Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 2017 Ru(II)-Catalyzed Annulation of Benzamidines and Alkynes by C-H/N-H Activation: A Facile Synthesis of 1- Aminoisoquinolines Partha Pratim Kaishap a, Gauri Duarah a, Dipak Chetia b and Sanjib Gogoi a * *Corresponding author, Tel.: +913762372948; Fax: +913762370011; Email: skgogoi1@gmail.com a Applied Organic Chemistry, Chemical Sciences & Technology Division, CSIR-North East Institute of Science and Technology, Jorhat-785006, AcSIR, India, Fax: +913762370011 Tel.: +91 3762372948; skgogoi1@gmail.com, b Department of Pharm. Sciences, Dibrugarh University, Dibrugarh Supporting Information 1
Contents Page Mechanistic Experiments 3-4 NMR spectra 5-55 2
1. Mechanistic Experiments 1.1 Intermolecular competition experiments: (a) A solution of benzamidine hydrochloride 1a (78 mg, 0.5 mmol), alkyne 2a (178 mg, 1.0 mmol), alkyne 2l (110 mg, 1.0 mmol), [RuCl 2 (p-cymene)] 2 (8 mg, 2.5 mol %), Cu(OAc) 2.H 2 O (100 mg, 0.5 mmol ) and K 2 CO 3 (65 mg, 0.5 mmol) in t AmOH (6.0 ml) was stirred in at 85 o C for 12 hours. The solvent was removed under vacuo and the crude reaction mixture was poured into water and extracted with ethylacetate (25 ml x 2). The ethylacetate layer was then washed with brine and water. Finally, it was dried over anhydrous Na 2 SO 4 and removed under vacuo. The 1 H NMR of the crude product showed the formation of 3aa and 3al in the ratio of 3.5:1. (b) A solution of benzamidine hydrochloride 1a (78 mg, 0.5 mmol), alkyne 2b (206 mg, 1.0 mmol), alkyne 2d (214 mg, 1.0 mmol), [RuCl 2 (p-cymene)] 2 (8 mg, 2.5 mol %) Cu(OAc) 2.H 2 O (100 mg, 0.5 mmol ) and K 2 CO 3 (65 mg, 0.5 mmol) in t AmOH (6.0 ml) was stirred at 85 o C for 12 hours. The solvent was removed under vacuo and the crude reaction mixture was poured into water and extracted with ethylacetate (25 ml x 2). The ethylacetate layer was then washed with brine and water. Finally, it was dried over anhydrous Na 2 SO 4 and the solvent was removed under vacuo. The 1 H NMR of the crude product showed the formation of 3ab and 3ad in the ratio of 1:1.8. (c) 3
A solution of 1b (170 mg, 1.0 mmol), 1c (174 mg, 1.0 mmol), alkyne 2a (89 mg, 0.5 mmol), [RuCl 2 (p-cymene)] 2 (8 mg, 2.5 mol %), Cu(OAc) 2.H 2 O (100 mg, 0.5 mmol) and K 2 CO 3 (65 mg, 0.5 mmol) in t AmOH (6.0 ml) was stirred at 85 o C for 12 hours. The solvent was removed under vacuo and the crude reaction mixture was poured into water and extracted with ethylacetate (25 ml x 2). The ethylacetate layer was then washed with brine and water. Finally, it was dried over anhydrous Na 2 SO 4 and the solvent was removed under vacuo. The 1 H NMR of the crude product showed the formation of 3ba and 3ca in the ratio of 1:2. 1.2 Isotopically labelled experiments A solution of benzamidine hydrochloride 1a (78 mg, 0.5 mmol), diphenylacetylene 2a (55 mg, 0.5 mmol), [RuCl 2 (p-cymene)] 2 (8 mg, 2.5 mol %), Cu(OAc) 2 (91 mg, 0.5 mmol ) and K 2 CO 3 (65 mg, 0.5 mmol) in CD 3 OD (4.0 ml) was stirred at 64 o C for 12 hours. The solvent was evaporated and the crude product obtained was purified by silica gel (100-200 mesh) column chromatography using EtOAc/Hexane (7:3) as the eluant to afford 3aa-D (60 mg, 42%). The deuterium incorporation was found to be 20% at C-8 of 3aa-D. 4
2. NMR spectra 5
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Intermolecular competition experiments: 36
Isotopically labelled experiment (Scheme 2) Structure determination of compound 3ae by spectroscopic studies 37
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Structure determination of compound 3ag by spectroscopic studies 41
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Structure determination of compound 3ag by spectroscopic studies 45
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Structure determination of compound 3aj by spectroscopic studies 50
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Structure determination of compound 3ao by NOESY Structure determination of compound 3as by spectroscopic studies 54
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