Alkyne Versus Ynamide Reactivity: Regioselective Radical Cyclization of Yne‐Ynamides

Abstract

Ynamides are typically more reactive than simple alkynes and olefins. However, a serendipitous observation revealed a rare case where the reactivity of simple alkynes exceeds that of ynamides. This led to the development of a unique sulfur‐radical‐triggered cyclization of yne‐tethered ynamides, which involves attack of the alkyne by a thiyl radical followed by cyclization with the ynamide. A wide range of novel 4‐thioaryl pyrroles that could tolerate common functional moieties and N‐protecting groups were expediently constructed by this strategy. The current method contrasts with the typical cyclization of yne‐ynamides, which involves the attack of the alkyne moiety by the ynamide core. Control experiments and DFT calculations supported the participation of the sulfur radical in the reaction and the regioselective cyclization. The synthetic potential of the substituted pyrroles is also discussed.

A Radical-Initiated Fragmentary Rearrangement Cascade of Ene-Ynamides to [1,2]-Annulated Indoles via Site-Selective Cyclization

“…First, the radical precursor undergoes single electron transfer with copper(I) complex (or the photoexcited *Ir III catalyst) to generate a copper(II) species (or Ir IV species) and radical •X (•CF 2 R) which then undergoes intermolecular addition to the alkene part in the ynamide 1 furnishing alkyl radical intermediate I. 17 Intramolecular cyclization to generate vinyl radical intermediate II precedes ipso-cyclization onto the sulfonamide and desulfonylation to generate the N-centered radical intermediate III. Oxidation of III by copper(II) complex (or Ir IV species) would generate the extended cation IV and regenerate the copper(I) catalyst (or Ir III catalyst).…”

Thiyl Radicals: Versatile Reactive Intermediates for Cyclization of Unsaturated Substrates

“…The use of thiyl radical addition/cyclization has been previously described as a useful route to thiophenes, through clever use of homolytic substitution reactions. Possibly the most recent cyclization of a diyne substrate was reported by Dutta et al, in which a number of pyrroles were prepared ( Scheme 16 ) [ 64 ]. This account describes the use of ynamides and alkynes for cyclization; the authors report a ‘serendipitous observation’ that the reactivity of simple alkynes was found to exceed the traditionally more reactive ynamides moieties for cyclization.…”

Keteniminium Induced Dienone‐Phenol Rearrangement and Intramolecular 6‐endo‐dig Cyclization Cascade of Yne‐Dienone

“…Based on the previous findings and our ongoing research on ynamide [26][27][28][29][30] and yne-dienone, [31 -33] we envisioned a gold-catalyzed keteniminium driven dienone-phenol rearrangement of yne-dienone IV, which to the best of our knowledge is rare (Scheme 1,c). The transformation possibly involves dienone-phenol rearrangement with 1,2-migration of 4-substituted ynedienone and a regioselective intramolecular 6-endodig cyclization of in-situ formed aryl-propargyl ether VII cascade (Scheme 1,c).…”