A General Copper-Catalyzed Synthesis of Ynamides from 1,2-Dichloroenamides

Abstract

Ynamides are accessed via copper-catalyzed coupling of Grignard or organozinc nucleophiles with chloroynamides, formed in situ from 1,2-dichloroenamides. The reaction exhibits broad substrate scope, is readily scaled, and overcomes typical limitations in ynamide synthesis such as the use of ureas, carbamates, and bulky or aromatic amide derivatives. This modular approach contrasts with previous routes by installing both the N-and C-substituents of the ynamide as nucleophilic components.

Recent Advances in the Synthesis of Ynamides

“…反应分两步进行: 第一步 是磺酰胺在碱性条件下与三氯乙烯反应生成 1,2-二氯烯 酰胺, 第二步是在苯基锂作用下形成炔基锂中间体后加 入各种亲电试剂形成炔酰胺. 2019 年, 该小组 [17] 还发现 1,2-二氯烯酰胺在双(三甲基硅基)氨基锂(LiHMDS)作用 下形成氯代炔酰胺中间体, 再在铜催化条件下可以与各 种金属试剂反应生成一系列炔酰胺(Scheme 7b).…”

N-Metallocenyl Ynamides: Preparation, Oxidative Functionaliza-tion and Synthesis of an ansa[3]-Ferrocenylamide

“…To overcome this issue, we used the strategy developed by Anderson, which relies on a dichloroenamide as the key intermediate. [16,28] Thus, 1,2-dichloroenamide intermediate 7 was obtained in 97% yield through the reaction of amide 6 with dichloroacetylene generated in situ by deprotonation of trichloroethylene (TCE, Scheme 2). The synthesis of ynamide 8 was then achieved through a lithium base-mediated deprotonation followed by Cl-Li exchange using an excess of PhLi.…”

“…Because of its highly interesting structural and electrochemical properties, [14] ferrocene (Fc) is a privileged moiety for such an endeavor. To the best of our knowledge, only two ferrocene-containing ynamides have been reported in the literature: acridinone derivative 1 by Robinson et al [15] and Ntosylynamide 2 by Anderson et al [16] (Figure 1). In both cases, the metallocene is connected to the triple bond and no chemical reactivity was explored, although the group of Robinson did perform some spectroelectrochemistry studies on 1.…”

Reactant-Induced Photoactivation of a Gold-Catalyzed Csp2-Csp Cross-Coupling Leading to Indoles

“…Interestingly, this substrate has been only described once by Danheiser who used it as a [2+2] cycloaddition partner. 53 From a broader perspective, very few examples of metal-catalyzed cross-coupling of such haloynamides have been published, all of them from bromo-or chloro-ynamides with copper 54,55,56 but none with gold. Gratifyingly, though 2-iodo-ynamide 7 reacted a little bit less efficiently than iodoalkynes 2 with anilines 1, a series of functionalized scaffolds 8 (for instance 8b 28) was obtained.…”