A Robust One-Step Approach to Ynamides

Abstract

A robust one-step synthetic strategy for ynamide with cheap and easily available stock chemicals vinyl dichlorides and electron deficient amides as the starting material is described. In the absence of transition-metal catalyst, the reaction proceeds under mild reaction conditions in open air and thus rendering a convenient operation. This strategy is not only suitable for both terminal and internal ynamide synthesis but also amenable for large-scale preparation. Broad substrate scopes with respect to vinyl dichloride as well as electron-deficient amide were observed.

Metal‐Free Cyclization ofortho‐Nitroaryl Ynamides and Ynamines towards Spiropseudoindoxyls

“…The initial loss of HBr from dibromoalkene 1 a affords bromoalkyne 5 , which can undergo an addition/elimination sequence towards ynamide 3 a . To the best of our knowledge, only few references make note of the transformation of a dihaloalkane into an ynamide without a transition‐metal catalyst . This ynamide could then undergo two distinctive pathways, namely a) attack of an oxygen atom of the nitro group at the β‐position of the ynamide, which would eventually generate the stabilized carbene 8 , or b) attack of the ynamide at an oxygen atom of the nitro group, which also leads to carbene 8 .…”

Divergent Reactions between Alkynes and Dibenzenesulfonimide: Selective Synthesis of Ynamides and Enamides under Metal‐Free Conditions

“…However most of these methods are limited to internal alkynes or their derivetives and usually suffered from the side reaction copper‐catalyzed alkyne homo‐coupling. Efficient strategy for access of ynamides from simple alkynes preferably under metal‐free conditions is still highly desired . Stang and coworkers first prepared ynamides through direct coupling of alkynyl iodonium (III) salts with lithium amides (Scheme b) .…”

A Micellar Catalysis Strategy for Amidation of Alkynyl Bromides: Synthesis of Ynamides in Water

“…Ynamides, displaying an optimal balance of stability and reactivity, have become a privileged building blocks for the synthesis of highly versatile nitrogen‐containing molecules including bioactive agents and natural products, Accordingly, many synthetic strategies for ynamides have been developed since the first synthesis by Viehe in 1972 . Among all of these known methods, arguably one of the best routes to ynamides was the copper‐catalyzed amidation of alkynyl bromides by Hsung . However, this strategy, as well as others, tends to require dry organic solvents (e.g., toluene, DMF, DMSO, DCM) and relatively high temperatures.…”