Regioselective N‐Functionalization of Tautomerizable Heterocycles through Methyl Trifluoromethanesulfonate‐Catalyzed Substitution of Alcohols and Alkyl Group Migrations

Abstract

A catalytic synthetic strategy has been developed combining two protocols, such as, direct nucleophilic substitution of alcohols followed by X‐ to N‐ alkyl group migration (X=O, S) to access N‐functionalized benzoxazolones, benzothiazolethiones, indolinone, benzoimidazolethiones, and pyridinones derivatives. Methyl trifluoromethanesulfonate (MeOTf) was found to catalyze the reaction, which revealed the catalytic property of MeOTf. A mechanism was established through experiments as well as DFT calculations wherein the −OH group of alcohols were converted to the corresponding −OMe groups and in situ generated TfOH. The −OMe groups produced underwent TfOH catalyzed −X alkylation (X=O, S) of the heterocycles followed by −X‐ to −N‐alkyl group migrations in a single step.

2‐Hydroxypyridines as N‐ and O‐Nucleophiles in Organic Synthesis

“…By combining two protocols, namely nucleophilic substitution of alcohols and O ‐ to N ‐alkyl group migration, Biswas and Morgon's group demonstrated MeOTf‐catalyzed N ‐alkylation of 2‐hydroxypyridines 1 with benzyl alcohol derivatives 2 (Scheme 2). [9] Various 2‐hydroxypyridines and benzyl alcohol derivatives displayed robust reactivity and compatibility with various functional groups. Notably, this elegant strategy was also suitable for the construction of N ‐alkyl substituted benzoxazolones, benzothiazolethiones, indolinones and benzoimidazolethiones.…”

Michael Addition Reaction of Benzothiazol‐2‐thiol/Benoxazol‐2‐thiol with α, β‐Unsaturated Esters: Chemoselective Construction of C−S and C−N Bonds

“…[16] Prior to this, our laboratory also realized the synthesis of benzoheterocyclo-2-sulfides via one-pot manner. [17] Besides, Bolm [18] and Biswasa [19] realized the construction of CÀ N bond using iodobenzene or alcohols react with nitrogencontaining heterocyclic compounds respectively. It is worth noting that Wang, Buchwald, Chen et al [20] achieved the chemoselective CÀ S/CÀ N coupling under different reaction conditions.…”

Solvent Effects in the Regioselective N-Functionalization of Tautomerizable Heterocycles Catalyzed by Methyl Trifluoromethanesulfonate: A Density Functional Theory Study with Implicit Solvent Model

“…The yield of the functionalization, using commercially available BrØnsted acids such as trifluoromethanesulfonic acid (TfOH), is solvent-dependent. The yield is equal to 80, 70, 48, 20, 0 and 23% in toluene, chloroform, dichloroethane, diisopropyl ether, acetonitrile and nitromethane, respectively [10]. To gain a further understanding of the solvent effects on the role of methyl trifluoromethanesulfonate (MeOTf), DFT calculations were performed through the study of the potential energy surface involving the cooperative effects of MeOTf for the formation of the products.…”