Straightforward Synthesis of 3‐Aminothiophenes Using Activated Amides

Abstract

Herein, we describe a facile approach towards the synthesis of diversely substituted 3‐aminothiophenes. A wide range of functional groups can be incorporated at the C(2), C(4), and C(5) positions of the thiophenes, and this route is also suitable for the synthesis of fused bicyclic heterocycles such as 3‐aminotetrahydrobenzothiophenes. This methodology relies on a 6π‐electrocyclization involving a vinyl sulfide linked to a keteniminium salt, the latter being formed in‐situ through activation of the corresponding amide with triflic anhydride.

Synthesis of Benzazepinones via Intramolecular Cyclization Involving Ketene Iminium Intermediates

“…Among the plethora of accessible scaffolds, cyclobutanones stemming from a [2+2] cycloaddition with an alkene partner are undeniably the most often encountered and can be performed intermolecularly as well as intramolecularly . Besides that, other reactions involving keteniminium intermediates have been described more recently such as 6 π ‐electrocyclizations leading to 3‐aminobenzothiophenes, aminonaphthalenes, and more recently, 3‐aminothiophenes . The formation of 1,4‐dicarbonyl compounds mediated by sulfonium rearrangement as well as 5‐membered ring heterocycle generation or ortho ‐amino‐arylation of amides are few examples to demonstrate the great flexibility of this chemistry.…”

Keteniminium Salts as Key Intermediates for the Efficient Synthesis of 3‐Amino‐Indoles and ‐Benzofurans

“…We wanted to highlight that the cyclization step occurred indeed on the keteniminium salt, and not on the iminium intermediate resulting from the triflation of the amide. Previously, we demonstrated this by carrying out the reaction in the absence of base . Activation of the amide by triflic anhydride would give rapidly the iminium IMI2 but without the 2‐fluoropyridine in the medium, the formation of the keteniminium KET2 would occur very slowly ( Table ).…”

“…In the case of the phenyl ether, the [2+2] was still favored when n =1, giving a mixture of two regioisomers, but when n =2, no cycloadduct was observed, and the 3‐aminobenzofuran was the only isolable product. With the aniline derivative, in each case, no product arising from a [2+2] cycloaddition was observed and only formation of the desired indoles, together with an unexpected side ketoamide product, were isolated.…”

“…Based on our previous work on the direct formation of 3‐amino(benzo)thiophenes C from easily accessible thioacetamides A , through a 6 π ‐electrocyclization involving a keteniminium salt intermediate B , we are pleased to report herein the expansion of this method towards the facile synthesis of 3‐aminoindoles and 3‐aminobenzofurans E ( Scheme ) …”

Synthesis of Highly Substituted Cyclobutanones by a One‐Pot Keteniminium‐Enamine Process

“…The very reactive and electrophilic keteniminium salts are involved in a variety of chemical processes such as [2+2] cycloadditions, [1–3] electrocyclization, [4–9] Friedel–Crafts , [10,11] [1,5]‐hydride shift [12] and in amide umpolung, [13] among other examples [14–16] . The [2+2] cycloaddition between a keteniminium and an alkene partner is a very reliable method to generate four‐membered ring cycles, the resulting cyclobutaniminium salt being usually hydrolyzed into the cyclobutanone ( Scheme 1).…”