CuCN-Mediated O-Alkylation of N,N,-Dimethylformamide with Alkyl Halides

Abstract

This article reports the CuCN-mediated O-alkylation of formamide with 2-bromomethylindole. In addition, the formyloxylation products have been successfully exploited in the synthesis of novel indol-2-ylmethyl ether derivatives.

Vilsmeier–Haack reagent-promoted formyloxylation of α-chloro-N-arylacetamides by formamide

“…Employing 1.0, 2.0 and 3.0 equivalents of PBr 3 to the reaction increased the yields of 4 to 84, 88, and 96%, respectively (entries [4][5][6]. In these cases, a trace amount of hydrolyzed product 5 was observed.…”

“…al reported the CuCN-mediated O-alkylation of DMF at room temperature. 6 α-Formyloxy carbonyl compounds are important intermediates 7 for the construction of various heterocyclic compounds such as imidazopyrimidine-2,7-diones 8 and oxazoles. 9 α-Haloketones are also reported formyloxylated by formamides in the presence of copper catalyst 10 or Silphos agent [PCl 3 -n (SiO 2 ) n ].…”

“…For example, Dakanali et al reported the formyloxylation of 2-bromoethylamines by DMF at 80 C through the participation of neighboring group, 4 Abad et al reported the use of silver salt as the catalyst to furnish the reaction at r.t. to 75 C, 5 and Thirumamagal et al reported the CuCN-mediated O-alkylation of DMF at room temperature. 6 a-Formyloxy carbonyl compounds are important intermediates 7 for the construction of various heterocyclic compounds such as imidazopyrimidine-2,7-diones 8 and oxazoles. 9 a-Haloketones are also reported formyloxylated by formamides in the presence of copper catalyst 10 or silphos agent [PCl 3Àn (SiO 2 ) n ].…”