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Synlett 2008(6): 924-928  
DOI: 10.1055/s-2008-1042936
LETTER
© Georg Thieme Verlag Stuttgart · New York

Silver(I)-Catalyzed Direct Route to Isoquinoline-N-Oxides

Hyun-Suk Yeoma, Sunghwan Kimb, Seunghoon Shin*a
a Department of Chemistry, Hanyang University, Seoul 133-791, Korea
Fax: +82(2)22990762; e-Mail: sshin@hanyang.ac.kr;
b Korea Basic Science Institute, 804-1 Yangcheong-Ri, Ochang-Myun, Cheongwon-Gun, Chungcheongbuk-Do 363-883, Korea
Further Information

Publication History

Received 18 December 2007
Publication Date:
11 March 2008 (online)

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Abstract

Silver trifluoromethanesulfonate efficiently catalyzes the cyclization of 2-alkynylbenzaldoxime derivatives into the corresponding isoquinoline-N-oxides. The current protocol provides a direct route to the latter skeleton under a very mild reaction condition.

Key words

AgOTf - isoquinoline-N-oxide - heterocycles - cyclo­isomerization

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One of the referees suggested the possibility of TfOH (generated by hydrolysis of metal triflates) acting as acid catalyst. When 1a was treated with 10% of TfOH in CH2Cl2, a slow decomposition was observed but none of the isoquinoline-N-oxide was observed in this case.

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Representative Preparatory Procedure for Isoquinoline N -oxide 2a (Method B) To a solution of oxime 1a (20 mg, 0.090 mmol) in CH2Cl2 (1 mL) was added AgOTf (1.2 mg, 0.0045 mmol) and the mixture was stirred at r.t. for 30 min. The solvent was removed and the residue was purified by silica gel chromatography (CH2Cl2-MeOH, 10:1) to give 17.0 mg (85%) of 2a as a white solid (method A). To a mixture of Au(IMes)Cl (5 mol%) and AgOTf (5 mol%) in CH2Cl2 (ca. 0.1 M) at r.t. was added substrate. Otherwise, a similar procedure to method B was followed.
Compound 2a: 1H NMR (400 MHz, CDCl3): δ = 8.91 (s, 1 H), 7.93-7.76 (m, 4 H), 7.76-7.67 (m, 1 H), 7.67-7.54 (m, 2 H), 7.54-7.38 (m, 3 H). 13C NMR (100 MHz, CDCl3): δ = 147.8, 137.7, 133.5, 130.4, 130.1, 129.9, 129.74, 129.70, 129.5, 128.9, 127.3, 125.5, 125.1. HRMS: m/z calcd for C30H22N2O2Na [2 M + Na]: 465.1573; found: 465.1546.
Compound 2d: 1H NMR (400 MHz, CDCl3): δ = 8.83 (s, 1 H), 8.18 (d, J = 8.2 Hz, 1 H), 7.90-7.82 (m, 2 H), 7.82-7.73 (m, 2 H), 7.71-7.60 (m, 3 H), 7.54 (d, J = 7.3 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 149.9, 145.9, 137.0, 134.2, 132.9, 131.2, 130.2, 129.8, 129.7, 128.6, 127.5, 125.5, 125.0, 124.4. HRMS: m/z calcd for C30H20N2O6Na [2 M + Na]: 555.1275; found: 555.1280.
Compound 2g: 1H NMR (400 MHz, CDCl3): δ = 8.77 (s, 1 H), 7.80-7.64 (m, 2 H), 7.60 (s, 1 H), 7.58-7.48 (m, 2 H), 6.09 (m, 1 H), 2.75-2.43 (m, 2 H), 2.40-2.18 (m, 2 H), 1.94-1.62 (m, 4 H). 13C NMR (100 MHz, CDCl3): δ = 151.0, 137.2, 134.7, 131.8, 130.0, 129.3, 129.2, 129.1, 127.0, 125.0, 123.7, 27.2, 26.2, 22.9, 22.4. HRMS: m/z calcd for C30H30N2O2Na [2 M + Na]: 473.2199; found: 473.2180.
Compound 2k: 1H NMR (400 MHz, CDCl3): δ = 8.82 (s, 1 H), 7.93 (s, 1 H), 7.88-7.78 (m, 1 H), 7.78-7.66 (m, 1 H), 7.66-7.52 (m, 2 H), 5.15 (d of AB, J = 16.5 Hz, 1 H), 4.92 (d of AB, J = 16.5 Hz, 1 H), 4.878 (t, J = 3.5 Hz, 1 H), 4.02-3.82 (m, 1 H), 3.48-3.70 (m, 1 H), 2.10-1.50 (m, 6 H). 13C NMR (100 MHz, CDCl3): δ = 146.7, 136.9, 129.8, 129.5, 129.3, 129.0, 127.3, 125.3, 121.6, 99.8, 64.1, 63.3, 31.2, 26.0, 20.3. HRMS: m/z calcd for C30H34N2O6Na [2 M + Na]: 541.2309; found: 541.2309.
General Experimental Procedure for Cyanation of 2h into 3h To a solution of 2h (19 mg, 0.094 mmol) in THF (1 mL) at r.t. was added DBU (21 µL, 0.142 mmol) and TMSCN (14 µL, 0.104 mmol), and the mixture was stirred at r.t. overnight. The mixture was directly loaded onto a silica gel column and eluted with EtOAc-hexane (1:10) to give 16.7 mg (84%) of 1-cyano-3-n-butyl-isoquinoline (3h) as a yellow solid.
Compound 3h: 1H NMR (400 MHz, CDCl3): δ = 8.38 (d, J = 8.0 Hz, 1 H), 7.94-7.82 (d, J = 8.0 Hz, 1 H), 7.82-7.65 (m, 3 H), 2.98 (t, J = 7.3 Hz, 2 H), 1.80 (quin, J = 7.3 Hz, 2 H), 1.42 (sext, J = 7.3 Hz, 2 H), 0.97 (t, J = 7.3 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 157.6, 137.3, 134.8, 132.1, 129.4, 128.5, 127.5, 125.8, 122.9, 116.7, 38.1, 32.6, 23.0, 14.5.