Download PDF
Synlett 2007(15): 2363-2366  
DOI: 10.1055/s-2007-985596
LETTER
© Georg Thieme Verlag Stuttgart · New York

Application of the Hypervalent Iodine Reagent to the Synthesis of Some Pentasubstituted Aporphine Alkaloids

Ratchanok Pingaewa, Somsak Ruchirawat*a,b,c
a Department of Chemistry, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand
b Chulabhorn Research Institute and Chulabhorn Graduate Institute, Vipavadee Rangsit Highway, Bangkok 10210, Thailand
c Program on Research and Development of Synthetic Drugs, Institute of Science and Technology for Research and Development, Mahidol University, Salaya Campus, Salaya 73170, Thailand
Fax: +66(2)5740616; e-Mail: somsak@cri.or.th;
Further Information

Publication History

Received 25 June 2007
Publication Date:
22 August 2007 (online)

    Permissions and Reprints All articles of this category

Abstract

The oxidative biaryl coupling of various N-substituted 1-benzyltetrahydroisoquinolines to the corresponding aporphines by the hypervalent iodine reagent was studied. The study sheds light on the unifying mechanism of the reaction illustrating the requirement of the p-p coupling via the six-membered transition state as the ­initial step. The finding was applied to the synthesis of some pentasubstituted aporphine alkaloids.

Key words

aporphine - 1-benzyltetrahydroisoquinoline - neospirinedienone - hypervalent iodine - p-p coupling

35

Typical Procedure: To a stirred solution of N-formyl-tetrahydroisoquinoline 2g (150 mg, 0.40 mmol) in CH2Cl2 (10 mL) was added a solution of bis(trifluoroacetoxy)iodo-benzene (191 mg, 0.44 mmol) and BF3·ΟEt2 (0.12 mL, 0.88 mmol) in CH2Cl2 (5 mL) at -40 °C under an argon atmosphere. The reaction mixture was stirred at -40 °C for 1 h, then sat. NaHCO3 (30 mL) was added followed by extraction with CH2Cl2 (3 × 30 mL). The combined CH2Cl2 extracts were dried over anhyd Na2SO4 and evaporated to dryness in vacuo. The crude product was purified by PLC on silica gel using 50% EtOAc-hexane as a developing solvent to give aporphine 1g (62 mg, 42%). Recrystallization from EtOAc afforded yellow needles; mp 193.0-193.6 °C. IR (nujol): 1675, 1602, 1570, 1520 cm-1. 1H NMR (300 MHz, CDCl3): δ = 2.60-3.42 (m, 5 H, C4-H2, C5-H, C7-H2), 3.88-3.95, 4.43-4.47 (2 × m, 1 H, C5-H), 3.86, 3.93, 3.95, 3.99, 4.00 (5 × s, 12 H, 4 × OMe), 4.59-4.64, 4.95-5.06 (2 × m, 1 H, C6a-H), 6.79, 6.82 (2 × s, 1 H, C8-H), 7.08, 7.12 (2 × s, 1 H, C1-H), 7.20 (s, 1 H, C11-H), 8.30, 8.42 (2 × s, 1 H, CHO). 13C NMR (75 MHz, CDCl3): δ = 23.73, 24.78 (C-4), 32.75, 36.77 (C-7), 36.02, 42.03 (C-5), 49.30, 53.06 (C-6a), 55.90, 56.00, 56.13, 56.34, 60.56, 60.66 (4 × OMe), 106.64, 106.78 (C-1), 107.09, 107.19 (C-11), 111.67, 112.06 (C-8), 123.43, 123.75, 125.90, 126.17, 126.92, 127.77, 128.08, 128.91, 130.12, 130.46 (C-1a, C-1b, C-3a, C-7a, C-11a), 145.10, 145.55 (C-3), 148.31, 148.65 (C-10), 148.83, 148.92 (C-9), 151.54, 151.86 (C-2), 161.89, 162.22 (CHO). LRMS (EI): m/z (%) = 369 (8.28) [M]+, 337 (100.00), 309 (72.14). HRMS (FAB): m/z [M + H]+ calcd for C21H24NO5: 370.1654; found: 370.1661. Anal. Calcd for C21H23NO5: C, 68.28; H, 6.28; N, 3.79. Found: C, 68.29; H, 5.94; N, 3.70. Neospirinedienone 3e (130 mg, 91%) was obtained following the above procedure starting from isoquinoline 1e (150 mg, 0.40 mmol); mp 242.3-243.8 °C. IR (nujol): 1663, 1647, 1623, 1588, 1513 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.93-2.28 (m, 2 H, C5-H2), 2.83-3.36 (m, 2 H, C8-H2), 3.26-3.81 (m, 2 H, C6-H2), 3.69, 3.71, 3.89, 3.90 (4 × s, 9 H, 3 × OMe), 4.26 (dd, J = 4.6, 8.1 Hz, 1 H, C7a-H), 4.54 (dd, J = 2.5, 6.1 Hz, 1 H, C7a-H), 5.81, 5.86 (2 × s, 1 H, C4-H), 6.50, 6.62 (2 × s, 1 H, C1-H), 6.66, 6.67 (2 × s, 1 H, C9-H), 6.95, 7.02 (2 × s, 1 H, C12-H), 8.30, 8.48 (2 × s, 1 H, CHO). 13C NMR (75 MHz, CDCl3): δ = 32.11, 34.96 (C-8), 38.67, 40.99 (C-5), 41.68, 44.91 (C-6), 47.98, 49.23 (C-4a), 55.12, 55.18, 56.00, 56.04 (3 × OMe), 56.89, 59.32 (C-7a), 107.82, 107.98 (C-12), 110.67, 111.16 (C-9), 116.04, 117.87 (C-4), 123.15, 123.62 (C-1), 124.14, 126.18 (C-12a), 127.00, 128.16 (C-8a), 148.47, 148.61, 150.73, 151.18, 151.38, 151.75 (C-3, C-10, C-11), 156.13, 157.98 (C-1a), 160.59, 160.85 (CHO), 180.80, 180.92 (C-2). LRMS (EI): m/z (%) = 355 (47.82) [M]+, 327 (50.32), 297 (100.00).