Efficient Synthesis of Isoquinolines via Rh(III)-Catalyzed Oxidative Annu­lation of Picolinamides with Alkynes

Abstract

An efficient synthesis of isoquinolines via Rh(III)-catalyzed oxidative annulation of picolinamides with alkynes using Cu(OAc)₂ as an oxidant has been developed. The scope of the reaction was studied with a selection of various picolinamides and alkynes, and the desired isoquinolines were obtained in good to excellent yields.

Key words

isoquinoline - rhodium(III) - C–H activation - pyridine - oxidative annulation

• References and Notes

• 1 Bentley KW. In The Isoquinoline Alkaloids . Vol. 1. Hardwood Academic; Amsterdam: 1998
• 2 Organic Reactions . Vol. 6. Adams R. Wiley; New York: 1951: 74-206
• 3a Roesch KR, Larock RC. J. Org. Chem. 1998; 63: 5306
• 3b Roesch KR, Larock RC. Org. Lett. 1999; 1: 553
• 4 Korivi RP, Cheng C.-H. Org. Lett. 2005; 7: 5179
• 5a Huang Q, Larock RC. Tetrahedron Lett. 2002; 43: 3557
• 5b Huang Q, Hunter JA, Larock RC. J. Org. Chem. 2002; 67: 3437
• 5c Su S, Porco JA. Jr. J. Am. Chem. Soc. 2007; 129: 7744
• 5d Niu YN, Yan ZY, Gao GL, Wang HL, Shu XZ, Ji KG, Liang YM. J. Org. Chem. 2009; 74: 2893

For selected reviews on Rh(III)-catalyzed C–H functionalization, see:
• 6a Satoh T, Miura M. Chem. Eur. J. 2010; 16: 11212
• 6b Colby DA, Tsai AS, Bergman RG, Ellman JA. Acc. Chem. Res. 2012; 45: 814
• 6c Song G, Wang F, Li X. Chem. Soc. Rev. 2012; 41: 3651
• 6d Patureau FW, Wencel-Delord J, Glorius F. Aldrichimica Acta 2012; 45: 31
• 6e Colby DA, Bergman RG, Ellman JA. Chem. Rev. 2010; 110: 624

For selected examples of Rh(III)-catalyzed coupling between arenes and alkynes, see:
• 7a Umeda N, Tsurugi H, Satoh T, Miura M. Angew. Chem. Int. Ed. 2008; 47: 4019
• 7b Yamashita M, Horiguchi H, Hirano K, Satoh T, Miura M. J. Org. Chem. 2009; 74: 7481
• 7c Guimond N, Fagnou K. J. Am. Chem. Soc. 2009; 131: 12050
• 7d Stuart DR, Alsabeh P, Kuhn M, Fagnou K. J. Am. Chem. Soc. 2010; 132: 18326
• 7e Hyster TK, Rovis T. J. Am. Chem. Soc. 2010; 132: 10565
• 7f Rakshit S, Patureau FW, Glorius F. J. Am. Chem. Soc. 2010; 132: 9585
• 7g Patureau FW, Besset T, Kuhl N, Glorius F. J. Am. Chem. Soc. 2011; 133: 2154
• 7h Muralirajan K, Parthasarathy K, Cheng C.-H. Angew. Chem. Int. Ed. 2011; 50: 4169
• 7i Song G, Chen D, Pan C.-L, Crabtree RH, Li X. J. Org. Chem. 2010; 75: 7487
• 7j Chen J, Song G, Pan C.-L, Li X. Org. Lett. 2010; 12: 5426
• 7k Chuang S.-C, Gandeepan P, Cheng C.-H. Org. Lett. 2013; 15: 5750
• 7l Shi Z, Tang C, Jiao N. Adv. Synth. Catal. 2012; 354: 2695
• 7m Zhang G, Yang L, Wang Y, Xie Y, Huang H. J. Am. Chem. Soc. 2013; 135: 8850

