A copper(II)-catalyzed aza-Friedel-Crafts reaction of N-(2-pyridyl)sulfonyl aldimines:: Synthesis of unsymmetrical diaryl amines and triaryl methanes
A copper(II)-catalyzed aza-Friedel-Crafts reaction of N-(2-pyridyl)sulfonyl aldimines:: Synthesis of unsymmetrical diaryl amines and triaryl methanes
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DOI：
10.1002/anie.200503305
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发表时间：
2006-01-01
影响因子：
16.6
通讯作者：
Carretero, JC
中科院分区：
文献类型：
--
作者：
Esquivias, J;Arrayás, RG;Carretero, JC
刘易斯酸催化的富电子芳族化合物与醛、酮和亚胺的加成反应（其中后者被称为氮杂-弗里德尔-克拉夫茨反应（AFCR））是一种在合成上优异的C2C键形成过程，其以完全原子经济的方式导致官能化醇和胺。[1]然而，尽管其意义重大，但这种转化仍然存在许多与官能团耐受性相关的未解决问题，无论是关于芳烃亲核试剂还是亲电子底物。例如，羰基化合物和亚胺的单Friedel-Crafts反应似乎仅限于高度亲电的底物[2]，如乙醛酸酯，[3]三氯乙醛，[4]三氟甲基亚胺，[5]或α-亚氨基酯。[3c相比之下，芳香醛[8]和它们的亚胺[3c，9]通常根据双重Friedel-Crafts反应产生对称的三芳基甲烷，这是由于中间体苄醇（或胺衍生物）在酸性反应条件下的固有不稳定性（方案1a）。三芳基甲烷显示出各种有趣的性质，并作为无色染料，[10]光致变色剂，[11]用于生成树枝状聚合物的合适构建块，[12]以及作为理论[13]和生物学[14]研究的底物受到了极大的关注。虽然有许多方法被报道用于制备对称的三芳基甲烷[15]，但不对称衍生物的合成却少得多。[16作为正在进行的关于适当官能化的N-磺酰亚胺的金属控制反应的研究计划的一部分，[18]我们在这里描述了一种宽范围的AFCR方案，该方案允许通过与两种不同的富电子芳香族化合物的顺序反应来选择性地制备结构多样的不对称二芳基胺和三芳基甲烷。（方案1b）首先，为了研究AFCR中磺酰基取代的影响，制备了一组磺酰基亚胺，1a-e，具有不同电子和配位性质的化合物容易以良好的化学产率（87-94%）制备通过苯甲醛与相应的磺酰胺的直接缩合（方案2）。[19]我们选择富电子的N-甲基吲哚[20]作为化合物1的AFCR的模型芳族亲核试剂，Cu（OTf）或Cu（OTf）2作为催化刘易斯酸[21]（10 mol%）。
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 α-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 (Scheme1a). 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 1b).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%).