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A. G. K. Reddy et al.
LETTER
(15) Goodman, A. J.; Le Bourdonnec, B.; Dolle, R. E.
ChemMedChem. 2007, 2, 1552.
(16) Brossi, A.; Grethe, G.; Teitel, S.; Wildman, W. C.; Bailey,
D. T. J. Org. Chem. 1970, 35, 1100.
(17) Kobayashi, S.; Tokumoto, T.; Taira, Z. J. Chem. Soc., Chem.
Commun. 1984, 1043.
OC=O), 138.13 (s, ArC), 135.19 (s, ArC), 131.58 (s, ArC),
129.31 (d, ArC), 129.05 (d, 2 C, ArC), 128.32 (d, 2 C, ArC),
127.25 (d, ArC),126.92 (d, ArC), 126.75 (d, ArC), 126.31 (d,
ArC), 62.31 (t, NCH2), 60.95 (t, OCH2CH3), 56.11 (t,
NCH2), 52.95 (t, C-3¢), 45.46 (d, C-4¢), 14.22 (q, OCH2CH3)
ppm.
(18) Canadine synthesis: Matulenko, M. A.; Meyers, A. I. J. Org.
Chem. 1996, 61, 573.
(19) Synthesis of stepharinine and pronuciferine: Honda, T.;
Shigehisa, H. Org. Lett. 2006, 8, 657.
(20) Erythrocarine isolation: Chawla, A. S.; Redha, F. M. J.;
Jackson, A. H. Phytochemistry 1985, 24, 1821.
(21) 6,6a-Dihydrodemethoxygaudiscine isolation: .
(22) Costa, E. V.; Marques, F. A.; Pinheiro, M. L. B.; Vaz, N. P.;
Duarte, M. C. T.; Delarmelina, C.; Braga, R. M.; Sales Maia,
B. H. L. N. J. Nat. Prod. 2009, 72, 1516.
(23) Chandrasekhar, S.; Reddy, N. R.; Rao, Y. S. Tetrahedron
Lett. 2006, 62, 12098.
(24) (a) Escalante, J.; Carrillo-Morales, M.; Linzaga, I.
Molecules 2008, 13, 340. (b) Roy, O.; Faure, S.; Thery, V.;
Didierjean, C.; Taillefumier, C. Org. Lett. 2008, 10, 921.
(25) General Procedure for Buchwald–Hartwig Cyclization:
The following Procedure for 4a is Representative
In an oven-dried Schlenk tube under nitrogen atmosphere
were taken Pd(OAc)2 (10 mol%), Ph3P (20 mol%), and
Cs2CO3 (2 mmol) in toluene (ca. 1.5 mL), and the mixture
was stirred for 5 min. To this mixture was added ester 3a (1
mmol) in toluene (ca. 3.0 mL), and the reaction mixture was
stirred for 24 h at 80 °C. Progress of the reaction was
monitored by TLC, and, after the reaction is complete, it was
quenched by addition of aq NH4Cl and extracted with
CH2Cl2 (3 × 20 mL). The organic layer was dried over
Na2SO4, filtered, and concentrated under reduced pressure.
Purification of the residue by column chromatography on
silica gel using PE–EtOAc as eluent furnished the product 4a
in 82% yield.
Compound 4b: 79% yield. IR: 2931, 2828, 1729, 1610,
1514, 1455, 1252, 1134, 1031, 741 cm–1. 1H NMR (400
MHz, CDCl3): d = 7.41–7.24 (m, 5 H, ArH), 6.74 (s, 1 H,
ArH), 6.52 (s, 1 H, ArH), 4.26–4.06 (m, 2 H, OCH2CH3),
3.85 (s, 3 H, ArOCH3), 3.83 (s, 3 H, ArOCH3), 3.78 (dd, 1
H, J = 5.0, 5.0 Hz, 4¢-H), 3.74 [d, 1 H, J = 13.1 Hz,
NCH2(a¢,b¢)], 3.67 [d, 1 H, J = 14.5 Hz, NCH2(a,b)], 3.65 [d,
1 H, J = 13.1 Hz, NCH2(a¢,b¢)], 3.52 [d, 1 H, J = 14.5 Hz,
NCH2(a,b)], 3.17 (dd, 1 H, J = 11.4, 5.5 Hz,
NCH2aCHCOOEt), 2.85 (dd, 1 H, J = 11.4, 4.8 Hz,
NCH2bCHCOOEt), 1.22 (t, 3 H, J = 7.1 Hz, OCH2CH3)
ppm. 13C NMR (100 MHz, CDCl3): d = 173.3 (s, OC=O),
148.1 (s, ArC), 147.48 (s, ArC), 138.10 (s, ArC), 129.05 (d,
2 C, ArC), 128.29 (d, 2 C, ArC), 127.36 (s, ArC), 127.22 (d,
ArC), 123.27 (s, ArC), 111.82 (d, ArC), 109.22 (d, ArC),
62.23 (t, NCH2), 60.87 (t, OCH2CH3), 55.92 (q, ArOCH3),
55.83 (q, ArOCH3), 55.66 (t, NCH2), 52.98 (t, C-3¢), 44.91
(d, C-4¢), 14.24 (q, OCH2CH3) ppm. HRMS (ESI+): m/z
calcd for [C21H25NNaO4]+ = [M + Na]+: 378.1676; found:
378.1685.