For selected examples, see:
• 8a Ueura K, Satoh T, Miura M. Org. Lett. 2007; 9: 1407
• 8b Patureau FW, Glorius F. J. Am. Chem. Soc. 2010; 132: 9982
• 8c Tsai AS, Brasse M, Bergman RG, Ellman JA. Org. Lett. 2011; 13: 540
• 8d Tan X, Liu B, Li X, Li B, Xu S, Song H, Wang B. J. Am. Chem. Soc. 2012; 134: 16163
• 8e Gong T.-J, Xiao B, Liu Z.-J, Wan J, Xu J, Luo D.-F, Fu Y, Liu L. Org. Lett. 2011; 13: 3235
• 8f Park SH, Kim JY, Chang S. Org. Lett. 2011; 13: 2372
• 8g Li B.-J, Wang H.-Y, Zhu Q.-L, Shi Z.-J. Angew. Chem. Int. Ed. 2012; 51: 3948
• 8h Qin X, Liu H, Qin D, Wu Q, You J, Zhao D, Guo Q, Huang X, Lan J. Chem. Sci. 2013; 4: 1964
• 8i Zhou B, Du J, Yang Y, Li Y. Org. Lett. 2013; 15: 2934
• 8j Dong J, Long Z, Song F, Wu N, Guo Q, Lan J, You J. Angew. Chem. Int. Ed. 2013; 52: 580
• 8k Shang Y, Jie X, Zhao H, Hu P, Su W. Org. Lett. 2014; 16: 416 ; and references therein
• 9a Stuart DR, Bertrand-Laperle M, Burgess KM. N, Fagnou K. J. Am. Chem. Soc. 2008; 130: 16474
• 9b Fukutani T, Umeda N, Hirano K, Satoh T, Miura M. Chem. Commun. 2009; 5141
• 9c Too PC, Wang Y.-F, Chiba S. Org. Lett. 2010; 12: 5688
• 9d Zhang X, Chen D, Zhao M, Zhao J, Jia A, Li X. Adv. Synth. Catal. 2011; 353: 719
• 9e Hyster TK, Rovis T. Chem. Commun. 2011; 47: 11846
• 9f Zheng L, Ju J, Bin Y, Hua R. J. Org. Chem. 2012; 77: 5794
• 10 Zhou J, Li B, Hu F, Shi B.-F. Org. Lett. 2013; 15: 3460
• 11a Takahashi T, Li Y, Stepnicka P, Kitamura M, Liu Y, Nakajima K, Kotora M. J. Am. Chem. Soc. 2002; 124: 576
• 11b Iwayama T, Sato Y. Chem. Commun. 2009; 5245
• 11c Fukutani T, Hirano K, Satoh T, Miura M. J. Org. Chem. 2011; 76: 2867
• 11d Song G, Gong X, Li X. J. Org. Chem. 2011; 76: 7583
• 12 General Procedure for the Synthesis of Isoquinolines 3 via Oxidative Annulation of Picolinamides 1 with 2: N,N-Diethylpicolinamide (1; 0.2 mmol, 1.0 equiv), [Cp*RhCl₂]₂ (0.005 mmol, 2.5 mol%), AgSbF₆ (0.02 mmol, 10 mol%), Cu(OAc)₂ (0.4 mmol, 2.0 equiv), alkyne 2 (0.44 mmol, 2.2 equiv) and DCE (2 mL) were added to a 20-mL Schlenk tube. After being purged with nitrogen, the mixture was stirred at 120 °C for 24 h. Then concd aq NH₃ (2 mL) was added and stirred for 5 min. The resulting mixture was extracted with EtOAc. The organic layer was dried over Na₂SO₄, concentrated under reduced pressure and purified by chromatography on silica gel to afford isoquinoline 3. 5,6,7,8-Tetraphenylisoquinoline-1-carboxylic Acid Diethylamide (3a): Compound 3a was prepared in 92% yield according to the general procedure as a white solid. ¹H NMR (400 MHz, CDCl₃): δ = 0.91 (t, J = 7.2 Hz, 3 H), 1.21 (t, J = 6.8 Hz, 3 H), 2.60–2.69 (m, 1 H), 2.72–2.81 (m, 1 H), 2.95–3.04 (m, 1 H), 3.36–3.44 (m, 1 H), 6.59 (d, J = 6.8 Hz, 1 H), 6.75–6.86 (m, 9 H), 7.04–7.13 (m, 5 H), 7.20–7.27 (m, 5 H), 7.43 (d, J = 5.6 Hz, 1 H), 8.40 (d, J = 5.6 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 168.9, 156.5, 143.3, 142.5, 141.4, 139.7, 139.6, 138.3, 138.2, 138.1, 136.5, 133.5, 131.4, 131.3, 130.9, 130.8, 130.7, 130.6 (2 × C), 127.9, 127.2 (2 × C), 127.0, 126.9, 126.7, 126.5, 125.9, 125.7, 125.6, 124.0, 120.1, 77.5, 77.2, 76.8, 45.3, 40.1, 13.8, 13.7. HRMS (EI–TOF): m/z [M⁺] calcd for C₃₈H₃₂N₂O: 532.2515; found: 532.2511.