Abstract:

Diazo compounds have been used extensively as precursors of metal carbene intermediates, which can subsequently undergo diverse transformations such as X–H insertion (X = C, O, S, N), and cyclopropanation. Organic azides are valuable intermediates for the synthesis of many nitrogencontaining molecules, including heterocycles and natural products. Although the isoelectronic azido and diazo functionalities are synthetically useful, the chemical behavior of compounds decorated with both azido and diazo groups remains unexplored. Some years ago, we reported the synthesis of γ-azido-α-diazo-β-keto esters and the chemoselective transformation of their multiple functional groups that ultimately gave more elaborated structures. The key azido diazo building block 1 was originally prepared in 2 steps by coupling the diazomercurial 2 with bromoacetyl bromide under anhydrous conditions followed by treating the bromo diazo intermediate 3 with azide anion (Scheme 1, Red route). Although this methodology furnished the expected product 1 in high yields and mild conditions, the diazomercurial 2 is not commercial and harmful to the health and environment. Herein, we report our initial achievements through a more simple and safe methodology for the synthesis of 1 starting from the commercially available ethyl 4-chloroacetoacetate (4) (Scheme 1, Blue route).