Compound 4c: 85% based on the recovery of 19% of starting
material. IR: 2938, 2834, 1732, 1598, 1458, 1238, 1118, 741
cm–1. 1H NMR (400 MHz, CDCl3): d = 7.42–7.20 (m, 5 H,
ArH), 6.35 (s, 1 H, ArH), 4.25–4.00 (m, 2 H, OCH2CH3),
3.87 (s, 3 H, ArOCH3), 3.83 (s, 3 H, ArOCH3), 3.81 (s, 3 H,
ArOCH3), 3.80–3.67 (m, 1 H, 4¢-H), 3.74 [d, 1 H, J = 14.8
Hz, NCH2(a,b)], 3.72 [d, 1 H, J = 13.2 Hz, NCH2(a¢,b¢)],
3.70 [d, 1 H, J = 14.8 Hz, NCH2(a,b)], 3.60 [d, 1 H, J = 13.2
Hz, NCH2(a¢,b¢)], 3.08 (dd, 1 H, J = 11.5, 5.1 Hz,
NCH2aCHCOOEt), 2.81 (dd, 1 H, J = 11.5, 5.1 Hz,
NCH2bCHCOOEt), 1.20 (t, 3 H, J = 7.2 Hz, OCH2CH3)
ppm. 13C NMR (100 MHz, CDCl3): d = 173.86 (s, OC=O),
152.79 (s, ArC), 151.54 (s, ArC), 140.05 (s, ArC), 138.05 (s,
ArC), 130.75 (s, ArC), 128. 94 (d, ArC), 128.59 (s, ArC),
128.30 (d, ArC), 127.22 (d, ArC), 118.36 (s, ArC), 104.82
(d, ArC), 61.98 (t, NCH2), 60.71 (q, ArOCH3), 60.69 (t,
NCH2), 60.33 (q, ArOCH3), 55.90 (t, 2 C, OCH2CH3 and
OCH3), 53.48 (t, NCH2CHCOOEt), 41.27 (d,
Representative Analytical Data
Compound 4a: IR: 3027, 2982, 1732, 1684, 1452, 1242,
1166, 1034, 741 cm–1. 1H NMR (400 MHz, CDCl3): d =
7.36–7.10 (m, 8 H, ArH), 7.06–6.98 (m, 1 H, ArH), 4.20–
4.10 (m, 2 H, OCH2CH3), 3.85 (dd, 1 H, J = 5.2, 5.2 Hz,
4¢-H), 3.80 [d, 1 H, J = 14.9 Hz, NCH2 (a,b)], 3.74 [d, 1 H,
J = 13.2 Hz, NCH2 (a¢,b¢)], 3.65 [d, 1 H, J = 13.2 Hz, NCH2
(a¢,b¢)], 3.59 [d, 1 H, J = 14.9 Hz, NCH2(a,b)], 3.18 (dd,
J = 11.5, 5.6 Hz, 1 H, NCH2aCHCOOEt), 2.85 (dd, J = 11.5,
4.8 Hz, 1 H, N-CH2bCHCOOEt), 1.23 (t, J = 7.2 Hz, 3 H,
OCH2CH3) ppm. 13C NMR (50 MHz, CDCl3): d = 173.25 (s,
NCH2CHCOOEt), 14.23 (q, OCH2CH3) ppm. HRMS
(ESI+): m/z calcd for [C22H27NNaO4]+ = [M + Na]+:
408.1781; found: 408.1787.
Synlett 2011, No. 12, 1756–1760 © Thieme Stuttgart · New York