Chemoselective γ‐Oxidation of β,γ‐Unsaturated Amides with TEMPO

Abstract

A chemoselective and robust protocol for the γ‐oxidation of β,γ‐unsaturated amides is reported. In this method, electrophilic amide activation, in a rare application to unsaturated amides, enables a regioselective reaction with TEMPO resulting in the title products. Radical cyclisation reactions and oxidation of the synthesised products highlight the synthetic utility of the products obtained.

TEMPO-mediated late stage photochemical hydroxylation of biaryl sulfonium salts

“…TEMPO is already known as an oxidant 28–34 as well as a radical scavenger. 35–39 Nevertheless, its use as a hydroxyl source for the synthesis of phenols is to our knowledge unprecedented. The key to this approach is the UV-light, which can disrupt the C–S bond to form thianthrene radical cations and aryl radicals.…”

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

“…Since the seminal work of Viehe [25] and Ghosez , [26,27] KI salts have been most often used as highly reactive partners in [2+2] cycloaddition reactions with elegant applications in total syntheses [28–31] and methodologies, [32–39] but in the last decade new reaction types have emerged, relying on the high electrophilicity of these fascinating intermediates. 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).…”

“…Their propensity to react with even weak nucleophiles has been indeed harnessed for the synthesis of lactones, [40] heterocycles [41 -43] and 1,4dicarbonyls [44] as well as for the α and β functionalization of amides. [45][46][47][48][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.…”

Tf2O/TTBP (2,4,6-Tri-tert-butylpyrimidine): An Alternative Amide Activation System for the Direct Transformations of Both Tertiary and Secondary Amides

“…Forty years ago, the pioneering work of Ghosez et al on the [2 + 2] cycloaddition of alkenes with keteniminium salts, generated in situ from tertiary amides and triflic anhydride (Tf 2 O), , started off the modern amide chemistry . Owing to the continuing efforts of Charette et al., Movassaghi et al, Maulide et al, Huang et al, and others, the direct transformation of amides based on activation with Tf 2 O has become an active area of research, which has resulted in many useful synthetic methods and found synthetic applications. ,,, The base employed in partner with Tf 2 O to ensure effective activation and reaction of amides experienced an evolution from collidine , to Hünig base and to non-nucleophilic pyridine derivative DTBMP . The Tf 2 O/DTBMP combination was first introduced by Stang and Treptow for the transformation of ketones into vinyl triflates .…”