A Brønsted Acid Catalyzed Cascade Reaction for the Conversion of Indoles to α‐(3‐Indolyl) Ketones by Using 2‐Benzyloxy Aldehydes

Abstract

A Brønsted acid catalyzed, operationally simple, scalable route to several functionalized α‐(3‐indolyl) ketones has been developed and the long‐standing regioisomeric issue has been eliminated by choosing appropriate carbonyls. A readily available and cheap bottle reagent was used as the catalyst. This protocol was also applicable to the synthesis of densely functionalized α‐(3‐pyrrolyl) ketones. A detailed mechanistic study confirmed the involvement of enolether as a reaction intermediate. Several postsynthetic modifications along with easy access to β‐carboline, tryptamines, tryptophols, and spiro‐indolenine proclaim the synthetic utility of this powerful building block. On the basis of this concept, functionalized carbazoles were constructed by a cascade annulation strategy.

N-heterocyclic carbene and photocatalyst-catalyzed rapid access to indole ketones via radical C(sp3)–H acylation

“…Indole moieties are privileged structures in pharmaceuticals and bioactive molecules. 1 In particular, α-(2- or 3-indolyl) ketones have attracted much attention due to their biological activities 2 as well as their ability to construct diverse synthetic or naturally occurring biologically active molecules and heterocycles, such as tryptamines, 3 tryptophols, 4 β- or γ-carbolines, 4 c ,5 caulerpin derivatives, 6 and carbazoles (Fig. 1a).…”

Towards bioresource-based aggregation-induced emission luminogens from lignin β-O-4 motifs as renewable resources

“…Employing carbazole as a core moiety, introducing two electron acceptor groups (i.e., benzoyl) into a carbazole scaffold might provide an efficient way for the preparation of A-D-A-type AIEgens. Moreover, extensive synthetic strategies of the functionalized carbazoles focus on intermolecular cross-coupling reactions between C-H/C-X bonds (X = halo, N, O, C, etc) 56 , oxidative intramolecular C-H/C-H cross coupling of prefunctionalized diarylamines 57 , the construction of a benzene ring upon substituted indoles through transition metal catalysis 58 or Brønsted acid catalysis 59 – 61 . However, most approaches suffer from the need of excess oxidants, multi-step reactions and the formation of non-renewable substrates, which raises atom economy and environmental concerns.…”

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].…”