Homocoupling of 1-Alkynyl Tosylamides

Abstract

N,N′-substituted-buta-1,3-diyne-1,4-tosylamides have been synthesized for the first time, in good to excellent yields, via copper-catalyzed dimerization of the corresponding 1-alkynyltosylamides.

alkyne homocoupling - butadiynes - copper-catalyzed dimerization - ynamides

References

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1b See also: Mulder JA. Kurtz KCM. Hsung RP. Synlett  2003,  1379 

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As well as finding no precedent for the Glaser reaction of ynamides, we found only few ynamines dimerization:

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10 For a recent review on acetylenic coupling, see: Siemsen P. Livingston RC. Diederich F. Angew. Chem. Int. Ed.  2000,  39:  2632 

11

Trimethylsilyl derivatives are interesting substrates that can also be prepared in a single step from the corresponding N-alkyltosylamides by reaction with hypervalent iodonium reagents, see: ref. [5b]

12 Liu Q. Burton DJ. Tetrahedron Lett.  1997,  38:  4371 

13

The dimerization of 2a performed without the co-catalyst CuI gave slow decomposition of starting material and performed only with CuI and Et₃N gave a slow dimerization process.

14 Hay AS. J. Org. Chem.  1962,  27:  3320 

15

Typical Procedure for the Homocoupling of 1-Alkynyl Tosyl Amides: TMEDA (5 µL, 0.033 mmol) was added to a suspension of CuI (3 mg, 0.017 mmol) in dry acetone (4 mL) under O₂ atmosphere, at r.t. After 15 min, a solution of 2a (45 mg, 0.177 mmol) in acetone (4 mL) was added and the mixture was vigorously stirred until TLC showed complete comsuption of the starting material (3 h). After removal of the solvent, the crude residue was purified by column chromatography on silica gel using a mixture of hexanes/EtOAc 1:3 as eluent, yielding 41 mg (91%) of 3a as white prisms, mp 157-159 °C (dec.). ¹H NMR (250 MHz, CD₃Cl): δ = 7.62-7.56 (m, 4 H, ArH), 7.36-7.26 (m, 10 H, ArH), 7.25-7.17 (m, 4 H, ArH), 2.44 (s, 6 H, 2 × CH₃). ¹³C NMR + DEPT (62.83 MHz, CD₃Cl): δ = 145.3 (2 × C), 138.2 (2 × C), 133.1 (2 × C), 129.7 (4 × CH), 129.2 (4 × CH), 128.7
(2 × CH), 128.1 (4 × CH), 126.4 (4 × CH), 75.7 (2 × C), 58.5 (2 × C), 21.7 (2 × CH₃). MS: m/z (%) = 545 (29) [M⁺ - CH₃], 369 (57), 322 (55), 278 (97), 247 (63), 218 (82), 139 (100), 91 (60). Anal. Calcd (%) for C₃₀H₂₄N₂O₄S₂: C, 66.65; H, 4.47; N, 5.18; S, 11.86. Found: C, 66.21; H, 4.21; N, 5.27; S, 11.67.

16

Although N,N′-phenyl-buta-1,3-diyne-1,4-tosylamide(3a) decomposed during work-up under acidic conditions followed by removal of the solvent in a rotavapor, a pure sample of 3a was unaffected when dissolved in EtOAc or CHCl₃ before mixing with HCl (5%) or NaOH (10%).

17 Valenti E. Pericàs MA. Serratosa F. J. Am. Chem. Soc.  1990,  112:  7405 

Ynamide 2b reacted much faster (in 0.5 h) than the non-nitrogenated acetylenes used by Mori and coworkers, which took 6-12 h. See:

18a Ikegashira K. Nishihara Y. Hirabayashi K. Mori A. Hiyama T. Chem. Commun.  1997,  1039 

18b Nishihara Y. Ikegashira K. Hirabayashi K. Ando J.-I. Mori A. Hiyama T. J. Org. Chem.  2000,  65:  1780 

19 Greene TW. Wuts PGM. Protective Groups in Organic Synthesis   2nd ed.:  John Wiley and Sons; New York: 1991.