Alkyne Surrogates in Cycloaddition Reactions for the Preparation of Molecules of Interest

Abstract

Although alkynes are very good partners for cycloaddition reactions, their use is often associated to several drawbacks, such as multi‐steps synthesis, selectivity and stability issues or difficulty to handle for alkynes with low boiling point. In this context, alkyne surrogates have emerged as alternative substitution partners unlocking new opportunities. This review intends to highlight the outstanding power and utility of such compounds for the preparation of high value molecules.

One-Pot Synthesis of 1-Aryl-3-trifluoromethylpyrazoles Using Nitrile Imines and Mercaptoacetaldehyde As a Surrogate of Acetylene

“…Thus, nitrile imines 1 are revealed as ideal candidates for the preparation of such heterocyclic systems, e.g., through (3 + 2)cycloaddition with acetylene 16 or its surrogates. 17 Here we report the one-pot synthesis of 1-aryl-3trifluoromethylpyrazoles by using 2,5-dihydroxy-1,4-dithiane- 2,5-diol as a convenient and safe material for the surrogate of acetylene. The method comprises (3 + 3)-condensation of in situ generated nitrile imine with mercaptoacetaldehyde, followed by p-TsCl-mediated dehydration and spontaneous or thermally induced Eschenmoser sulfide contraction 18 of the first formed 4H-1,3,4-thiadiazine derivative (Scheme 2).…”

“…Nevertheless, the mentioned methods either suffer from regioselectivity issues or require harsh conditions and special equipment. Thus, nitrile imines 1 are revealed as ideal candidates for the preparation of such heterocyclic systems, e.g., through (3 + 2)-cycloaddition with acetylene or its surrogates …”

“…Thus, nitrile imines 1 are revealed as ideal candidates for the preparation of such heterocyclic systems, e.g., through (3 + 2)-cycloaddition with acetylene 16 or its surrogates. 17 …”