Solvent‐Controlled Bifurcated Cascade Process for the Selective Preparation of Dihydrocarbazoles or Dihydropyridoindoles

Abstract

A solvent-controlled cascade process has been identified for the dual purpose of the preparation of either dihydrocarbazoles or dihydropyridoindoles from identical N-aryl-α,β-unsaturated nitrones and electron-deficient allene starting materials. These reactions proceed smoothly under mild metal-free conditions affording a range of two types of skeletally distinct indole-based heterocycles in high yield and diastereoselectivity. These transformations demonstrate the use of a bifurcated cascade process that hinges on the ring-opening event of a benzazepine intermediate for the synthesis of skeletally diverse heterocyclic products and rapid access to biologically-significant, indole-based structures.

Catalytic Asymmetric Synthesis of Dihydropyrido[1,2‐a]indoles from Nitrones and Allenoates

“…A mixture of 8 a and benzazepine 9 a was generated in the absence of a catalyst when 1 a and 2 a were mixed at ambient temperature in isopropyl acetate. [2] This mixture was then transferred to C 6 F 5 H and exposed to catalyst 5 b. When a 5:1 mixture of 8 a and 9 a was treated with catalyst 5 b under the optimal reaction conditions (Scheme 4 B), the results were consistent with those observed when a mixture of 1 a and 2 a was exposed to catalyst 5 b under identical conditions.…”

“…[2] These examples serve to illustrate the appealing versatility of these types of cascade reactions for the preparation of heterocycles, as well as the challenges associated with controlling these processes, which are highly sensitive to reaction conditions and substituent effects.…”

“…[2] The treatment of a mixture of 1 a and 2 a with thiourea 5 a (10 mol %) at 60 8C provided 3 a in 12 % yield with poor enantioselectivity as a mixture with heterocycle 6 a ( Table 1, entry 1). [5] Elevation of the reaction temperature did not increase the yield of 3 a.…”

De novo branching cascades for structural and functional diversity in small molecules

“…N-phenyl nitrones (1) undergo [3 þ 2] cycloadditions with allenic esters (2) and the corresponding isoxazolidines (3) follow a pericyclic rearrangement leading to azepinones (5, Fig. 2) [30][31][32][33][34] . Azepinone 5 beholds different reactive functionalities like a secondary amine and a bketoester that can be exploited in branching cascade approach to build distinct azaheterocyclic frameworks.…”

Exploiting the Distal Reactivity of Indolyl Methylenemalononitriles: An Asymmetric Organocatalyzed [4+2] Cycloaddition with Enals Enables the Assembly of Elusive Dihydrocarbazoles

“…[1] Accordingly,t he search fore fficient methods for the assembly of these structuresh as drawn ag reat deal of attention in the synthetic organic chemistry community. [2,3] In 2011, Melchiorre [4] devised ar eliable synthetic platform to access tetrahydrocarbazoles by adopting a [ 4 + +2] strategy, which relies on in situ generation of active indole ortho-quinodimethane intermediates in reactions with suitable dienophiles (e.g.,n itrostyrene or indolinoned erivatives) under trienamine catalysis (Scheme 1A). More recently,o ur research group [5] discoveredadirect [4+ +2] eliminative cycloaddition strategy to access carbocycles with embedded fused cyclohexadiene frames.…”