Recent Progress in Transition‐Metal‐Free, Base‐Mediated Benzannulation Reactions for the Synthesis of a Diverse Range of Aromatic and Heteroaromatic Compounds

Abstract

Benzene and itsderivativesare the most abundant substructures of several interesting classes of compound, such as bioactive molecules. Owing to their importance, the development of methods for their constructionh as attracted considerable attention.H owever,t he regioselectives ynthesis of polysubstituted aromatic and heteroaromatic compounds by using aromatic substitution is challenging, because it provides derivatives with restricted substitution patterns. Therefore, the benzannulation reaction-the assembly of benzene derivatives from acyclicp recursors-constitutes as uperior and highly versatile approach to polysubstituted aromatic and heteroaromatic compounds,a nd variouse fficient benzannulation reactions have been reported.R epresentative examples include Cs 2 CO 3 , t-BuOK,a nd DBU-catalyzed reactions for the construction of valuableb enzene derivatives. The central objective of this Focus Review is to highlight base-mediated benzannulation reactions under transitionmetal-free conditions for the construction of aromatic and heteroaromatic compounds.[a] Dr.Recently,P an and co-workers investigated the K 2 CO 3 -catalyzed cascade benzannulation reaction of b-keto sulfones 1 with acetylene ketones 2 by using 30 %m ol K 2 CO 3 without other additives,w hich afforded new sulfonylbenzene derivatives 3 in good yields through ab enzannulation reaction (Scheme 1a). [18] Av ariety of electron-donating ande lectron-withdrawing groups were well-tolerated under the optimized reaction conditions. The proposed reactionpathway proceeded through se-quentialM ichael addition, intramolecular cyclization, hydrogen abstraction, and dehydration reactions (Scheme 1b).Scheme55. Synthesis of unsymmetrical biaryls from the annulation/aromatizationr eactionsof1 ,4-pentanedienes with nitroalkanes.Scheme56. DBU-promoted [5+ +1] annulation reaction of a-alkenoyl ketene-S,S-acetalswith nitroalkanes.

Regioselective Synthesis of Arylsulfonyl Benzophenones via Aerobic Oxidative [3+3] Benzannulation Reactions

“…Benzannulation reactions, wherein acyclic precursors are assembled together to construct arene scaffolds, offer certain advantages over the conventional aromatic substitution reactions. [ 13 ] The major advantages of benzannulation method include; (i) a larger variety of reaction components to choose from, (ii) better scope for catalysts and (iii) the possibility of circumventing directing/deactivating effect of arene substituents. Recent studies in our group have led to the development of [3+3] benzannulation reactions for the construction of variously substituted arenes.…”

Recent Progress towards Organocatalyzed Asymmetric (Hetero)Arene Formation

“…20 Recently, a variety of base-mediated benzannulation reactions were developed for the efficient synthesis of (hetero)arenes and related non-chiral examples were well documented. 21 Similar to acid organocatalysis, the base-generated carbanion intermediate is likely to attach to the counter cation, hence the introduction of a chiral cation catalyst (e.g., an ammonium salt) may control the selectivity of the reaction.…”

Regioselective synthesis of benzonitriles via amino-catalyzed [3+3] benzannulation reaction

“…In recent years, benzannulation reaction, an assembly of readily available acyclic precursors into polysubstituted arenes, has received much attention due to its high efficiency, functional flexibility, and superior control of regiochemical outcome. 9,10 In this area, formation of benzonitrile cores relies largely on the rational integration of acyclic building blocks which bear one or more cyano groups into aromatic scaffolds. Hence, synthesis of benzannulated benzonitriles to a great extent avoids introducing toxic cyanide sources and provides much broader substrate scope.…”