Direct Access to Trifluoromethylated Benzo[d]oxepines from o-Alkynylaryl Aldehydes and Trifluorodiazoethane

Abstract

Reported in this Letter is a silver-catalyzed reaction between o-alkynylaryl aldehydes and trifluorodiazoethane that enables an expedient synthesis of trifluoromethylated benzo [d]oxepines. The reaction works through a silver-promoted 6-endo-dig cyclization of o-alkynylbenzaldehydes for the generation of an isochromenylium intermediate, which upon a ring-expansive addition of trifluorodiazoethane delivers a novel class of trifluoromethylated benzoxepine frameworks. This strategy was applied to the synthesis of phosphonylated benzo[d]oxepines using the Seyferth−Gilbert reagent.

Transition‐Metal‐Catalyzed Reactions Involving Trifluoro Diazo Compounds and Their Surrogates

“…Moreover, the utility of this strategy was also verified by its potential further synthetic applications in various synthetically and medicinally relevant molecules. Later, the Ag-catalyzed direct access to trifluorome-thylated benzo[d]oxepines [22] and benzo[d]azepines [23] from trifluorodiazoethane with o-alkynylaryl aldehydes, as well as alkynylaryl aldehydes and amines, were reported in 2023, respectively (Scheme 5b and 5c).…”

Gold-Catalyzed Reactions of Enynals with Alkenes for Synthesis Binaphthyl Derivatives

“…Because enynals are easily activated by Lewis acid or diverse transition metal catalysts, they were usually used for constructing naphthalene derivatives and other polycyclic skeletons . In 2003, Yamamoto and co-workers presented a practical protocol for the synthesis of 1,2-dihydronaphthalene, by using enynals and olefins as the reaction substrates, in the presence of Cu­(OTf) 2 (Scheme b) .…”

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

“…Fluoroalkyldiazo compounds belong to the most versatile and valuable reagents in organic synthesis, as they can be used as diazo intermediates or carbene precursors for the rapid construction of complex molecules along with the introduction of fluoroalkyl groups [14][15][16]. Although the reaction of trifluorodiazoethane [17][18][19][20][21][22][23][24][25][26][27] as well as α-diazo esters [28][29][30] have been widely explored, β-trifluoromethyl β-diazo esters have been less investigated, mainly due to the instability of such structures. Therefore, methods for the synthesis of β-trifluoromethyl β-diazo esters and their applications in organic synthesis are needed but remain challenging.…”