Benzylation of Nitroalkanes Using Copper-Catalyzed Thermal Redox Catalysis: Toward the Facile C-Alkylation of Nitroalkanes

Abstract

The C-alkylation of nitroalkanes under mild conditions has been a significant challenge in organic synthesis for more than a century. Herein, we report a simple Cu(I) catalyst, generated in situ, that is highly effective for C-benzylation of nitroalkanes using abundant benzyl bromides and related heteroaromatic compounds. This process, which we believe proceeds via a thermal redox mechanism, allows access to a variety of complex nitroalkanes under mild reaction conditions and represents the first step towards developing a general catalytic system for the alkylation of nitroalkanes.

Metal-Free C-Arylation of Nitro Compounds with Diaryliodonium Salts

“…25c Scheme 6 depicts product formation via two different T-shaped intermediates that could be in fast equilibrium, with product formation to 3 either by normal ligand coupling (A) or via a [2,3]-rearrangement (B).…”

“…[2][3] While α-arylation of carbonyl compounds has been studied extensively, 4 the arylation of nitroalkanes remains largely unexplored. Stoichiometric use of heavy metal reagents based on lead 5 or thallium 6 generates toxic waste, while reactions with triphenylbismuth reagents 7 have poor atom efficiency.…”

General Route for Preparing β-Nitrocarbonyl Compounds Using Copper Thermal Redox Catalysis

“…15,16 We believe this reaction proceeds via a benzyl-stabilized radical, 16 which suggests that other alkyl bromides bearing radical-stabilizing groups might be viable coupling partners for the reaction.…”

Facile Synthesis of Single α‐tert‐Alkylated Acetaldehydes by Hydroxyalkylation of Enamides in Aqueous Solution

“…Among them, single a-tert-alkylated acetaldehydes, which have a1 ,4dicarbonyl skeleton, are extremelyu seful synthetic intermediates for the synthesis of bioactive compounds, such as (À)-jiadifenolide, [1] LY426965, [2] and (À)-mesembrine [3] (Figure 1). [9] Similart ot he alkylations of enols [10] or nitroalkanes, [11] alkylations of enamides to produce a-tert-alkylateda ldehydes is challenging due to the limitedk nownp rotocols for tert-alkylations. Generally,d irect alkylation of acetal-dehyde with an alkyl halide under basic conditions is very difficult due to ar apid formationof aldol adducts.…”