Copper Promoted Oxidative Coupling of SnAP Hydrazines and Aldehydes to Form Chiral 1,4,5‐Oxadiazepanes and 1,2,5‐Triazepanes

Abstract

SnAP (Sn (tin) amine protocol) hydrazine reagents and aldehydes undergo oxidative, copper mediated coupling to form substituted 1,4,5‐oxadiazepanes and 1,2,5‐triazepanes. Unlike all prior reactions involving SnAP reagents, the SnAP hydrazine reagents undergo a molecular oxygen‐assisted oxidative cyclization. The air‐ and moisture tolerant transformation accommodates a broad range of groups including electron‐rich, electron‐poor aromatic, heteroaromatic, and aliphatic aldehydes and is amenable to gram scale synthesis. These unusual, chiral heterocycles have unexpectedly large optical rotations, which may find use in optical materials.

Accessing Illusive E Isomers of α-Ester Hydrazones via Visible-Light-Induced Pd-Catalyzed Heck-Type Alkylation

“…Alternatively, the CN double bond could be preserved via the radical addition/elimination strategy used in closely related oxime-type substrates; however, this route has not been realized for hydrazones. As a result, at this point, there are only few non-fluorinated radical examples present in the literature, which means that, even though oxidative C–H alkylation is possible, it remains quite limited in the choice of radical precursors to date. In addition, these reactions most often rely on use of dialkyl-substituted hydrazones, which may prevent further functionalization, such as employment in indole synthesis . A non-radical C–H alkylation/arylation pathway is also possible, usually via pseudo-enolate-type reactions, but these examples are scarce and limited to very specific systems .…”

Radical N2-Retention Cyclizations of Aryl Diazoniums: Access to 7/8/9-Membered Heterocycles

“…To date, reported approaches to triazepine compounds mainly focused on decarboxylative [4 + 3] annulation of benzoxazinanones with azomethine imines (Figure 1a, 1), 5 alkylation strategies employing hydrazines and hydroxylamines (Figure 1a, 2), 6 and metal-promoted intramolecular coupling of tributylstannyl hydrazones (Figure 1a, 3). 7 Nevertheless, these reported strategies for triazepines either need harsh reaction conditions or involve multiple steps and complex starting materials with a limited substrate scope. Despite significant advancements having been made in the research of synthesizing triazepines, there is still a demand to develop methods to generate highly functionalized triazepines, especially in terms of reactional diversity, applicability, and practicality.…”

“…To date, reported approaches to triazepine compounds mainly focused on decarboxylative [4 + 3] annulation of benzoxazinanones with azomethine imines (Figure a, 1), alkylation strategies employing hydrazines and hydroxylamines (Figure a, 2), and metal-promoted intramolecular coupling of tributylstannyl hydrazones (Figure a, 3) . Nevertheless, these reported strategies for triazepines either need harsh reaction conditions or involve multiple steps and complex starting materials with a limited substrate scope.…”