The Fascinating Chemistry of α‐Haloamides

Abstract

The aim of this review is to highlight the rich chemistry of α‐haloamides originally mainly used to discover new C−N, C−O and C−S bond forming reactions, and later widely employed in C−C cross‐coupling reactions with C(sp3), C(sp2) and C(sp) coupling partners. Radical‐mediated transformations of α‐haloamides bearing a suitable located unsaturated bond has proven to be a straightforward alternative to access diverse cyclic compounds by means of either radical initiators, transition metal redox catalysis or visible light photoredox catalysis. On the other hand, cycloadditions with α‐halohydroxamate‐based azaoxyallyl cations have garnered significant attention. Moreover, in view of the important role in life and materials science of difluoroalkylated compounds, a wide range of catalysts has been developed for the efficient incorporation of difluoroacetamido moieties into activated as well as unactivated substrates.

Diastereoselective [3 + 1] Cyclization Reaction of Oxindolyl Azaoxyallyl Cations with Sulfur Ylides: Assembly of 3,3′-Spiro[β-lactam]-oxindoles

“…Azaoxyallyl cations, generated from α-halo hydroxamates, have emerged as a highly reactive three-atomic synthon for preparing structurally diverse lactam heterocycles . In 2011, Jeffrey and coworkers reported the first synthetic application of azaoxyallyl cations in [4 + 3] cycloadditions by using furan or cyclopentadiene, and they also provided experimental evidence to demonstrate the existence of this transient intermediate .…”

“…Then, the model reaction of 1a and sulfonium salt 2a was investigated under alkaline conditions at room temperature. As illustrated in Table , hexafluoroisopropanol could not promote this reaction, despite the fact that it was frequently utilized as a privileged solvent because of its ability to stabilize the highly reactive azaoxyallyl cations (entry 1). − A poor conversion rate was still observed by using K 2 CO 3 as the base in various solvents (entries 2–5). To our delight, the target [3 + 1] annulation could be triggered with Cs 2 CO 3 , which diastereoselectively offered the desired product 3a in 58% isolated yield within a short time (entry 6).…”

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

“…The Diels-Alder reaction can also be used for the preparation of functionalized γ-lactams in a single step [55]. Radical 5-exo or 5-endo cyclizations of substituted N-allyl or N-vinyl α-halo amides VIII [56][57][58][59][60][61] or X [62][63][64][65][66] using atom transfer and other chain reactions, as well as non-chain methods [67][68][69][70][71][72][73] have been used to approach diverse γ-lactam-containing skeletons of the general structure IX or XI, respectively (Scheme 1A).…”

Synthetic Routes Towards the Synthesis of Geminal α‐Difunctionalized Ketones

“…Further to this, we would like to highlight to the readership that reviews focusing on the fluorination of ketones, [6] borylation of esters to access functionalised ketones, [7] methods for the synthesis of α‐acyloxy ketones, [8] α‐functionalized ketones from visible‐light promoted additions to alkenes, [9] α‐functionalized ketones from β‐keto acids, [10] selective α‐bromination of aryl carbonyl compounds, [11] application of sulfoxonium ylides to access α‐cyclopropyl and α‐dihydropyrazole ketones, [12] the trifunctionailization of alkynes to obtain functionalized ketones, [13] and the chemistry of α‐haloamides to generate new C−X bonds (X=N, O and S), [14] have recently been published and are an excellent supplement to this account.…”