Direct Deamination of Primary Amines via Isodiazene Intermediates

Abstract

We report here a reaction that selectively deaminates primary amines and anilines under mild conditions and with remarkable functional group tolerance including a range of pharmaceutical compounds, amino acids, amino sugars, and natural products. An anomeric amide reagent is uniquely capable of facilitating the reaction through the intermediacy of an unprecedented monosubstituted isodiazene intermediate. In addition to dramatically simplifying deamination compared to existing protocols, our approach enables strategic applications of iminium and amine-directed chemistries as traceless methods. Mechanistic and computational studies support the intermedicacy of a primary isodiazene which exhibits an unexpected divergence from previously studied secondary isodiazenes, leading to cage-escaping, free radical species that engage in a chain, hydrogen-atom transfer process involving aliphatic and diazenyl radical intermediates.

Dearomatization of aromatic asmic isocyanides to complex cyclohexadienes

“…Valuable mechanistic insight was obtained from dispersion-corrected DFT calculations (for representative examples see ref. 28 ) noted as UB3LYP-D3/def2-TZVPP-SMD(THF)//UB3LYP-D3/def2-SVP-SMD(THF) that provided structural information on the role of HMTETA complexes and putative intermediates (Fig. 6 ; the Cartesian coordinates are available in the Supplementary Data file).…”

Selective Biocatalytic Defunctionalization of Raw Materials

“…Methodologies for the direct reductive deamination of amines, also called hydrodeamination, have attracted much interest in synthetic organic chemistry, from stoichiometric deamination of primary amines via isodiazene intermediates [166] to metalcatalyzed [167] and metal-free reductive deaminations of primary, secondary, and tertiary amines catalyzed by the strong boron Lewis acid tris(pentafluorophenyl) borane. [168] While numerous enzymes are used for oxidative deaminations, enzymes for catalyzing reductive deaminations are still rare.…”

Translation of a Phosphine- and Azide-Based Reaction to Chemical Modification of Biomolecules in Ionic Liquid

“…Isodiazene with ionic and neutral nitrene resonance contributors would be extremely reactive in general and are used as a reaction intermediate for versatile synthetic strategies. 30 However, there have also been reports of crystal structures of analogues of isodiazene species. Examples of crystal structures of such isodiazene derivatives include the triazene imine synthesized through an amination reaction of a cyclic triazene precursor 31 and a phosphorus analogue, as well as phosphinonitrenes formed through the azide decomposition reaction (Figure 3B).…”