The facile synthesis of 1-benzoazepine derivatives via gold-catalyzed regioselective cycloisomerization reactions of N-(o-alkynylaryl)-N-vinyl sulfonamides

Abstract

Gold-catalyzed, regioselective cycloisomerization of N-(o-alkynylaryl)-N-vinyl sulfonamides afforded high yields of 2-sulfonylmethyl-1-benzoazepine derivatives. This 7-endo-dig selective cyclization proceeds via the incorporation of an exocyclic double bond by a labile 1-benzoazepine intermediate. The cyclization substrates were assembled in two steps from readily available materials using Sonogashira coupling and a Cs2CO3-mediated formal vinylic substitution.

Homogeneous Gold Catalysis for Regioselective Carbocyclization of Alkynyl Precursors

“…Substrates with one carbon extension such as 3-aza-1,6enynes 2.9 delievers benzoazepine derivatives 2.10 under the catalytic action of Echavarren's gold(I)-complex (Scheme 11, eq 1). [115] As a rare observation, this class of substrates overrides the entropy favored 6-exo-dig mode and undergoes a 7-endo-Scheme 9. Au(I)-catalyzed regio-and stereoselective carbocyclization of alkynyl silyl enol ethers using chiral (eq 1) and bowl-shaped phosphine ligands (eq 2) Scheme 10.…”

“…Substrates with one carbon extension such as 3‐aza‐1,6‐enynes 2.9 delievers benzoazepine derivatives 2.10 under the catalytic action of Echavarren's gold(I)‐complex (Scheme 11, eq 1) [115] . As a rare observation, this class of substrates overrides the entropy favored 6‐ exo ‐ dig mode and undergoes a 7‐ endo ‐ dig carbocyclization ( 2.11 ).…”

Regio- and Diastereoselective Construction of Functionalized Benzo[b]oxepines and Benzo[b]azepines via Recyclable Gold(I)-Catalyzed Cyclizations

“…Pagar and Liu developed an efficient method for the assembly of benzo­[ b ]­azepine and isoxazolidine derivatives via Au-catalyzed cycloaddtion reactions of vinyldiazo carbonyl compounds, nitrosoarenes, and ethyl diazoacetate . Besides, Au-catalyzed intramolecular cyclizations of N -allenylamides, 2-tosylaminophenyl cyclopropylmethanols, 2-( N -(prop-2-ynyl)- N -tosylamino)­benzaldehydes, and N -( o -alkynylaryl)- N -vinyl sulfonamides have also been reported for the construction of benzo­[ b ]­azepine derivatives . Although these gold-catalyzed reactions are highly efficient for the assembly of benzo­[ b ]­oxepines and benzo­[ b ]­azepines, application of homogeneous gold complexes in large-scale synthesis or industry still remains an important challenge due to their exorbitant prices because they are difficult to recover from the reaction mixture and cannot be recycled.…”

Palladium‐Catalyzed Regioselective Synthesis of 1‐Benzoazepine Carbonitriles from o‐Alkynylanilines via 7‐endo‐dig Annulation and Cyanation

“…The 1‐benzoazepine scaffold has attracted less attention from the synthetic community than those of 2‐ and 3‐benzoazepines, even though compounds with this scaffold possess potential bioactivities . Very few elegant methods have been reported in the literature for synthesizing the 1‐benzoazepine core; however, transition‐metal‐catalyzed annulation reactions, ring openings of alkylidenecyclopropanes and isoxazolidines, cycloadditions, rearrangement reactions, and others have been reported .…”