Transfer Hydrogenation of Isoquinolinium Salts Catalyzed by a Rhodium Complex

Abstract

Regio- and chemoselective transfer hydrogenation of isoquinolinium salts catalyzed by [Cp*RhCl₂]₂ using HCOOH-Et₃N (5:2) as a hydrogen source was realized. A variety of N-methyl- and N-benzyl-1,2,3,4-tetrahydroisoquinoline alkaloids were obtained in high yields by the present catalyst system.

Key words

transfer hydrogenation - rhodium(III) complex - isoquinoline - isoquinolinium salt - tetrahydroisoquinoline

References and Notes

• The reviews for synthesis of tetrahydroisoquinolines, see:
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• 2a Glorius F. Org. Biomol. Chem.  2005,  3:  4171 ; and references cited therein
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• 7a

  No product was observed when isoquinoline was refluxed in MeCN catalyzed by [Cp*RhCl₂]₂ with 5:2 formic acid-Et₃N azeotropic mixture.

• 7b Watanabe Y. Ohta T. Tsuji T. Hiyoshi T. Tsuji T. Bull. Chem. Soc. Jpn.  1984,  57:  2440 
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12

General Procedure.
To a solution of 1 (0.5 mmol) and [Cp*RhCl₂]₂ (0.0025 mmol) in CH₂Cl₂ (1.5 mL) under an atmosphere of argon was added a 5:2 formic acid-Et₃N azeotropic mixture (0.125 mL). The resulting mixture was stirred at 40 °C for a certain period of time, made basic by addition of aq Na₂CO₃, and then extracted with CH₂Cl₂. Purification on silicon gel afforded the desired products 2, which were characterized by ¹H NMR, ¹³C NMR and IR spectroscopy, and HRMS. The data of unknown compounds was shown as the following:
Compound 2a: colorless oil. IR: 3061, 3024, 2916, 2799, 1602, 1495, 1464, 1453, 739 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 2.80 (t, J = 5.9 Hz, 2 H), 2.96 (t, J = 5.8 Hz, 2 H), 3.70 (s, 2 H), 3.74 (br s, 2 H), 7.04 (br s, 1 H), 7.12-7.17 (m, 3 H), 7.31-7.47 (m, 5 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 29.1, 50.6, 56.1, 62.7, 125.5, 126.0, 126.5, 127.0, 128.2, 128.6, 129.0, 134.3, 134.8, 138.3 ppm. HRMS (ESI): m/z calcd for C₁₆H₁₇N [M + H]: 224.1434; found: 224.1443.
Compound 2b: colorless oil. IR: 3061, 3024, 2968, 2925, 2804, 1603, 1582, 1493, 1452, 1365, 757 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.48 (d, J = 6.7 Hz, 3 H), 2.74-2.83 (m, 2 H), 2.91-3.06 (m, 1 H), 3.13-3.16 (m, 1 H), 3.78 (d, J = 13.6 Hz, 1 H), 3.90 (d, J = 13.6 Hz, 1 H), 3.97 (q, J = 6.7 Hz, 1 H), 7.13-7.22 (m, 4 H), 7.33-7.49 (m, 5 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 19.7, 27.4, 43.8, 56.2, 58.2, 125.6, 125.8, 126.8, 127.4, 128.2, 128.7, 128.8, 134.3, 139.5, 140.4 ppm. HRMS (ESI): m/z calcd for C₁₇H₁₉N [M + H]: 238.1590; found: 238.1593.
Compound 2c: colorless oil. IR: 3058, 3024, 2991, 2930, 2867, 2830, 2803, 1607, 1513, 1492, 1462, 1353, 741 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.20 (d, J = 6.4 Hz, 3 H), 2.66 (dd, J = 5.8, 16.2 Hz, 1 H), 3.03-3.20 (m, 2 H), 3.62 (d, J = 13.2 Hz, 1 H), 3.66 (d, J = 15.7 Hz, 1 H), 3.75 (d, J = 15.8 Hz, 1 H), 3.87 (d, J = 13.2 Hz, 1 H), 6.90-7.00 (m, 1 H), 7.12-7.15 (m, 3 H), 7.29-7.44 (m, 5 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 15.1, 35.5, 51.5, 52.1, 57.2, 125.5, 126.0, 126.4, 126.9, 128.2, 128.8, 128.9, 134.0, 134.4, 139.4 ppm. HRMS (ESI): m/z calcd for C₁₇H₁₉N [M + H]: 238.1590; found: 238.1579.
