Urea Activation of α-Nitrodiazoesters: An Organocatalytic Approach to N–H Insertion Reactions

Abstract

The combination of a urea catalyst and an α-nitro-α-diazo ester gives rise to a reactive species able to undergo insertion into the N-H bonds of anilines. This new strategy to achieve N-H insertion reactivity is in contrast to typical metal-catalyzed conditions for the generation of carbenoids from α-diazocarbonyl compounds. This report includes the extension of the insertion reaction to a three-component coupling for the construction of α-amino-α-aryl esters in high yield.

Enantioselective [4+2] Annulation to the Concise Synthesis of Chiral Dihydrocarbazoles

“…To our great delight, the desired dihydrocarbozole3a could be obtained when the chiral phosphine 4d was employed (entry 4). After surveying an array of additives, we determined that silica gel can promote elimination of HNO 2 for the aromatization process to afford the corresponding adduct in 92% yield with 94% ee (entry 4) (So and Mattson, 2012;Long et al, 2016). Other additives, such as Sc(OTf) 3 , Et 3 N, and SnCl 2 led to byproducts (for further details, see Table S1 in the Supplemental Information).…”

Modern Organic Synthesis with α-Diazocarbonyl Compounds

“…Mattson and co-workers demonstrated this idea very nicely through the use of hydrogen bonds to activate the α-nitrodiazoester 130 in the presence of the urea catalyst 131 (Scheme 165). 460,461 The ability of ureas to recognize nitro groups through intermolecular hydrogen bond interactions forms the basis of a new catalytic process, termed hydrogen bond donor (HBD) activation, which exploits the urea nitro group recognition to facilitate the loss of nitrogen gas and thereby generates a reactive intermediate capable of N−H insertion. These authors made the initial observation that α-nitro-α-diazoesters such as 130 and aniline in the presence of 20 mol % 131 in toluene yielded the α-amino-α-arylester 132.…”

Cytochrome P450-catalyzed insertion of carbenoids into N–H bonds

“…3 Carbene insertion reactions typically utilize diazo compounds, which readily generate reactive carbenoid intermediates with loss of dinitrogen in the presence of a catalyst. 4 In recent years, a variety of catalysts employing transition metal complexes, 5 ureas 6 or artificial metalloenzymes 7 have been developed. However, no enzyme or antibody has ever been reported to exhibit this mode of activation.…”