Mild, Metal-Free Oxidative Ring-Expansion Approach for the Synthesis of Benzo[b]azepines

Abstract

Benzo[b]azepines are important structural motifs for the pharmaceutical industry. However, their syntheses are usually lengthy, involving several steps, transition-metal catalysts, and/or harsh conditions. A novel, general, mild, and metal-free oxidative ring expansion tandem reaction of hydroquinolines with TMSCHN 2 as a versatile soft nucleophile to gain access to these valuable compounds in a simple and straightforward manner is presented.

I2‐Promoted Intramolecular Oxidative Cyclization of Butenyl Anilines: A Facile Route to Benzo[b]azepines

“…Recent years, a series of [ m + n ] cycloadditions have emerged as versatile methods to access various benzo[ b ]azepines [9] . Besides these methods, benzo[ b ]azepine skeletons could be assembled through intramolecular cross‐coupling reactions, [10a–d] photocatalytic radical reactions, [10e] ring expansion reactions, [10f–g] and others [10h–k] . For instance, Wang [11] developed a method for the construction of benzo[ b ]azepines via copper‐catalyzed oxidative C( sp 3 )−H/C( sp 2 )−H cross‐coupling (Scheme 1a).…”

Iodine(III)‐Promoted Ring Expansion Reactions: A Metal‐Free Approach toward Seven‐Membered Heterocyclic Rings

“…Most of these methods require harsh conditions, costly catalysts, and multiple‐step synthetic procedures while having limited functional group tolerance [27] Furthermore, some of these strategies are mainly based on metal‐catalyzed intramolecular cyclization.…”

“…[12] To overcome the barriers and challenges related to the synthesis of seven-membered cyclic derivatives, some creative strategies have been developed, such as ring-closing metathesis, [13][14][15] cycloaddition reactions [16,17] of [4 + 3], [18][19][20][21] [5 + 2] [18] and [4 + 2 + 1], [22] Heck coupling, [23] radical additions, [24] intramolecular α-alkenylation of furans, [25] and others. [26][27][28][29][30][31] Most of these methods require harsh conditions, costly catalysts, and multiple-step synthetic procedures while having limited functional group tolerance [27] Furthermore, some of these strategies are mainly based on metal-catalyzed intramolecular cyclization.…”

“…The construction of a seven‐membered ring skeleton is more challenging than the synthesis of five‐ or six‐membered rings, due to entropic factors and unfavorable transannular interactions [12] . To overcome the barriers and challenges related to the synthesis of seven‐membered cyclic derivatives, some creative strategies have been developed, such as ring‐closing metathesis, [13–15] cycloaddition reactions [16,17] of [4+3], [18–21] [5+2] [18] and [4+2+1], [22] Heck coupling, [23] radical additions, [24] intramolecular α‐alkenylation of furans, [25] and others [26–31] …”

Synthesis of cyclic aza-peroxides (microreview)

“…Several obtained endoperoxides are valuable precursors for the synthesis of d -fused 1-benzazepines with antitumor activity. 12 …”