A Practical Synthesis of Valuable Strained Eight‐Membered‐Ring Derivatives for Click Chemistry

A convenient and cost‐effective synthetic access to cyclooctyne and trans‐cyclooctene derivatives is described. A cyclopropanation step using copper powder in place of Rh2(OAc)4 as catalyst and a symmetric diazomalonate resulted in a drastic decrease in the overall cost of the synthesis. Further derivatizations allowed us to characterize, for the first time, the structure of a BCN analogue by X‐ray crystallography, and to obtain a library of derivatives that could potentially be useful for applications in metal‐free click chemistry. A convenient and cost‐effective synthetic access to cyclooctyne and trans‐cyclooctene derivatives is described. A cyclopropanation step using copper powder in place of Rh2(OAc)4 as catalyst and a symmetric diazomalonate resulted in a drastic decrease in the overall cost of the synthesis.