Ag^I‐Promoted Difluoromethylation of Isocyanides To Give Difluoromethylated Phenanthridines

Abstract

An AgI‐mediated ethoxycarbonyldifluoromethylation of isocyanides has been developed. This radical cascade reaction involves the addition of difluoromethylene radical to the isocyanide functionality, and subsequent homolytic aromatic substitution to give difluoromethylated phenanthridines with a good functional‐group tolerance.

Crafting mono- and novel bis-methylated pyrroloquinoxaline derivatives from a shared precursor and its application in the total synthesis of marinoquinoline A

“…Notably, a minor amount of an unexpected bis-methylated pyrroloquinoxaline 6a was also obtained in a yield of 10% (entry 2); 30 this is similar to the difluoromethyl radical addition reported previously in the 1 and 4 positions of a pyrroloquinoxaline. 20 When the sequential methylation and intramolecular aromatisation conditions employed by Dai were applied to aryl isocyanide 4a, pyrroloquinoxaline 5a was isolated in an encouraging 48% yield with no bis-methyl adduct 6a observed (entry 3). 31 Cyclisation with dicumyl peroxide (DCP) in the presence of KF in t -BuOH resulted in pyrroloquinoxaline 5a in 67% yield with 4% of 6a in the reaction mixture observed by 1 H-NMR (entry 4).…”

“…Wan et al observed a radical addition to form a bis-alkylated pyrroloquinoxaline. 20 This is proposed to occur via a direct C–H radical addition to the α-position of the pyrrole ring followed by a second radical addition to the isocyanide to form the α-imidoyl radical. This undergoes cyclisation followed by aromatisation to form the bis-alkylated pyrroloquinoxaline 6a.…”

“…18 Addition of alkyl groups have been recently reported to isocyanides to form 4-substituted pyrrolo[1,2-a]quinoxalines. [19][20][21][22][23][24][25] The methyl group is one of the most widespread functional groups in small biologically active molecules. Over the past decade, the methyl group has gained much interest in the pharmaceutical eld due to its ability to increase a drug's binding affinity and potency.…”

Recent Trends in the Synthesis and Mechanistic Implications of Phenanthridines

“…In the same year, Wan and group developed [44] a silver(I)‐catalyzed convenient synthetic route for the preparation of ethoxycarbonyldifluoromethylated phenanthridines 10 b . The ethoxycarbonyldifluoromethylation of isocyanides 8 in presence of TMSCF 2 CO 2 Et 143 via radical cascade process afforded various phenanthridine derivatives with high functional group compatibility.…”