Synthesis of [2‐(Trimethylsilyl)ethynyl]pyrazoles Based on Bis(trimethylsilyl)acetylene and Arylacetyl Chlorides

Abstract

A practical approach to the synthesis of [2‐(trimethylsilyl)ethynyl]pyrazoles was developed through condensation of hydrazines with enynones that are easily accessible frombis(trimethylsilyl)acetylene and arylacetyl chlorides. Optimized conditions for reactions with monoarylhydrazines permit the chemoselective formation of 5‐alkynylpyrazoles in high yields (48–94 %). When monoalkylhydrazines or the parent hydrazine is used, mixtures of 3‐ and 5‐alkynylpyrazoles are formed in 73–79 % yields. The method uses inexpensive starting materials and can be applied to a variety of substrates, which makes it convenient for the synthesis of alkynylpyrazoles.

Transition‐Metal‐Free Approach to 4‐Ethynylpyrimidines via Alkenynones

“…As compounds 4a – e possess three electrophilic centers, the formation of different heterocycles in reactions with binucleophiles may a priori be anticipated. Our previous studies showed that the triple bond in compounds 4 was not involved in reactions with hydrazines,6 and therefore we expected that the reactions between enynones 4a – e and arylamidines 7a – e (symmetrical binucleophiles) would lead to pyrimidines 8 as single products, as was indeed observed in all reactions. The triple bond remained intact, as can be seen from the pairs of signals at δ = 80–81 and 83–89 ppm, which correspond to the C≡C fragment, in the 13 C NMR spectra of all the pyrimidines.…”

“…The severe conditions required for the second step (prolonged heating at 130 °C in Ac 2 O) lead to notable tarring of the reaction mixtures and diminished yields of the desired enynones 4 in comparison with the ethoxymethylation of activated substrates such as 1,3‐dicarbonyl compounds 7. Nevertheless, we isolated compounds 4a – e in moderate yields, and in all cases the ketones 4 were formed as single stereoisomers with the ( E )‐configuration unambiguously established by X‐ray analysis for compound 4a 6…”

“…We have previously reported that the acetylenic ketones 4a , c , e are readily available from bis(trimethylsilyl)acetylene ( 1 ) and arylacetyl chlorides (Scheme ) 6. Because ketones 4a , c , e displayed high regioselectivity in their reactions with monosubstituted hydrazines,6 we decided to utilize the enynones 4 as starting materials for the synthesis of other acetylenic heterocycles. To extend the substrate scope of the reported method,6 we synthesized ketones 4b , d by the same procedure in total yields of 45 and 33 %, respectively (Scheme ).…”

“…Ketones 3a – e were prepared according to reported procedures 13. The ketones 4a , c , e were synthesized as described by us earlier,6 and this procedure was used to prepare 4b , d .…”

“…Continuing our interest in the synthesis of acetylenic heterocycles,6 we report herein a straightforward and transition‐metal‐free method for the synthesis of hitherto unknown 4‐ethynyl‐substituted pyrimidines. Our strategy includes only three synthetic steps and utilizes cheap starting materials.…”