Copper-Catalyzed Tertiary Alkylative Cyanation for the Synthesis of Cyanated Peptide Building Blocks

Abstract

In this paper, we report efficient cyanation of various peptides containing the α-bromocarbonyl moiety using a Cucatalyzed radical-based methodology employing zinc cyanide as the cyanide source. Mechanistic studies revealed that in situ formed CuCN was a key intermediate during the catalytic cycle. Our method could be useful for the synthesis of modified peptides containing quaternary carbons.

A boron–nitrogen transborylation enabled, borane-catalysed reductive cyanation of enones

“…19,20 Catalytic cyanation of a-bromo amides can be achieved with copper catalysis, however, this method is limited to sterically congested substrates. 21 Catalytic, non-metal methods for the synthesis of b-ketonitriles include the cyanation of silyl enol ethers 22 catalysed by B(C 6 F 5 ) 3 and amine-catalysed 23 reductive cyanation of b-keto esters and b-keto amides. However, a general strategy for main-group-catalysed cyanation without the requirement for pre-functionalised substrates would provide an advantage over existing methodologies.…”

Access to α-Cyano Carbonyls Bearing a Quaternary Carbon Center by Reductive Cyanation

“…As we know, only one elegant pathway to α-cyano carboxamides via copper-catalyzed cyanation of tertiary bromides with zinc cyanide was reported by Nishikata and Kuninobu recently. 9 Therefore, the reaction protocol, which can be simultaneously applicable for the synthesis of α-cyano ketones, esters, and carboxamides bearing a quaternary center, has yet to be established. Considering the thriving progress on oxidative cyanation with nucleophilic cyanating reagent, 10 we envisioned that reductive cyanation with two electrophilic partners and opposite reaction mode might offer an efficient and convenient solution to construct C−CN bond, which would not only eliminate the usage of poisonous cyanide and vulnerable organometallic reagents but also exhibit both impressive robustness and remarkable flexibility.…”

“…On the other side, the development on preparing methods of other α-cyano carbonyls manifests sharp contrast to the diverse strategies to obtain α-cyano ketones. As we know, only one elegant pathway to α-cyano carboxamides via copper-catalyzed cyanation of tertiary bromides with zinc cyanide was reported by Nishikata and Kuninobu recently . Therefore, the reaction protocol, which can be simultaneously applicable for the synthesis of α-cyano ketones, esters, and carboxamides bearing a quaternary center, has yet to be established.…”

α-Amino Radical-Mediated Diverse Difunctionalization of Alkenes: Construction of C–C, C–N, and C–S Bonds

“…Though TMSY reagents (Y = CN, N 3 , or NCS), especially TMSCN, have been used to trap the radical intermediate genarated from the addition of •CF 3 or a nitrogen radical to CC bonds, methodologies in which two Y functionalities are introduced have been rare, and a general methodology for 1,2-R F /Y difunctionalization with three Y functional groups has not been reported. Inspired by these reports and our previous work, we sought a broad catalytic methodology for 1,2-difunctionalization and focused on the formation of C–C, C–N, C–S bonds, instead of the C–O bond of a mixed peroxide to provide a greater diversity of compounds.…”