Efficient Synthesis of N-Sulfonylacetamidines from Propiolic Acid by Copper-Catalyzed Three-Component Coupling Reactions

Abstract

Using propiolic acid as one of the reacting components, a copper-catalyzed three-component reaction of sulfonyl azide and amines affords N-sulfonylacetamidines via a decarboxylation process in high yields under mild conditions. This one-pot method is efficient, general, and versatile.

Key words

amidine - azides - copper - catalysis - propiolic acid

References and Notes

• 1 Greenhill JV. Lue P. Prog. Med. Chem.  1993,  30:  203 
• 2a Nötzel MW. Rauch K. Labahn T. de Meijere A. Org. Lett.  2002,  4:  839 
• 2b Szczepankiewicz BG. Rohde JJ. Kurukulasuriya R. Org. Lett.  2005,  7:  1833 
• 3a Boyd GV. In The Chemistry of Amidines and Imidates   Vol. 2:  Patai S. Rappoport Z. Wiley; New York: 1991. 
• 3b Sienkiewich P. Bielawski K. Bielawska A. Palka J. Environ. Toxicol. Pharmacol.  2005,  20:  118 
• 3c Barker J. Kilner M. Coord. Chem. Rev.  1994,  133:  219 
• 3d Lee MY. Kim MH. Kim J. Kim SH. Kim BT. Jeong IH. Chang S. Kim SH. Chang SY. Bioorg. Med. Chem. Lett.  2010,  20:  541 
• 4a Dömling A. Chem. Rev.  2006,  106:  17 
• 4b Zhu J. Bienaymé H. Multicomponent Reactions   Wiley-VCH; Weinheim: 2005. 
• 4c Ramón DJ. Yus M. Angew. Chem. Int. Ed.  2005,  44:  1602 
• 4d Dömling A. Ugi I. Angew. Chem. Int. Ed.  2000,  39:  3168 
• 5a Chen L. Li CJ. Adv. Synth. Catal.  2006,  348:  1459 
• 5b Montgomery J. Angew. Chem. Int. Ed.  2004,  30:  3890 
• 5c Zhang Y. De Korver KA. Lohse AG. Zhang YS. Huang J. Hsung RP. Org. Lett.  2009,  11:  899 
• 6a Yoo EJ. Chang S. Curr. Org. Chem.  2009,  13:  1766 
• 6b Lu P. Wang Y. Synlett  2010,  165 
• 7 Kim SH. Jung DY. Chang S. J. Org. Chem.  2007,  72:  9769 
• 8 Bae I. Han H. Chang S. J. Am. Chem. Soc.  2005,  127:  2038 
• 9a Cho SH. Yoo EJ. Bae I. Chang S. J. Am. Chem. Soc.  2005,  127:  16046 
• 9b Cho SH. Chang S. Angew. Chem. Int. Ed.  2007,  46:  1897 
• 10a Yoo EJ. Bae I. Cho SH. Han H. Chang S. Org. Lett.  2006,  8:  1347 
• 10b Zhang W. Kuang C. Yang Q. Chin. J. Chem.  2009,  27:  1727 
• 11 Cho SH. Chang S. Angew. Chem. Int. Ed.  2008,  47:  2836 
• 12 Cui SL. Wang J. Wang YG. Org. Lett.  2008,  10:  1267 
• 13 Kim J. Lee SY. Lee J. Do Y. Chang S. J. Org. Chem.  2008,  73:  9454 
• 14a Chang S. Lee M. Jung DY. Yoo EJ. Cho SH. Han SK. J. Am. Chem. Soc.  2006,  128:  12366 
• 14b Kim JY. Kim SH. Chang S. Tetrahedron Lett.  2008,  49:  1745 
• 14c Yoo EJ. Chang S. Org. Lett.  2008,  10:  1163 
• 14d Mandal S. Gauniyal HM. Pramanik K. Mukhopadhyay B. J. Org. Chem.  2007,  72:  9753 
• 14e Xu X. Cheng D. Li J. Guo H. Yan J. Org. Lett.  2007,  9:  1585 
• 14f Whiting M. Fokin VV. Angew. Chem. Int. Ed.  2006,  45:  3157 
• 15a Cui SL. Lin XF. Wang YG. Org. Lett.  2006,  8:  4517 
• 15b Cui SL. Wang J. Wang YG. Org. Lett.  2007,  9:  5023 
• 15c Cui SL. Wang J. Wang YG. Tetrahedron  2008,  64:  487 
• 15d Lu W. Song W. Hong D. Lu P. Wang Y. Adv. Synth. Catal.  2009,  351:  1768 
• 17 Yoo EJ. Ahlquist M. Bae I. Sharpless KB. Fokin VV. Chang S. J. Org. Chem.  2008,  73:  5520 

