Copper-Catalyzed Propargylation of Nitroalkanes

Abstract

Using a commercially available, inexpensive, and abundant copper catalyst system, an efficient α-functionalization of nitroalkanes with propargyl bromides is now established. This mild and robust method is highly functional group tolerant and provides straightforward access to complex secondary and tertiary homopropargylic nitroalkanes. Moreover, the utility of these α-propargylated nitroalkanes is demonstrated through downstream functionalization to biologically relevant, five-membered N-heterocycles such as pyrroles and 2-pyrrolines.

Synthetic Approaches to the Challenging Direct C‐Alkylation and C‐Allylation of Unactivated Nitroalkanes

“…Direct propargylation of unactivated nitroalkanes using functionalized propargyl bromides 82 can be efficiently pursued under copper catalysis in the presence of a 1,2‐diamine ligand (Scheme 26). [48] To the best of our knowledge, this is the only synthetic protocol for the preparation of homopropargylic nitro derivatives 83 embedding a notable number of functional groups working on primary and secondary substituted reactants. The synthetic value of the obtained products 83 has been demonstrated by their conversion to pyrrolines 84 by preliminary nitro reduction followed by gold catalyzed cyclization.…”

Interplay of a nitro group and metal ions: from coordinative binding to noncovalent semicoordination

“…[1][2][3] Organic nitro compounds are very important building blocks for various synthetic transformations, 4 including in particular the generation of new carbon-carbon bonds in the Henry reaction, 2,4-7 nitro-Mannich reaction with amines and formaldehyde, 2 Michael reaction with multiple carboncarbon bonds, 2,4,8 and some cross-coupling processes. [9][10][11][12] In coordination chemistry, in contrast, nitro groups are less studied due to the lower nucleophilicity of the O-atom and, correspondingly, its low ability to bind metal ions. Although the capacity of the NO 2 group toward metal ligation has been sporadically reported, 13 a general overview and systematization of the coordination types have never been performed.…”

Photoredox-Nickel Dual-Catalyzed C-Alkylation of Secondary Nitroalkanes: Access to Sterically Hindered α-Tertiary Amines

“…However, nitroalkanes undergo O -alkylation under typical, uncatalyzed alkylation conditions, preventing the formation of the desired C -alkylated products. − Our group has sought to address the problem of nitroalkane C -alkylation via the development of transition metal-catalyzed nitroalkane alkylation protocols. Although we have developed copper- and nickel-catalyzed methods for C -alkylation of nitroalkanes with several classes of activated electrophiles, there are currently no methods that enable the union of a secondary nitroalkane with an unactivated alkyl halide. This transformation is required if general access to tertiary nitroalkanes is to be achieved.…”