Introduction

The Truce-Smiles rearrangement is an efficient strategy to form C−C bonds under metal-free conditions.^{1, 2} In this process, an electrophilic sp2 carbon undergoes intramolecular attack by a carbanion that originates from an activated C−H bond. The rearrangement proceeds via a 4–6 membered spiro-Meisenheimer complex, which is spontaneously converted to a C-arylated product. Recently, the Truce-Smiles rearrangement of natural amino acid-based 2/4-nitrobenzenesulfonamides was widely investigated as a route to different nitrogen heterocycles via Cα-arylation, in which C−H was typically activated by the adjacent carbonyl group (Scheme 1).^3-8 Inspired by this approach, we suggested the use of 2/4-nitrobenzenesulfonamides originating from 2-aminobenzyl cyanide alkylated by scaffolds without electron-withdrawing groups. Consequently, instead of undergoing Cα-arylation, these substrates may be amenable to Cγ-arylation, which would eventually yield 2-aminoindoles.

Indoles are highly relevant compounds in pharmacological fields and exhibit a broad range of biological effects.⁹ Although many synthetic routes leading to substituted and functionalized indoles have been reported, synthetic strategies for accessing 2-aminoindoles are rather limited. One of the oldest methods is based on the Curtius rearrangement of indolyl-2-carboxylic acid azide.¹⁰ Later, amination of the corresponding 2-nitro⁸ or 2-acyl^{12, 13} indoles to prepare 1-substituted 2-amino-3-arylindoles was reported. In alternative synthetic routes, alkynylamines have been used as the starting material for reactions with aniline-based sulfilimines¹⁴ or alkylazides.¹⁵ C−H amination of N-acyl-3-arylindo moieties via an electrooxidative cross-coupling process was developed by Feng et al.¹⁶ and the condensation of 2-(2-nitrophenyl)acetonitrile leading to N-hydroxy-2-amino-3-arylindoles was reported by Belley et al.¹⁷

To date, the most frequently studied strategies consist of rhodium-catalyzed,¹⁸ Pd-catalyzed,¹⁹ triflic acid-catalyzed¹⁷ or BF₃- promoted²¹ arylation of 3-diazoindoline-2-imines. In this article, we report the development of a metal-free approach starting from commercially available reagents and building blocks.

中文翻译：

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通过分子内 C-芳基化合成 2-氨基-3-芳基吲哚及其稠合类似物

介绍

Truce-Smiles 重排是在无金属条件下形成 C−C 键的有效策略。^{1, 2}在此过程中，亲电sp 2 碳会受到源自活化 C−H 键的碳负离子的分子内攻击。重排通过4-6 元螺-迈森海默复合物进行，该复合物自发转化为 C-芳基化产物。最近，基于天然氨基酸的 2/4-硝基苯磺酰胺的 Truce-Smiles 重排被广泛研究，作为通过Cα-芳基化生成不同氮杂环的途径，其中 C−H 通常被相邻的羰基激活（方案 1） 。^3-8受此方法的启发，我们建议使用源自 2-氨基苄氰的 2/4-硝基苯磺酰胺，并通过不含吸电子基团的支架进行烷基化。因此，这些底物可能不进行 Cα-芳基化，而是进行 Cγ-芳基化，最终产生 2-氨基吲哚。

吲哚是药理学领域高度相关的化合物，并表现出广泛的生物效应。⁹尽管已报道了许多产生取代和官能化吲哚的合成路线，但获得 2-氨基吲哚的合成策略相当有限。最古老的方法之一是基于吲哚基-2-甲酸叠氮化物的库尔蒂斯重排。¹⁰随后，报道了将相应的 2-硝基⁸或 2-酰基^{12, 13}吲哚胺化以制备 1-取代的 2-氨基-3-芳基吲哚。在替代合成路线中，炔胺已被用作与苯胺基硫亚胺¹⁴或烷基叠氮化物反应的起始材料。 Feng等人开发了通过电氧化交叉偶联过程对N-酰基-3-芳基林基部分进行¹⁵ C−H胺化的方法。 Belley 等人报道了¹⁶和 2-(2-硝基苯基)乙腈缩合生成N-羟基-2-氨基-3-芳基吲哚。^{17 号}

迄今为止，最常研究的策略包括铑催化、¹⁸ Pd 催化、¹⁹三氟甲磺酸催化¹⁷或 BF ₃ - 促进3-重氮吲哚啉-2-亚胺的²¹芳基化。在本文中，我们报告了从市售试剂和构建模块开始的无金属方法的开发。