16

General Procedure for the Synthesis of 3
A solution of sulfonyl azide (1.2 mmol), amine (1.2 mmol), propiolic acid (1.0 mmol), DBU (1.5 mmol), and CuI (0.1 mmol) in THF (2 mL) was stirred at r.t. under N₂ for 10 h. After the reaction was completed, which was monitored with TLC, the reaction solution was diluted with CH₂Cl₂ (2 mL) and then with aq NH₄Cl solution (3 mL). The mixture was stirred for an additional 30 min at r.t., and the two layers were separated. The aqueous layer was extracted with CH₂Cl₂ (3 × 3 mL), and the combined organic layers were dried over Na₂SO₄ and concentrated in vacuo. The crude residue was purified by flash column chromatography with EtOAc-PE to give N-sulfonylacetamidines 3a-l.
Selected Data
N -Ethyl- N -phenyl- N ′-tosylacetamidine (3a) Light yellow solid, mp 130.0-131.0 ˚C. IR (KBr): 3458, 2929, 1547, 1495, 1267, 1139, 1089, 685 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): d = 7.88 (2 H, d, J = 8.2 Hz), 7.45 (2 H, t, J = 7.8 Hz), 7.39 (1 H, t, J = 7.5 Hz), 7.29 (2 H, d, J = 8.0 Hz), 7.12 (2 H, d, J = 7.5 Hz), 3.83 (2 H, q, J = 14.2 Hz,), 2.42 (3 H, s), 2.24 (3 H, s), 1.12 (3 H, t, J = 7.1 Hz). ^¹³C NMR (125 MHz, CDCl₃): d = 165.4, 141.9, 141.6, 140.3, 130.0, 129.1, 128.6, 127.7, 126.3, 47.2, 21.4, 19.8, 11.9. ESI-MS: m/z (%) = 316 [M⁺]. HRMS: m/z calcd for C₁₇H₂₁N₂O₂S: 317.1324 [M + H]⁺; found: 317.1321.
N - p -Tolyl- N ′-tosylacetamidine (3k) Light yellow solid (a mixture of two isomers with a ratio 1:3, which is tentatively assigned as Z/E of the generated imino C=N double bond), mp 109.6-127.9 ˚C. IR (KBr): 3750, 3308, 1535, 1457, 1275, 1143, 1089, 730 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 9.7 (0.7 H, br, Z/E), 7.87 (1.9 H, d, J = 8.2 Hz, E), 7.82 (0.6 H, d, J = 8.0 Hz, Z), 7.36 (0.6 H, d, J = 8.5 Hz, Z), 7.31 (2 H, d, J = 8.1 Hz, E), 7.26 (0.6 H, d, J = 8.0 Hz, Z), 7.20 (2 H,d, J = 8.0 Hz, E), 7.08 (0.6 H, d, J = 8.5 Hz, Z), 7.02 (2 H, d, J = 8.2 Hz, E), 2.61 (0.9 H, s, Z), 2.43 (3 H, s, E), 2.41 (1.0 H, s, Z), 2.37 (3 H, s, E), 2.30 (1.0 H, s, Z), 2.01 (2.9 H, s, E). ^¹³C NMR (125 MHz, CDCl₃): δ = 165.6, 162.9, 143.0, 142.2, 140.4, 139.3, 138.2, 135.2, 134.8, 134.0, 130.2, 129.4, 129.3, 129.2, 126.4, 126.3, 126.1, 121.7, 22.0, 21.7, 21.5, 21.4, 20.9, 20.8. ESI-MS: m/z (%) = 302 [M⁺]. HRMS: m/z calcd for C₁₆H₁₉N₂O₂S: 303.1167 [M + H]⁺; found: 303.1170.