Copper-Catalyzed Synthesis of Pentasubstituted Pyridines from N-Sulfonyl Ketenimines, 1,1,3,3-Tetramethylguanidine, and Acetylene Dicarboxylates by Issa Yavari*, Azam Sheikhi, Manijeh Nematpour, and Zohreh Taheri Departmentof Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran (phone: þ 98-21-82883465; fax: þ 98-21-82883455; e-mail: yavarisa@modares.ac.ir) Regioselective synthesis of pentasubstituted pyridines has been developed in moderate-to-good yields by the reaction of sulfonyl azides, alkynes, and a dialkyl acetylenedicarboxylate tetramethyl- guanidine adduct catalyzed by CuI in MeCN at room temperature. Introduction. – As part of our current studies on heterocyclic synthesis [1 – 4], we report a simple and efficient procedure for the synthesis of dialkyl 5-aryl(alkyl)-4- (aryl(alkyl)sulfonamido)-6-(dimethylamino)pyridine-2,3-dicarboxylates 6 via the Cu- catalyzed tandem reaction of terminal alkynes 1, sulfonyl azides 2, 1,1,3,3-tetra- methylguanidine (TMG), and dialkyl acetylenedicarboxylates 3 ( Table). Results and Discussion. – Initially, p-toluenesulfonyl azide (2a), phenylacetylene (1a), dimethyl acetylenedicarboxylate ( 3a), and TMG were selected as the model substrates. Several catalysts such as CuI, CuBr, CuCl, and Cu powder were tested, with CuI giving the best results. Among several solvents screened, MeCN was the best. When the reaction was performed in MeCN in the presence of 1 equiv. of Et 3 N at room temperature for 8 h, it was found that product 6a was obtained in 88% yield ( Table). Thus, the optimized reaction conditions used were CuI (10 mol-%), alkyne (1 mmol), sulfonyl azide (1.2 mmol), TMG (1 mmol), and dialkyl acetylenedicarboxylate (1 mmol), in MeCN at room temperature. The structures of products 6a – 6j were assigned by IR, 1 H- and 13 C-NMR spectroscopic, and mass spectrometric data. The 1 H-NMR spectrum of 6a exhibited five singlets for Me group (d(H) 2.58), Me 2 N(d(H) 3.18), MeO (d(H) 3.79, 3.85), and NH H-atoms (d(H) 8.39), along with characteristic multiplets for the Ph H-atoms. The 13 C-NMR spectrum of 6a exhibited 19 signals in agreement with the proposed structure. The mass spectrum of 6a displayed the molecular-ion peak at m/z 483. The NMR spectra of compounds 6b – 6j are similar to those of 6a, except for the substituents, which exhibited characteristic signals in the appropriate regions of the corresponding spectra. A plausible mechanism for the formation of products 6 is outlined in the Scheme. The copper acetylide 7 , formed from 1 and CuI, undergoes a 1,3-dipolar cycloaddition with sulfonyl azide 2 to generate the triazole derivative 8 [5]. This intermediate is converted into N-sulfonyl ketenimine 4 [6], which is attacked by the CH moiety of nucleophilic adduct 5 (generated from 3 and TMG) to afford zwiterrionic species 9. Helvetica Chimica Acta – Vol. 98 (2015) 534 # 2015 Verlag Helvetica Chimica Acta AG, Zürich