Mendeleev Communications Electronic Version, Issue 3, 1997 (pp. 87–126) An effective synthesis of 4-alkynyl-substituted sydnones Il’ya A. Cherepanov, Diana D. Bronova, Elena Yu. Balantseva and Valery N. Kalinin* A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 117813 Moscow, Russian Federation. Fax: +7 095 135 5085 3-Phenyl-4-trimethylsilylethynylsydnone has been obtained for the first time, and a preparative method for the exchange of a Me3Si group by an organic substrate from organohalides in the presence of Pd0/CuI, Et3N and Bun 4NF·3H2O is proposed.Mesoionic heterocycles, especially sydnones and sydnone imines, are of considerable interest as potentially physiologically-active compounds.1 The additional introduction of carbo- and/or heterocyclic substituents into sydnones can have a great impact on their biological activity.Previously we have found that 4-cuprio-3-phenylsydnone reacts with organohalides in the presence of Pd0 to give cross-coupling products including 4-alkynyl-substituted sydnones.2,3 In this work we tried to obtain 4-ethynyl-3-phenylsydnone 1, because this compound is usable as a base for the synthesis of different 4-carbo- and 4-heterocyclic derivatives of sydnones by cycloaddition [3+2] and [4+2] reactions.4,5 However, our attempts to synthesize 1 from reactions of 1-bromoacetylene with 4-cuprio-3-phenylsydnone under Pd0 or PdII catalysis conditions have not been successful.This may be due to the rather high acidity of the CH bond in terminal acetylenes.In this respect, to obtain 1 we have used 1-bromo- 2-trimethylsilylacetylene6 as the acetylenic compound for the cross-coupling reaction, because it is known that the silicon–carbon bond in acetylenes is easily cleaved by fluorine anion.7 Table 1 Palladium-catalysed cross-coupling reaction of 4-ethynyl-3-phenylsydnone (1, in situ) with organohalides. Reagents and conditions: i, Bun 4NF·3H2O, THF, 20 °C; ii, 5% Pd(PPh3)4/5% CuI, 4 equiv.Et3N, THF, 20 °C, 2–24 h. RHal Reaction time/h Product Mp/°C Yield (%) 1 3 133–135 (Lit. data 135.5–137)3 85 2 2 159–161 97 3 5 150–152 67 4 24 0 5 5 141–143 49 6 Br–CH=CH–Ph 22 112.5–114 40 7 24 123–125 26 8 24 0 9 3 148–150 47 N N O O Ph CºCSiMe3 N N O O Ph CºCH N N O O Ph CºCR i RHal, ii + – – + – + I N N O O Ph CºC + – I NO2 N N O O Ph CºC NO2 + – I CO2Me N N O O Ph CO2Me CºC + – Br CO2Me I N= CH Cl N N O O Ph Cl N=CH CºC + – = N N O O Ph CºC CH=CH Ph + – = –Ph N I N N O O Ph CºC N + – N Br O Br O Me N N O O Ph CºC O O Me + – =Mendeleev Communications Electronic Version, Issue 3, 1997 (pp. 87–126) It has been found that the interaction of 4-cuprio- 3-phenylsydnone with 1-bromo-2-trimethylsilylacetylene under Pd0 catalysis readily results in the formation of the desired 3-phenyl-4-trimethylsilylethynylsydnone – (5-oxido-3-phenyl- 4-trimethylsilylethynyl-1,2,3-oxadiazol-3-ium) 2.† Treatment of 2 with Bun 4NF·3H2O in THF at 0 °C promotes rapid cleavage of the C–SiMe3 bond and the formation of 1 (HPLC data), but all our attemps to prepare 1 in pure form failed due to its instability.Terminal acetylenes react with organohalides under Pd0/CuI catalysis and in the presence of bases to afford crosscoupling products.8,9 Compound 1 formed in situ from 2 under the action of Bun 4NF·3H2O also readily engages in this crosscoupling reaction with vinyl-, aryl- and heteroaryl-halides to give 1-substituted-2-(3-phenylsydnon-4-yl)acetylenes. The main results are presented in Table 1.‡ From Table 1, the palladium-catalysed cross-coupling reaction of 1 with iodoaryls occurs rather fast and in good yields (runs 1–3,5) whereas bromoaryls (runs 4,8) hardly react at all. Bromovinyl (run 6), 2-iodopyrydine (run 7) and 4-bromo-6-methyl-2H-pyran-2-one (run 9) form cross-coupling products in moderate yield.In conclusion, the cross-coupling reactions proposed here are useful as preparative methods for obtaining disubstituted acetylenes where one substituent is a sydnonyl radical. The authors are very grateful to Dr.O. S. Shilova for the sample of 4-bromo-6-methyl-2H-pyran-2-one. References 1 M. Ohta and H. Kato, Non-Benzenoid Aromatics, ed. J. P. Snyder, Academic Press, New York, 1969, p. 117. 2 V. N. Kalinin and Fan Min She, J.Organomet. Chem., 1988, 352, C34. 3 V. N. Kalinin, D. N. Pashchenko and Fan Min She, Mendeleev Commun., 1992, 60. † 5-Oxido-3-phenyl-4-trimethylsilylethynyl-1,2,3-oxadiazo-3-ium 2: mp 74.5–76.5 °C. Found (%): C 60.45, H 5.46, N 10.38. Calc. (%) for C13H14N2O2Si: C 60.44, H 5.46, N 10.48. 1H NMR (d, ppm, CDCl3): 0.20 (s, 9H, SiMe3), 7.50–7.70 (m, 3H) and 7.75–7.80 (m, 2H, Ph).IR (n/cm–1, CHCl3): 1764 (CO), 1252 and 848 (SiMe3). ‡ Typical procedure: A solution of Bun 4NF·3H2O (1 mmol) in 15 ml of THF was added dropwise to a stirred mixture of 3-phenyl-4-trimethylsilylethynylsydnone (1 mmol), organohalide (3 mmol), CuI (0.05 mmol), Pd(PPh3)4 (0.05 mmol) and Et3N (4 mmol) in 20 ml of THF. The mixture was stirred 2–24 h (see Table 1) at 20 °C. The solvent was evaporated in vacuo, and the product purified by chromatography on silica (eluent CHCl3) and recrystallisation from CHCl3–hexane (3 : 1).All compounds synthesized gave satisfactory analytical and spectroscopic data. 4 A. S. Onishenko, Dienovyi Sintez (The synthesis of dienes), Izd. Akad. Nauk SSSR, Moscow, 1963 (in Russian). 5 1,3-Dipolar Cycloaddition Chemistry, ed. A. Padwa, Wiley–Interscience, New York, 1984. 6 J. Miller, Synthesis, 1983, 128. 7 W. P. Weber, Silicon Reagents for Organic Synthesis, Springer–Verlag, New York, 1983. 8 V. N. Kalinin, Synthesis, 1992, 413. 9 R. Rossi, A. Carpita and F. Belina, Organic Preparation and Procedures Int., 1995, 27, 127. N N O Ph Cu O N N O Ph CºCH O i + BrCºCH + – – + Scheme 1 Reagents and conditions: i, Pd(PPh3)4, THF, 20–60 °C. 1 N N O Ph Cu O N N O Ph CºCSiMe3 O + BrCºCSiMe3 N N O Ph CºCH O ii i 2 1 Scheme 2 Reagents and conditions: i, 5% Pd(PPh3)4, THF, 20 °C; ii, Bun 4NF·3H2O. + – – + + – Received: Moscow, 3rd September 1996 Cambridge, 18th January 1997; Com. 6/06074I