Synthesis of pyrazoles through catalyst-free cycloaddition of diazo compounds to alkynes

Diazo compounds as highly tunable reactants in 1,3-dipolar cycloaddition reactions with cycloalkynes

“…37 1,3-Dipolar cycloaddition reactions of diazo compounds with polarized alkenes and alkynes are well known. 38–40 Still, chemical biologists have not employed this strategy, presumably because polarized alkenes and alkynes lack chemoselectivity in a biological context and because known cycloaddition reactions of diazo compounds involve either highly reactive diazoalkanes generated in situ , 41,42 or highly stabilized diazo compounds 43 requiring elevated reaction temperatures 44 or toxic metal catalysts to attain useful reaction rates. 45–50 Now that a wide variety of diazo compounds are readily accessible from azides in a single step, we sought to assess their reactivity in strain-promoted cycloaddition reactions with forefront cycloalkynes.…”

Regioselective One‐Step Synthesis of Pyrazoles from Alkynes and N‐Tosylhydrazones: [3+2] Dipolar Cycloaddition/[1,5] Sigmatropic Rearrangement Cascade

“…[13] Moreover, the [3+2] cycloaddition/ [1,5] sigmatropic rearrangement sequence has been previously described in reactions of a-diazocarbonyl compounds with alkynes, [14] but the examples with nonstabilized diazo compounds are very limited in scope and synthetic interest. [24] Furthermore, the reactions of tosylhydrazones with terminal alkynes in the presence of a Cu I catalyst proceed in a completely different manner, thus giving rise to allenes by formation of a Cu carbene intermediate.…”

“…[10] For these reasons, the development of new methodologies for the regioselective synthesis of polysubstituted pyrazoles continues to be an active area of research of high impact in fine chemistry. [11] The most popular approaches to the synthesis of trisubstituted pyrazoles consist of: 1) condensation of hydrazines with 1,3-dicarbonyl compounds or synthetic equivalents; [12] 2) [3+2] cycloadditions of diazo compounds or other N = Ncontaining dipoles with alkynes [13][14][15] or alkenes; [16] 3) transition-metal-catalyzed cross-coupling reactions. [17] Nevertheless, the efficient preparation of 3,4,5-trisubstituted pyrazoles in a regioselective manner is still a challenging task which involves several synthetic steps.…”

[3+2] Cycloadditions of N-Protected ‘(S)-Diazoproline’ with Selected Acetylenes

“…The characteristic absorption of HC(4) of the pyrazole ring appeared at 110.0 ppm, in good agreement with the data reported for diethyl 1H-pyrazole-3,5-dicarboxylate. 6 In contrast to 5a, the 1 H-NMR spectrum in CDCl 3 at room temperature evidenced the presence of two rotamers of the product in a 91:9 ratio. Similarly, the sole product obtained from the reaction of 1b with 4b was identified as a 53:47 mixture of two rotamers of the analogous regioisomer 5e.…”

“…6 However, cyclic α-diazo ketones react with acetylenes to yield fused polycyclic pyrazole derivatives via ring enlargement of the initially formed spirocyclic 3H-pyrazol. 6 Syntheses of phosphonylated pyrazoles and related phosphorus-containing heterocycles have been reviewed recently. 7 Only one report on the [3+2] cycloaddition of an acetylene phosphonate with diazomethane is known leading to a 3-phosphonylated pyrazole in low yield.…”