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

Abstract

An unprecedented technique for the in situ generation of indolyl ortho-quinodimethanes from 2-methylindole-based methylenemalononitriles by amine-mediated remote C(sp(3) )-H deprotonation was developed. These intermediates were efficiently trapped by diverse enals to provide a rapid entry to 2,9-dihydro-1H-carbazole-3-carboxyaldehyde structures through a formal asymmetric [4+2] eliminative cycloaddition governed by a α,α-diphenylprolinol trimethylsilyl ether catalyst.

Carbene-Catalyzed Reaction of Indolyl Methylenemalononitriles and Enals for Access to Complex Tetrahydrocarbazoles

“…In recent years, enantioselective catalytic access to chiral hydrocarbazoles and their derivatives via transition-metal-free approaches have received considerable attention . Most of the success in this regard relies on the use of chiral amine catalysts to activate one of the reaction partners via iminium or enamine catalytic pathways, as disclosed by the groups of MacMillan, Melchiorre, Chen, Zanardi, and others . A potentially efficient approach to make this class of molecules is functionalization of indole derivatives .…”

Copper-catalyzed multicomponent reactions for the efficient synthesis of diverse spirotetrahydrocarbazoles

“…Therefore, many [4 + 2] reactions of 3-vinylindolines or 2-vinylindolines with diverse dienophiles have been successfully developed for the synthesis of many tetrahydrocarbazole and carbazole derivatives . On the other hand, the Diels-Alder reaction of the in situ generated indole-2,3-quinodimethanes with various dienophiles is also a powerful method for rapid construction of functionalized tetrahydrocarbazoles [51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68]. In this respect, Lévy reported a copper-catalyzed three-component reaction of aromatic aldehydes, ethyl indole-2-acetate and N-alkylmaleimides for the efficient construction of polycyclic tetrahydrocarbazoles, in which indolo-2,3-quinodimethane intermediate was initially generated and sequentially underwent a [4 + 2] cycloaddition reaction (reaction 1 in Scheme 1) [69][70][71][72][73][74].…”

Unlocking Access to Enantiopure Fused Uracils by Chemodivergent [4+2] Cross‐Cycloadditions: DFT‐Supported Homo‐Synergistic Organocatalytic Approach

“…In that instance,astrategic escamotage was devised, to temporarily activate the donor carbaldehyde chemoselectively as am ethylenemalonate derivative V,t ot rigger the intended [4+ +2] coupling between the in situ activated components V' ' and VI' '.T he spontaneous malononitrile elimination finally provided the g,ipso-locked cyclohexene aldehyde products VII in ag lobal eliminative [4+ +2] cycloaddition reaction. [10] In the third example [Scheme 1, Eq. 3],t he crosscoupling between ortho-tolualdehyde VIII and enals VI could be feasible by installing electron-withdrawing groups in the donor component (i.e.n itro groups).…”