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.

The Horner–Wadsworth–Emmons (HWE) reactions are vital to the chemical synthesis of complex molecules, forging a carbon–carbon double bond in the generation of α,β-unsaturated enoates from aldehydes or ketones. Despite their frequent use, the Z-stereoselective formation of α,β-unsaturated esters from aldehydes have been mostly limited to the use of the commercially available Still–Gennari reagent. Ando developed an alternative reagent to achieve the same formation with less expensive reagents. However, an α-methylated Ando-HWE reagent has remained difficult to prepare, hindering a reliable route to α,β-disubstituted Z-enoates. Here, we report the development of a preparative synthesis of a methylated Ando-HWE reagent for the highly Z-selective HWE reaction. Costing $0.49/mmol, this synthesis is significantly cheaper than the currently available Still–Gennari reagent ($11/mmol, Millipore Sigma 2018). The purification procedure does not require chromatography, with recrystallization as the only purification method, making it highly amenable to large-scale production.

safe chemical handling regarding the anomeric amide reagent employed in this study (compound 1). Many members of this class of compounds have been experimentally demonstrated to behave as mutagens in bacteria. 1 We have conducted Ames II testing of compound 1, the details of which will be reported in the supplementary information of a forthcoming publication. In the interim, we advise appropriate caution in the handling of 1: standard chemical safety protocols to minimize exposure and prevent accidental ingestion, inhalation, or dermal contact, including proper ventilation and personal protective equipment. 2 ■ REFERENCES