Introduction

Carbenes, highly useful neutral divalent reaction intermediates, rarely exist as free stable species and they usually need to be prepared from appropriate precursors, of which metal carbene complexes and N-sulfonyl hydrazones are two prime sources (Scheme 1a). Interestingly, both types of compounds have found paramount application in synthetic organic chemistry. Particularly, group 6 metal Fischer carbene complexes (FCCs) have shown to be highly valuable reagents,¹ not only as carbene precursors but also by displaying a wide-range of reactivity patterns (chemical multitalents).² Specifically, they have found remarkable application in heterocyclic synthesis, becoming appropriate starting materials for the preparation of three- to eight-membered ring heterocycles.³ Noting the popularity of the classic Bamford-Stevens and Shapiro reactions, the great synthetic versatility of N-tosylhydrazones (NTHs) has been demonstrated in organic chemistry⁴ both as precursors of diazo compounds⁵ and in cross-coupling reactions, either catalyzed by a metal⁶ or without metal catalysis.⁷ In addition, the only example to date of a reaction involving both tosylhydrazones and Fischer carbene complexes, reported by J. Wang, describes the coupling between aromatic aldehyde derived tosylhydrazones and methoxy aryl chromium carbene complexes for the synthesis of 1,2-diarylethanones (Scheme 1b).⁸ NTHs have shown indeed a chameleonic behavior in their reactions with alkynes, operating either as synthons of three atom units ([CNN] synthons, which is the most usual manner) to form pyrazoles in [3+2] cycloaddition reactions^[9.10] or as synthons of a carbon atom ([C] synthons) in cyclopropenation reactions,¹¹ depending mainly on the nature of the tosylhydrazone (Scheme 1c). They also can act as [C] synthons with alkenes¹² and fullerenes¹³ to form cyclopropanes.

With this state of the art, we have planned to analyze the behavior of these two carbene sources under the same reaction conditions by extending the reactivity of NTHs to a very special class of alkynes: alkoxy alkynyl group 6 metal FCCs. By considering the functional groups present in the FCC individually, three main patterns were foreseen for the reaction between these two species (Scheme 1d): (i) a C−C coupling, not really expected because of the low propensity to C−C coupling of alkoxy alkynyl FCCs; (ii) a [2+1] or (iii) a [3+2] cycloaddition reactions with the NTH acting respectively as a [C]- or a [CNN]-synthon. However, the product obtained under the tested reaction conditions turned out to be an alkenyl pyrazole derived from a behavior of the NTH as a [NN] synthon. When those initial results were reached, they represented an unprecedent finding as, for the first time, only the two N atoms partake in the cycloaddition reaction.¹⁴ However, more recently, such behavior has also been observed in the copper(I)-catalyzed reaction of NTHs derived of β-ketoesters and aromatic propargyl acetates (Scheme 1e).¹⁵

Although the [NN] synthon behavior of NTHs is, indeed, a major finding reported in this current research, it is also worth mentioning that pyrazoles show a wide range of biological and pharmaceutical activities,¹⁶ so a variety of synthetic approaches to them have been developed;¹⁷ however, the number of methods to prepare N-alkenyl pyrazoles is rather limited,¹⁰ and they are mainly based in the direct addition of N-unsubstituted pyrazoles to alkynes.¹⁸ Therefore, the development of new protocols to access N-alkenyl pyrazoles involving the de novo construction of the pyrazole ring is highly valued.

中文翻译：

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N-甲苯磺酰腙作为杂环化学中的 [N,N] 合成子：3,5-二取代的 N-烯基-1H-吡唑的合成

介绍

卡宾是非常有用的中性二价反应中间体，很少以游离稳定物质形式存在，通常需要由适当的前体制备，其中金属卡宾配合物和N-磺酰腙是两个主要来源（方案1a）。有趣的是，这两种类型的化合物在合成有机化学中都有重要的应用。特别是，第 6 族金属费歇尔卡宾配合物 (FCC) 已被证明是非常有价值的试剂，¹不仅作为卡宾前体，而且还表现出广泛的反应模式（化学多才多艺）。²具体来说，它们在杂环合成中具有显着的应用，成为制备三至八元环杂环的合适原料。³注意到经典的 Bamford-Stevens 和 Shapiro 反应的流行，N-甲苯磺酰腙 (NTH) 的巨大合成多功能性已在有机化学⁴中得到证明，既可以作为重氮化合物⁵的前体，也可以在交叉偶联反应中（由金属⁶或无金属催化。⁷此外，J. Wang 报道的迄今为止涉及甲苯磺酰腙和 Fischer 卡宾络合物的唯一反应实例描述了芳香醛衍生的甲苯磺酰腙和甲氧基芳基铬卡宾络合物之间的偶联，用于合成 1,2-二芳基乙酮（方案 1b)。⁸ NTH 在与炔烃的反应中确实表现出了变色龙行为，可以作为三个原子单元的合成子（[CNN]合成子，这是最常见的方式）在 [3+2] 环加成反应中形成吡唑^[9.10]或作为环丙烯化反应中碳原子的合成子（[C]合成子）， ¹¹主要取决于甲苯磺酰腙的性质（方案 1c）。它们还可以作为[C]合成子与烯烃¹²和富勒烯¹³形成环丙烷。

凭借这一最先进的技术，我们计划通过将 NTH 的反应活性扩展到一类非常特殊的炔烃：烷氧基炔基 6 金属 FCC，来分析这两种卡宾源在相同反应条件下的行为。通过单独考虑 FCC 中存在的官能团，可以预见这两种物质之间的反应的三种主要模式（方案 1d）： (i) C−C 偶联，由于 C−C 偶联的倾向较低，因此并未真正预期到。烷氧基炔基 FCC； (ii) [2+1] 或 (iii) [3+2] 环加成反应，其中 NTH 分别充当[C]-或[CNN]-合成子。然而，在测试的反应条件下获得的产物结果是源自NTH作为[NN]合成子的行为的烯基吡唑。当获得这些初步结果时，它们代表了一个前所未有的发现，因为第一次只有两个 N 原子参与环加成反应。¹⁴然而，最近，在铜 (I) 催化的 β-酮酯和芳香族乙酸炔丙酯衍生的 NTH 反应中也观察到了这种行为（方案 1e）。¹⁵

虽然NTH 的[NN]合成子行为确实是当前研究中报告的一项重大发现，但还值得一提的是，吡唑显示出广泛的生物和药物活性，¹⁶因此，人们对其进行了多种合成方法。发达;如图¹⁷所示，然而，制备N-烯基吡唑的方法的数量相当有限，^10种，并且它们主要基于N-未取代的吡唑与炔烃的直接加成。¹⁸因此，开发涉及从头构建吡唑环的N-烯基吡唑新方案受到高度重视。