One-Pot Sonogashira Coupling–Cyclization toward Regioselective Synthesis of Benzosultams

Abstract

A one-pot method for the Sonogashira coupling and cyclization of 2-bromobenzenesulfonamides and terminal alkynes is presented. This method allows access to a variety of substituted benzosultams regioselectively in excellent yields. The reasons for regioselectivity are interpreted through density functional theory (DFT) studies.

Recent Advances in Catalytic Synthesis of Benzosultams

“…Transition metal-mediated hydroamination of alkyne provides a powerful platform for the formation of C–N bonds, which has found widespread applications in the synthesis of various biologically important heterocycles [ 85 , 86 ]. In 2015, Mondal and co-workers developed an elegant Pd/Cu-catalyzed one-pot Sonogashira coupling/hydroamination cascade of 2-bromobenzenesulfonamides with terminal alkynes, providing an alternative access to benzosultams [ 87 ]. In addition, Zhu et al finished the synthesis of a variety of indole-fused benzosultams via Pd(II)-catalyzed diamination of alkynes [ 88 ].…”

Sultams: Recent Syntheses and Applications

“…We have also reported Pd‐catalyzed one‐pot Sonogashira coupling and regioselective cyclization through hydroamination for the synthesis of benzo‐δ‐sultams 27.3 from commercially available 2‐bromobenzenesulfonamide derivatives 27.1 and terminal acetylenes 27.2 (Scheme ) . The reaction occurred by way of classic Sonogashira coupling followed by regioselective 6‐ endo ‐ dig cyclization.…”

“…We have also reported Pd-catalyzed one-pot Sonogashira coupling and regioselective cyclization through hydroamination for the synthesis of benzo-δ-sultams 27.3 from commercially available 2-bromobenzenesulfonamide derivatives 27.1 and terminal acetylenes 27.2 (Scheme 27). [28] The reaction occurred by way of classic Sonogashira coupling followed by regioselective 6-endo-dig cyclization. The proposed mechanism of the cyclization is similar to that proposed by Rao, Pal, et al In a recent communication, Zhou and co-workers reported the facile synthesis of various γ-, δ-, and ε-sultams through palladium-catalyzed enantioselective intramolecular asymmetric reductive amination of ketones with weakly nucleophilic sulfonamides (Scheme 28).…”

A Direct and an Efficient Regioselective Synthesis of 1,2-Benzothiazine 1,1-dioxides, β-Carbolinones, Indolo[2,3-c]pyran-1-ones, Indolo[3,2-c]pyran-1-ones, Thieno[2,3-c]pyran-7-ones and Pyrano[3’,4’:4,5]imidazo[1,2-a]pyridin-1-ones via Tandem Stille/Heterocyclization Reaction

“…Numerous ways to access these moieties are depicted in the literature. The most popular route used is metal catalyzed bond formation [17][18][19][20][21][22][23][24]. For example, β-carbolinones are accessed via Heck [15], gold cycloisomerization [25] or copper catalyzed C-N bond formation [26].…”