Modular Access to Azepines by Directed Carbonylative C–C Bond Activation of Aminocyclopropanes

Abstract

A modular Rh-catalyzed entry to azepines is outlined. Under a CO atmosphere, protecting group directed C–C bond activation of aminocyclopropanes provides rhodacyclopentanones. These intermediates are effective for intramolecular C–H metalation of either an N-aryl or N-vinyl unit en route to azepine ring systems. Thus, byproduct-free heterocyclizations are enabled by sequential C–C activation and C–H functionalization steps.

Recent Advances in Transition‐Metal‐Catalyzed Oxidative Annulations to Benzazepines and Benzodiazepines

“…[41] In addition, a Rh-catalyzed (6 + 1) carbonylation of Ncyclopropylanilides (carbonylative CÀ C activation) rendered benzazepin-5-ones ( Figure 3). [42] One of the pioneering examples of multicomponent annulations was reported by Wang and co-workers in 2013. [35] They probed that isatins 1, a cyclic anilidetype substrate, can react with two equivalents of alkynes 2 to give 1-benzazepines 3 in a formal (3 + 2 + 2) cycloaddition (Scheme 1).…”

Synthesis of naphtho[1,2‐b]‐, naphtho[2,1‐b]‐, and naphtho[2,3‐b]azepinones via proton‐induced cyclization of N‐1(2)‐naphthyl styrylacetamides

“…Among the most widely used synthetic routes to naphtho[1,2‐ b ]azepine and naphtho[2,3‐ b ]azepine are the Beckmann rearrangement of the corresponding hydrogenated phenanthrenones and diverse intramolecular catalytic cyclizations of functionalized 1(2)‐aminonaphthalenes . Both approaches quite often suffer from certain limitations such as the need for hardly accessible reagents, multistep syntheses, the lack of selectivity, and low yields.…”

Synthesis of Bridged Tetrahydrobenzo[b]azepines and Derivatives through an Aza‐Piancatelli Cyclization/Michael Addition Sequence

“…Tetrahydrobenzo [b]azepines represent an important class of medium-size nitrogen heterocycles,w hose scaffolds can be found in various bioactive molecules,i ncluding tolvaptan, [1] benazepril, [2] and evacetrapib [3] (Scheme 1). Consequently, tremendous efforts have been recently dedicated to devise creative,e fficient, and flexible strategies to prepare these compounds, [4] while providing molecular complexity and diversity for applications in drug discovery.I nt his context, bridged tetrahydrobenzo [b]azepines remain an elusive subclass of this family,the development of which has been clearly underexplored. [5] Currently,o ne of the few applications of these compounds is to serve as intermediates for the synthesis of aza-rocaglate derivatives,which was reported by the group of Porco.…”