A silver‐catalyzed intermolecular aminosulfonylation of terminal alkynes with sodium sulfinates and TMSN3 is reported. This three‐component reaction proceeds through sequential hydroazidation of the terminal alkyne and addition of a sulfonyl radical to the resultant vinyl azide. The method enables the stereoselective synthesis of a wide range of β‐sulfonyl enamines without electron‐withdrawing groups on the nitrogen atom. These enamines are found to be suitable for a variety of further transformations.
The hydroazidation of alkynes is the most straightforward way to access vinyl azidesversatile building blocks in organic synthesis. We previously realized such a fundamental reaction of terminal alkynes using Ag2CO3 as a catalyst. However, the high catalyst loading seriously limits its practicality, and moreover, the exact reaction mechanism remains unclear. Here, on the basis of X-ray diffraction studies on the conversion of silver salts, we report the identification of AgN3 as the real catalytic species in this reaction and developed a AgN3-catalyzed hydroazidation of terminal alkynes. AgN3 proved to be a highly robust catalyst, as the loading of AgN3 could be as low as 5 mol %, and such a small proportion of AgN3 is still highly efficient even at a 50 mmol reaction scale. Further, the combination of experimental investigations and theoretical calculations disclosed that the concerted addition mechanism via a six-membered transition state is more favored than the classical silver acetylide mechanism.
As ilver-catalyzed intermolecular aminosulfonylation of terminal alkynes with sodium sulfinates and TMSN 3 is reported. This three-component reaction proceeds through sequential hydroazidation of the terminal alkyne and addition of as ulfonyl radical to the resultant vinyl azide.T he method enables the stereoselective synthesis of aw ide range of bsulfonyl enamines without electron-withdrawing groups on the nitrogen atom. These enamines are found to be suitable for av ariety of further transformations.Alkynes are one of the most common and versatile functional groups in organic synthesis,and catalytic methods that enable their efficient transformation into other useful functionalities are therefore highly appealing in both academic research and industrial applications.[1] Direct difunctionalization reactions of alkynes,c apable of affording tri-and tetrasubstituted alkenes,h ave attracted much attention in recent years.[2] Among these,r adical-based 1,2-difunctionalizations of alkynes offer astraightforward means to construct functionalized alkenes by reaction with both carbon- [3] and heteroatom-centered radicals [4] with excellent step-and atomeconomy.[5] Mechanistically,ac ommon reaction pathway is observed involving initiation of the reaction by radical addition to the alkyne to generate av inyl radical intermediate,w hich is then coupled with another component to form the alkene product ( Figure 1a). However,s uch vinyl radical species are highly reactive and readily undergo hydrofunctionalization by H-atom abstraction, [6] which is as ignificant challenge in developing radical-based alkyne difunctionalization reactions.M oreover,a liphatic alkynes are generally unreactive in these processes,which is most likely due to the lack of a p-conjugation stabilizing effects of intermediate alkyl-substituted vinyl radicals compared to aryl-substituted analogues.[7] Consequently,c onceptually distinct approaches are in high demand. In the last years,t he nitrogenation of alkynes with trimethylsilylazide (TMSN 3 )has attracted much attention, where carbon-carbon triple bond cleavage leads to av ariety of nitrogen-containing molecules.[8] Building from our recent efforts on the activation of alkynes by silver catalysis, [9] we herein report an ew strategy to effect radicalbased difunctionalization of terminal alkynes through an unprecedented hydroazidation/ radical addition cascade (Figure 1b). Thek ey point for this successful transformation is that we discovered amild and efficient approach to generate sulfonyl radical from sodium sulfinate,t hus avoiding the initial competitive radical addition to alkynes.[6] To the best of our knowledge,t his is the first example of intermolecular alkyne aminosulfonylation, [10] resulting in stereoselective synthesis of b-sulfonyl N-unprotected enamines,w hich are useful synthetic intermediates whose applications are currently limited by al ack of practical synthetic methods for their preparation.[11] Moreover,only one report regarding the synthesis of N-unprotected enami...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.