Pathways in the Degradation of Geminal Diazides Kristina Holzschneider, † Andreas P. Ha ̈ ring, † Alexander Haack, ‡ Daniel J. Corey, § Thorsten Benter, ‡ and Stefan F. Kirsch* ,† † Organic Chemistry and ‡ Physical and Theoretical Chemistry, Bergische Universitä t Wuppertal, Gaußstr. 20, 42119 Wuppertal, Germany § Department of Chemistry, University of Michigan-Flint, 303 E. Kearsley St., Flint, Michigan 48502, United States *S Supporting Information ABSTRACT: The degradation of geminal diazides is described. We show that diazido acetates are converted into tetrazoles through the treatment with bases. The reaction of dichloro ketones with azide anions provides acyl azides, through in situ formation of diazido ketones. We present experimental and theoretical evidence that both fragmentations may involve the generation of acyl cyanide intermediates. The controlled degradation of terminal alkynes into amides (by loss of one carbon) or ureas (by loss of two carbons) is also shown. G eminal diazides are a largely disregarded class of compounds. 1 Despite an inspiring report by Forster and co-workers as early as in 1908, 2 only a small number of further reports described the synthesis of geminal diazides, 3 and even less studies focused on their reactivities. 4,5 We recently launched a research program that aims to unveil new reactions with geminal diazides, 6 and we also started to reinvestigate previously reported reactions in a systematic way. 7 In the course of this program, it became apparent that geminal diazides derived from 1,3-dicarbonyls are powerful acylating agents that allow for the acylation of primary amines (Scheme 1). 8 Since we unequivocally observed the stoichiometric evolution of tert-butyl 2,2-diazidoacetate (4) using 1 H NMR spectroscopy when diazido acylacetate 1 reacted with primary amine 2 to give amide 3, this acyl transfer reaction was believed to be a classical substitution: The attack of the substituting amine at the carbonyl carbon is followed by elimination of the diazido acetate leaving group 4. In the presence of base additives, however, it was found that the diazido acetate 4 was rapidly converted, and azide functionalities have vanished completely after, for example, basic workup conditions. 8a When studying the related acylation of amine 2 with diazido compounds derived from 1,3-diketones (e.g., 5), the proposed diazido leaving group 6 was never detected; instead, a second acyl transfer onto the amine was observed leading to the overall formation of both amides 3 and 7. 8b Since little is known about the possible degradation pathways of geminal diazides, 4a-g we then began to carefully investigate the fate of the two diazido species A and B. These diazido compounds are potentially hazardous, 9 and gaining knowledge on their reactivity and in particular on their controlled degradation is important when new methods with diazido intermediates are envisioned. The results presented in this work show how the reactive diazido compounds can be used to create challenging structural entities, such as tetrazoles and acyl azides, through novel pathways. Finally, we demonstrate that the diazide degradation can be applied to the question of how to manipulate terminal alkynes, and a novel sequence is presented that results in the controlled dismounting of the alkyne through scission of either a one- carbon or a two-carbon unit. Our studies began again with diazido ester 4, derived from the conversion of diazido acylacetate 1 with benzylamine (Scheme 2). The diazido ester 4 was readily isolated by submitting the crude reaction mixture directly onto silica for purification through flash chromatography (in up to 70% yield). The single other compound, besides the amide main product 3, was the carbamate 8, a compound that was formed in surprisingly inconsistent yields nevertheless, it was possible to isolate the carbamate 8 in up to 20% yield when a 2-fold excess of benzylamine was employed (see Scheme 2a). Since the Received: April 27, 2017 Scheme 1. Diazido-Containing Compounds in the Acylation of Amines Note pubs.acs.org/joc © XXXX American Chemical Society A DOI: 10.1021/acs.joc.7b01019 J. Org. Chem. XXXX, XXX, XXX-XXX