Intermolecular and Regioselective Access to Polysubstituted Benzo‐ and Dihydrobenzo[c]azepine Derivatives: Modulating the Reactivity of Group 6 Non‐Heteroatom‐Stabilized Alkynyl Carbene Complexes

Abstract

We highlight the versatility of non-heteroatom-stabilized tungsten-carbene complexes 3 synthesized in situ, which have been used in a modular approach to access 2-benzazepinium isolable intermediates 5. By employing very mild conditions, benzazepinium derivatives 5 have been obtained in high yield from simple compounds, such as acetylides 2, Fischer-type alkoxycarbenes 1, and phenylimines 4. The process, involving a formal [4+3] heterocycloaddition, occurs in a totally regioselective manner, which differs from the approach previously observed in similar procedures for other carbene analogues. This work, which involves three components, reveals a control of the reactivity of non-heteroatom-stabilized carbene complexes 3 ([4+3] vs. [2+2]-heterocycloaddition reactions) depending on the acetylide substitution pattern. The influence of the substitution pattern in the behavior of the complexes has been computationally analyzed and rationalized. Finally, elaboration of the 2-benzazepinium intermediates allows access to 3H-benzo[c]azepines 6 and 3H-1,2-dihydrobenzo[c]azepines 7-9 with high control of the substitution of the nine positions of the heterocycle.

Understanding the Mechanism of the Divergent Reactivity of Non-Heteroatom-Stabilized Chromium Carbene Complexes with Furfural Imines: Formation of Benzofurans and Azetines

“…Once intermediate I is formed, a cyclization process could allow for the formation of 6b . A similar transformation has been previously reported . The transition structure leading to this transformation is 17.7 kcal/mol above the reactants, clearly above the 11.5 kcal/mol energy barrier leading to the formation of the benzofurans (see Figure ).…”

“…An energy barrier of 20.1 kcal/mol was found for this step, and II is located 8.4 kcal/mol below the initial reactants (see Figure ). This type of cyclization is related to similar processes recently reported …”

“…Accordingly, these compounds are able to form open chain policonjugated compounds as endiynes or linear dienynes or diendiynes and also to participate in different cyclizations with the formation of three to seven-membered rings. Thus, non-heteroatom-stabilized alkynylcarbenes react with olefins to form cyclopropanes or with imines to access stable azetinylcarbenes or benzoazepines through formal [2 + 2] and [4 + 3] heterocyclizations, respectively. Finally, a formal [3 + 3] benzofuran synthesis from furylimines has also been reported .…”

Fischer Carbene Complexes: A Glance at Two Decades of Research on Higher‐Order Cycloaddition Reactions

“…Based on DFT calculations, the proposed mechanism is an attack of the imine on the C β of the carbene complex 224 to give allenyl metallate 227 . The latter compound is transformed into intermediate 228 through a cyclization entailing a [1,2] metal shift, and the synthesis of azepines derivatives 226 is completed by means of a [1,5]‐hydrogen migration and subsequent re‐aromatization (Scheme 39B) [168] …”

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

“…574, Scheme 39) lacking heteroatoms and benzaldehyde imines led to net [4+3] cycloaddition products (e.g. 578)[928]. The alkynylcarbene complexes were generated at low temperature through the reaction of alkoxycarbene complexes (e.g.…”