3‐Bromo N‐Alkyl Cyanamides as Versatile Building Blocks

Abstract

3‐Bromo N‐alkyl cyanamides are accessible in one simple synthetic operation from N‐alkyl azetidines reacting with cyanogen bromide. These unexplored building blocks combine two extremely useful electrophilic moieties: an alkyl bromide and a cyanamide. We demonstrate herein that they can be transformed into a range of nitrogen‐containing molecules, and especially cyclic guanidines, accessible in enantiomerically pure form. Considering the large structural diversity of available azetidines, this contribution complements the use of these strained heterocycles in diversity‐oriented synthesis.

Diastereoselective ring cleavage of azetidines with cyanogen bromide

“…The 3-bromo-N-cyanamides produced are versatile bis-electrophilic building blocks that were used for the preparation of cyclic guanidines. 11 The azetidine substrates used herein were prepared in a straightforward manner by using Gaertner's seminal reported method for the preparation of 3-hydroxy azetidines 12 adapted to different (S)-ethylamines. Treatment of epichlorohydrin with ethylamines 1-4 in water, followed by basic treatment in acetonitrile gave average-to-good yields of azetidinols 5-8 as crystalline compounds, without the need for chromatographic purification (Scheme 2).…”

Theoretical investigation of von Braun and von Braun‐like reactions

“…Moreover, the produced 3-bromocyanamides were demonstrated to be new and highly versatile biselectrophilic building blocks, notably for the preparation of guanidines. [10] In order to determine the key parameters allowing an understanding of these reactions, and especially with the aim of optimizing the level of diastereoselectivity in ring opening leading to 9, we needed to have a clear idea of its mechanism. Besides, we soon realized that despite its long history, no theoretical calculations on the von Braun reaction have been published, to the best of our knowledge.…”