An Efficient Palladium Mediated Synthesis of (±)-γ-Lycorane

Abstract

An intramolecular approach incorporating a Michael ­addition followed by a palladium-mediated arylation of ketone ­towards the synthesis of Amaryllidaceae alkaloid (±)-γ-lycorane was reported.

synthesis - (±)-γ-lycorane - palladium - intramolecular arylations - alkaloids

References

<A NAME="RD18403ST-1A">1a</A> Lewis JR. Nat. Prod. Rep.  2001,  18:  95 

<A NAME="RD18403ST-1B">1b</A> Hoshino O. In The Alkaloids   Vol. 51:  Cordell GA. Academic Press; New York: 1998.  p.323-424  

<A NAME="RD18403ST-1C">1c</A> Martin SF. In The Alkaloids   Vol. 30:  Brossi A. Academic Press; New York: 1987.  p.251-376  

<A NAME="RD18403ST-2">2</A> Tang W. Hemm I. Bertram B. Planta Med.  2003,  69:  97 ; and references cited therein

<A NAME="RD18403ST-3A">3a</A> Lewis JR. Nat. Prod. Rep.  1998,  15:  107 

<A NAME="RD18403ST-3B">3b</A> Lewis JR. Nat. Prod. Rep.  1994,  11:  329 

<A NAME="RD18403ST-4A">4a</A> Jin Z. Li Z. Huang R. Nat. Prod. Rep.  2002,  19:  454 

<A NAME="RD18403ST-4B">4b</A> Padawa A. Brodney MA. Lynch SM. J. Org. Chem.  2001,  66:  1716 

<A NAME="RD18403ST-4C">4c</A> Banwell MG. Harvey JE. Hockless DCR. Wu AW. J. Org. Chem.  2000,  65:  4241 ; and references cited therein

<A NAME="RD18403ST-5">5</A> Miranda LD. Zard SZ. Org. Lett.  2002,  4:  1135 

<A NAME="RD18403ST-6">6</A> Yasuhara T. Nishimura K. Yamashita M. Fukuyama N. Yamada K. Muraoka O. Tomioka K. Org. Lett.  2003,  5:  1123 

<A NAME="RD18403ST-7">7</A> Shao Z. Chen J. Tu Y. Li L. Zhang H. Chem. Commun.  2003,  1918 

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<A NAME="RD18403ST-9">9</A> To the best of our knowledge only one total synthesis involving intramolecular arylation of ketone was made by: Muratake H. Hayakawa A. Natsume M. Chem. Pharm. Bull.  2000,  48:  1558 

Similar transformation has been used for the synthesis of Aeruginosins in:

<A NAME="RD18403ST-10A">10a</A> Valls N. Vallribera M. Carmeli S. Bonjoch J. Org. Lett.  2003,  5:  447 

<A NAME="RD18403ST-10B">10b</A> Valls N. López-Canet M. Vallribera M. Bonjoch J. Chem.-Eur. J.  2001,  7:  3446 

