Copper-Catalyzed Difluoroalkylation of Alkene/Nitrile Insertion/Cyclization Tandem Sequences: Construction of Difluorinated Bicyclic Amidines

Abstract

A copper-catalyzed difluoroalkylation of an alkene/nitrile insertion/cyclization tandem sequence of N-cyanamide alkene was described, which provided a convenient synthetic approach for accessing difluorinated bicyclic amidines bearing imine moieties in a sustainable fashion. This protocol is characterized by high yields, a broad substrate scope, and good functional group compatibility. In addition, the desired product can be readily converted into other valuable functionalized fluorinated aza-heterocycles.B icyclic amidine moieties (partially saturated pyrrolo [2,3b]pyridine or 1,8-naphthyridine) have been found in a series of natural alkaloids such as perophoramidine, communesins, and dehydronitraramine, 1a−d bioactive molecules [(S)-Blebbistatin], 1e amidine bases, acceptors of molecular recognitions etc. (Figure 1). 1f−h However, a few synthetic Letter pubs.acs.org/OrgLett

Assembly of tetracyclic tetrahydrocarbazoles via a visible-light promoted cascade process

“…According to the above experimental results and the previous reports, 10,14 To demonstrate the synthetic utility of this protocol, the large-scale application of this reaction was carried out (Scheme 6a). A reaction with the scale enlarged from 0.1 mmol to 3.0 mmol was conducted, which proceeded smoothly to furnish the corresponding product 3aa in 65% yield after 3 h. Also, the obtained canthin-6-one analog 3aa could be converted into the corresponding alcohol 6 via treatment with NaBH 4 and trifluoroacetic acid under reflux (Scheme 6b).…”

“…13 In particular, the ester group of bromodifluoro- acetates could be substituted by nucleophilic species at a suitable position on the in situ generated intermediate to construct complex heterocycles. 14 Inspired by these elegant works, 11,12,14 we tried to incorporate such a useful fluorinated skeleton into the indole tethered alkenes to provide a new approach for the rapid assembly of fused tetracyclic tetrahydrocarbazole-based compounds. Herein, we report an interesting visible-light promoted cascade reaction of indole tethered alkenes with bromodifluoroacetates as difluoroacetylation reagents, which affords fluorinated tetracyclic tetrahydrocarbazoles as the products (Scheme 1d).…”

Synthesis of imidazo[1,2-a]pyridinones via a visible light-photocatalyzed functionalization of alkynes/nitrile insertion/cyclization tandem sequence using micro-flow technology

“…On the basis of these studies, control experiments, and previous reports, 30,[35][36][37][38][39] a plausible mechanism was proposed (Scheme 6). First, the organic photocatalyst PC-B was exposed to visible light to form an excited state PC-B*.…”

Copper-Catalyzed Difluoroalkylation Reaction

“…Difluoroalkylation of an olefin/nitrile insertion/cyclization tandem sequence of N-cyanamide olefins catalyzed by copper was realized by Liao’s group, which provides a convenient synthesis method for obtaining difluorobicycloamides containing imine groups in a sustainable manner ( Scheme 8 ) [ 42 ]. The protocol has the advantages of a high yield, wide substrate range and good functional group compatibility.…”