad range of biological activities [10]. Indoles with amino alkyl/aryl substituents at the 3-position are considered as potential pharmacophores [11] in drug discovery and are found in various natural products [12], useful in the treatment of migraine, breast cancer [13], and HIV-1 [14]. The immense potential of indole nucleus for development of drug candidates, prompted many synthetic chemists to explore different methodologies suitable for the synthesis of 3-substituted indoles.…”

Section: Introductionmentioning

confidence: 99%