Synthesis of Indolo[2,1-a]isoquinolines by Nickel-Catalyzed Mizoroki–Heck/Amination Cascade Reaction

Abstract

An efficient Mizoroki−Heck/amination cascade reaction of o-dihaloarenes with cyclic imines was realized by combining nickel and a sterically bulky N-heterocyclic carbene ligand. This protocol provides access to a variety of indole[2,1a]isoquinolines from readily available starting materials. This cascade approach could be applied to produce straightforward synthesis of the natural product cryptowoline. Letter pubs.acs.org/OrgLett

Pseudo Four-Component Synthesis of 5,6-Dihydroindolo[2,1-a]isoquinolines

“…14 Furthermore, a recent paper by Xu Tian group described the synthesis of indolo [2,1-a] nickel and a bulky N-heterocyclic carbene ligand was used as a catalyst. 15 5,6-Dihydroindoloisoquinolines containing ester groups were synthesized via gold-catalyzed annulation of N-(oalkynylphenyl)imines with α-diazo esters. The reaction proceeds through the formation of cis-aziridine intermediates and subsequent cascade cyclization through the opening of the aziridine ring.…”

“…Furthermore, a recent paper by Xu Tian group described the synthesis of indolo­[2,1- a ]­isoquinolines through a cascade reaction of Mizoroki–Heck/amination of o -dihalogenarenes and 1-methyl-3,4-dihydroisoquinolines. A combination of nickel and a bulky N -heterocyclic carbene ligand was used as a catalyst …”

Palladium-Catalyzed Allylation of Endocyclic 1-Azaallyl Anions

“…Endocyclic 1-azaallyl anions (metalloenamines), species that had rarely been studied in a synthetic context due to inherent ring strain, ambident nucleophilicity, as well as lack of convenient methods for preparation, are the key intermediates . To expand the synthetic utility of these elusive intermediates as synthons to access β-C–H bond functionalized cyclic amines, we and Seidel recently reported the first transition-metal-catalyzed cross-coupling reaction between endocyclic 1-azaallyl anions and (aza)­aryl halides for the synthesis of unprotected cis -2,3-diarylpiperidines, along with an enantioselective variant using (2 R ,3 R )- i Pr-BI-DIME as the ligand. , As part of our continuous efforts to employ endocyclic 1-azaallyl anions in transition-metal-catalyzed cross-coupling reactions, we are now trying to develop an allylation of these species. The allyl group can then be readily transformed to a variety of functional groups, which dramatically increases the molecular diversity our approach accesses.…”

Rh(III)-Catalyzed Reaction of 4-Diazoisochroman-3-imines with (2-Formylaryl)boronic Acids To Access a Straightforward Construction of 5H-Isochromeno[3,4-c]isoquinolines

“…4 Because of their high reactivity, they initiate cascade sequences that lead to the generation of complex structural molecules of biological interest. 5 However, the strategies based on diazo chemistry have rarely been documented for the construction of isoquinoline-fused polycyclic systems. 6 In 2017, we developed a practical method for the convenient preparation of 4-diazoisochroman-3-imines.…”