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Synlett 2004(5): 0783-0786  
DOI: 10.1055/s-2004-817785
LETTER
© Georg Thieme Verlag Stuttgart · New York

New Alkynyl Amides by Negishi Coupling

David Rodríguez, Luis Castedo, Carlos Saá*
Departamento de Química Orgánica e Unidade Asociada ó CSIC, Facultade de Química, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
Fax: +34(981)595012; e-Mail: qocsaa@usc.es;
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Publication History

Received 9 December 2003
Publication Date:
17 February 2004 (online)

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Abstract

Negishi coupling of terminal alkynyl amides with ­(hetero)aryl iodides in the presence of Pd2dba3 and triphenyl­phosphine affords new alkynyl amides in yields of up to 90%.

Key words

alkynes - Negishi reaction - ynamides

    References

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  • 6 As far as we know, there has been a report of Sonogashira coupling of an ynamine but not of any amide. Whether or not an ynamine dimer analogous to 8 was also produced in Liao et al’s reaction is not known, because they used a solid support for their aryl iodide and washed away all components of the reaction mixture other than the cross-coupled product. See: Liao Y. Fathi R. Reitman M. Zhang Y. Yang Z. Tetrahedron Lett.  2001,  42:  1815 
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8

Typical Procedure for the Negishi Coupling of Zinc Acetylides with Aromatic Iodides: N-phenyl-N-(pyrimidin-2-ylethynyl) tosylamide (13i): n-BuLi (0.56 mL, 1.6 M in hexanes) was slowly added to a solution of 9 (0.15 g, 0.43 mmol) in dry THF (8 mL) cooled at -78 °C and the mixture was stirred for 5 min. Then, a solution of ZnBr2 (0.31 mL, 1.5 M in THF) was added via syringe and the stirring continued for 20 min at r.t. The whole mixture was transferred via cannula to a solution of Pd2dba3 (22 mg, 0.02 mmol), PPh3 (22 mg, 0.09 mmol) and 2-iodopyrimidine (0.11 g, 0.51 mmol) in dry THF (4 mL). After 3 h TLC showed complete consumption of the intermediate acetylide. The volatiles were removed and the residue was solved in EtOAc (20 mL) and washed with brine (2 × 20 mL). The organic layer was dried over anhyd Na2SO4 and evaporated to dryness. The crude residue was purified by column chromatography on silica gel using hexane/EtOAc 1:2 as eluent to yield 13i (0.12 g, 81%) as colorless prisms; mp 107-109 °C. 1H NMR (250 MHz, CDCl3): δ = 8.68-8.63 (m, 2 H, ArH), 7.75-7.67 (m, 2 H, ArH), 7.38-7.24 (m, 7 H, ArH), 7.19-7.12 (m, 1 H, ArH), 2.43 (s, 3 H, CH3). 13C NMR + DEPT (62.83 MHz, CDCl3): δ = 157.0 (2 × CH), 153.2 (C), 145.3 (C), 137.7 (C), 132.8 (C), 129.6 (2 × CH), 129.2 (2 × CH), 128.7 (CH), 128.2 (2 × CH), 126.5 (2 × CH), 119.0 (CH), 82.3 (C), 71.4 (C), 21.6 (CH3). EM: m/z (%) = 349 (2) [M+], 284 (50), 91 (37), 77 (100). Elem. anal. calcd (%) for C19H15N3O2S (349.41): C, 65.31; H, 4.33; N, 12.03; S, 9.18. Found: C, 65.62; H, 4.21; N, 11.90; S, 9.38.
N-phenyl-N-(4-nitrophenylethynyl) tosylamide (13g): pale brown needles; mp 129-131 °C. 1H NMR (250 MHz, CDCl3): δ = 8.17 (d, J = 8.7 Hz, 2 H, ArH), 7.62 (d, J = 8.2 Hz, 2 H, ArH), 7.48 (d, J = 8.7 Hz, 2 H, ArH), 7.39-7.26 (m, 7 H, ArH), 2.45 (s, 3 H, CH3). 13C NMR + DEPT (62.83 MHz, CDCl3): δ = 146.3 (C), 145.4 (C), 138.1 (C), 132.7 (C), 131.0 (2 × CH), 130.0 (C), 129.7 (2 × CH), 129.3 (2 × CH), 128.7 (CH), 128.1 (2 × CH), 126.3 (2 × CH), 123.5 (2 × CH), 89.7 (C), 69.8 (C), 21.7 (CH3); EM: m/z (%) = 392 (14) [M+], 237 (74), 91 (100).
N-(4-nitrophenylethynyl)-N-propyl tosylamide (14g): clear oil. 1H NMR (250 MHz, CDCl3): δ = 8.15 (d, J = 8.7 Hz, 2 H, ArH), 7.83 (d, J = 8.0 Hz, 2 H, ArH), 7.40 (d, J = 8.7 Hz, 2 H, ArH), 7.37 (d, J = 8.0 Hz, 2 H, ArH), 3.41 (t, J = 7.2 Hz, 2 H, CH2N), 2.46 (s, 3 H, CH3), 1.78-1.70 (m, 2 H, CH2), 0.96 (t, J = 7.4 Hz, 2 H, CH3). 13C NMR + DEPT (62.83 MHz, CDCl3): δ = 146.1 (C), 145.0 (C), 134.3 (C), 130.7 (2 × CH), 130.3 (C), 129.9 (2 × CH), 127.4 (2 × CH), 123.5 (2 × CH), 88.4 (C), 70.4 (C), 53.0 (CH2), 21.6 (CH3), 21.3 (CH2), 10.7 (CH3). EM: m/z (%): 358 (7) [M+], 150 (37), 91 (100)