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

Abstract

Herein, we describe a high yielding approach towards the synthesis of 3-amino-indoles and -benzofurans through 6π-electrocyclization. This was made possible by taking advantage of the high reactivity of keteniminium salts, formed in-situ by treating with triflic anhydride and 2-fluoropyridine amides bearing at the α-position either an aniline or a phenoxy moiety. These mild conditions, on top of furnishing rapidly the 3aminobenzoheteroles, allow the tolerance of various functional groups. Control experiments were carried out to highlight that the keteniminium is, indeed, in most cases, the reactive intermediate and conformational preferences of such species were investigated through a DFT study.

Efficient Synthesis of 9‐Aminophenanthrenes and Heterocyclic Analogues by Electrocyclization of Biaryl Keteniminium Salts

“…The reactivity of the distal phenyl is then itself surpassed by the vinyl moiety in 27 , with again a full selectivity towards the formation of aminonaphthalene 29 . Finally, the aryloxy substituents adequately placed in 30 and 33 give the possibility to form benzofurans 32 and 35 , respectively [54] . To our surprise, compound 30 leads exclusively to phenanthrene 31 despite the electron‐rich phenoxy group.…”

“…The next step consisted in exploring the substitution pattern of the two phenyl rings ( Scheme 4), keeping in mind that removing electron density from the π system of the distal phenyl ring should slow down the rate of electrocyclization as already reported in analogous reactions [54] . We were pleased to see that 7a and 7b , substituted on the proximal ring (substituent R 2 ) para to the KI by a methoxy and a cyano group respectively, furnished both excellent yields of 8a and 8b (86 % and 99 % resp.).…”

“…Their propensity to react with even weak nucleophiles has been indeed harnessed for the synthesis of lactones, [40] heterocycles [41–43] and 1,4‐dicarbonyls [44] as well as for the α and β functionalization of amides [45–49] . Besides, our group has investigated the remarkable ability of KI intermediates to undergo electrocyclization reactions, giving rise to efficient syntheses of amino‐naphthalenes, [50] 3‐aminobenzothiopene, [51,52] 3‐aminothiophenes, [53] 3‐aminoindoles and 3‐aminobenzofuran [54] ( Scheme 1). Recent thorough computational studies have deciphered the nature and the mechanistic aspects of these pericyclic reactions [55] …”

One‐Pot Three‐Component Synthesis of 2‐Methyl‐3‐aminobenzofurans Using Calcium Carbide as a Concise Solid Alkyne Source

“…Only few literatures reported the synthesis of 2‐substituted 3‐aminobenzofurans, which include i) copper‐catalyzed annulative amination of o ‐alkynylphenols with hydroxylamines; [ 6 ] ii) three‐component coupling reactions of alkynylsilanes, o ‐hydroxybenzaldehydes, and secondary amines by Cu(I)/Cu(II) cooperative catalytic systems; [ 7 ] iii) treatment of amides bearing an α‐phenoxy moiety with triflic anhydride and 2‐fluoropyridine (Scheme 1). [ 8 ] However, some methods utilize commercially unavailable substrates as starting materials, which have to synthesize through many steps. Meanwhile, unstable, expensive and difficult‐ to‐handle alkyne sources have to be applied, which generally need to synthesize using inflammable and explosive acetylene gas as an original alkyne source.…”

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).…”