Compound 2e: yellow oil. IR: 2921, 2832, 1610, 1575, 1524, 1452, 1465, 821, 800, 771, 733, 699 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 2.76 (t, J = 5.9 Hz, 2 H), 3.18 (t, J = 5.9 Hz, 2 H), 3.69 (s, 2 H), 3.70 (s, 2 H), 7.24-7.26 (m, 2 H), 7.29-7.41 (m, 5 H), 7.80-7.83 (m, 1 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 27.2, 49.9, 56.0, 62.5, 122.8, 126.1, 127.4, 128.4, 129.0, 130.3, 131.7, 137.6, 138.0 ppm. HRMS (ESI): m/z calcd for C₁₆H₁₇N₂O₂ [M + H]: 269.1285; found: 269.1281.
Compound 2g: light yellow oil. IR: 3058, 3024, 2991, 2929, 2867, 2830, 1607, 1513, 1492, 1462, 730 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 0.96 (t, J = 7.3 Hz, 3 H), 1.73-1.79 (m, 2 H), 2.46-2.54 (m, 1 H), 2.73-2.84 (m, 2 H), 3.13-3.18 (m, 1 H), 3.46 (t, J = 6.2 Hz, 1 H), 3.69 (d, J = 13.5 Hz, 1 H), 3.80 (d, J = 13.5 Hz, 1 H), 3.85 (s, 3 H), 3.87 (s, 3 H), 6.54 (s, 1 H), 6.59 (s, 1 H), 7.24-7.41 (m, 5 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 10.9, 24.2, 29.0, 43.6, 55.7, 55.9, 57.8, 61.9, 110.6, 111.2, 126.5, 126.7, 128.1, 128.8, 130.6, 140.0, 147.1 ppm. HRMS (ESI): m/z calcd for C₂₀H₂₅NO₂ [M + H]: 312.1958; found: 312.1968.
Compound 2h: light yellow oil. IR: 2950, 2904, 2867, 2831, 1608, 1513, 1463, 1375, 1358, 770 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 0.85 (d, J = 6.8 Hz, 3 H), 0.98 (d, J = 6.8 Hz, 3 H), 1.85-1.92 (m, 1 H), 2.42 (s, 3 H), 2.57-2.69 (m, 3 H), 3.09-3.17 (m, 2 H), 3.82 (s, 3 H), 3.83 (s, 3 H), 6.53 (s, 1 H), 6.56 (s, 1 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 20.0, 20.1, 25.4, 34.3, 44.1, 48.2, 55.7, 55.8, 69.4, 111.0, 111.8, 127.4, 128.7, 146.3, 147.0 ppm. HRMS (ESI): m/z calcd for C₁₅H₂₄NO₂ [M + H]: 250.1802; found: 250.1805.
Compound 2i: white solid; mp: 80-81 °C. IR: 3022, 2946, 2907, 2832, 1607, 1513, 1488, 1463, 1451, 1364, 741, 716 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 2.24 (s, 3 H), 2.57-2.65 (m, 1 H), 2.71-2.78 (m, 1 H), 3.06-3.22 (m, 2 H), 3.56 (s, 3 H), 3.85 (s, 3 H), 4.18 (s, 1 H), 6.09 (s, 1 H), 6.60 (s, 1 H), 7.22-7.34 (m, 5 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 28.9, 44.2, 52.2, 55.7, 71.0, 110.6, 111.4, 126.5, 127.3, 128.2, 129.5, 130.3, 143.8, 147.0, 147.3 ppm. HRMS (ESI): m/z calcd for C₁₈H₂₂NO₂ [M + H]: 284.1645; found: 284.1639.
Compound 2k: light yellow oil. IR: 3024, 2964, 2918, 2838, 1588, 1494, 1454, 1443, 1370, 735 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.17 (d, J = 6.1 Hz, 3 H), 2.42 (s, 3 H), 2.61-2.72 (m, 2 H), 2.80-2.88 (m, 1 H), 3.57 (d, J = 15.4 Hz, 1 H), 3.83 (d, J = 15.4 Hz, 1 H), 7.00-7.15 (m, 4 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 17.9, 36.7, 41.4, 54.8, 57.2, 125.5, 126.0, 128.4, 134.0, 134.4 ppm. HRMS (ESI): m/z calcd for C₁₁H₁₅N [M + H]: 162.1277; found: 162.1282.