<A NAME="RD18403ST-11">11</A>

Compound 4: IR (KBr): ν_max = 1696 (w), 1664 (m), 1389 (m), 1216 (s), 1173 (s)cm^-1. ¹H NMR (300 MHz, CDCl₃):
δ = 5.36 (1 H, s), 4.53 (1 H, s), 3.46 (3 H, s, OMe), 2.69 (2 H, t, J = 6.7 Hz), 2.67-2.62 (4 H, brs), 2.05 (2 H, t, J = 6.7 Hz), 1.26 (2 H, brs). ¹³C NMR (75 MHz, CDCl₃): δ = 153.23, 133.15, 119.52, 90.54, 54.05, 41.09, 40.17, 29.40. GC-MS: m/z (%) = 153.4 (2) [M⁺], 152.3 (1), 138.4 (1), 136.4 (3), 135.3 (17), 125.5 (15), 123.7 (100), 121.4 (16), 120.3 (5), 109.4 (39), 108.3 (35), 105.2 (16), 103.2 (11), 91.3 (46), 79.4 (35), 77.3 (38). Compound 5: IR (KBr): ν_max = 1665 (w), 1502 (w), 1477 (s), 1413 (w), 1390 (w), 1241 (s), 1216 (s), 1172 (m), 1038 (s) cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 6.96 (1 H, s), 6.87 (1 H, s), 5.93 (2 H, s), 5.43 (1 H, s), 4.58 (1 H, s), 3.74 (2 H, s), 3.52 (3 H, s, OMe), 2.80-2.60 (6 H, m), 2.20 (2 H, t, J = 6.7 Hz). ¹³C NMR (75 MHz, CDCl₃):
δ = 153.31, 147.69, 147.61, 133.46, 133.01, 119.47, 114.38, 113.00, 110.39, 102.01, 90.65, 54.18, 53.91, 47.05, 37.36, 29.60, 29.51. GC-MS: m/z (%) = 364.4 (7) [M⁺ - 1], 362.4 (6) [M⁺ - 1], 284.4 (10), 244.2 (61), 242.2 (58), 216.3 (22), 215.0 (100), 213.1 (82), 182.9 (8), 162.4 (13), 157.2 (21), 155.2 (16), 136.5 (9), 135.2 (72), 124.4 (67), 123.3 (26), 121.4 (17), 108.4 (7), 105.4 (32). Compound 6: IR (KBr): ν_max = 1713 (s), 1503 (w), 1478 (s), 1411 (w), 1360 (m), 1223 (s) cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 6.92 (1 H, s), 6.83 (1 H, s), 5.92 (1 H, d, J = 1.0 Hz), 5.91 (1 H, d, J = 1.0 Hz), 3.76 (1 H, d, J = 13.8 Hz), 3.28 (1 H, d, J = 13.8 Hz), 2.91 (1 H, dd, J = 8.3, 17.0 Hz), 2.87 (1 H, dd, J = 4.3, 10.3 Hz), 2.55 (1 H, td, J = 4.2, 15.8 Hz), 2.52 (1 H, td, J = 4.2, 15.8 Hz), 2.51 (1 H, dd, J = 4.3, 15.7 Hz), 2.44 (1 H, ddd, J = 4.7, 10.3, 18.0 Hz), 2.18 (1 H, ddd, J = 4.5, 6.5, 18.0 Hz), 2.10 (1 H, dd, J = 9.7, 17.0 Hz), 2.02-1.90 (2 H, m), 1.76-1.68 (1 H, m), 1.55-1.45 (1 H, m). ¹³C NMR (75 MHz, CDCl₃): δ = 212.74, 147.73, 147.53, 131.93, 114.33, 112.71, 110.71, 101.96, 62.20, 57.20, 53.50, 41.93, 36.48, 35.52, 29.83, 26.71. GC-MS: m/z (%) = 353.4 (37) [M⁺], 351.2 (42) [M⁺], 296.3 (45), 294.1 (54), 281.3 (6), 272.3 (8), 213.3 (100), 185.0 (11), 159.2 (8), 157.1 (34), 154.9 (15), 148.4 (11), 135.3 (47). Compound 7: IR (KBr): ν_max = 2927 (w), 2788 (w), 1730 (m), 1715 (s), 1645 (w), 1503 (m), 1484 (s), 1448 (w), 1373 (w), 1241 (s), 1145 (w), 1100 (w), 1039 (s), 935 (m), 807 (m)cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 6.60 (1 H, s), 6.50 (1 H, s), 5.91 (1 H, d, J = 1.3 Hz), 5.90 (1 H, d, J = 1.3 Hz), 3.99 (1 H, d, J = 14.5 Hz, PhCH), 3.46 (1 H, d, J = 3.6 Hz), 3.28 (1 H, d, J = 14.5 Hz, PhCH), 3.22 (1 H, dd, J = 7.9, 8.6 Hz), 2.83 (1 H, dd, J = 3.6, 7.8 Hz), 2.71-2.63 (1 H, m), 2.53 (1 H, ddd, J = 4.3, 10.8, 15.4 Hz), 2.39 (1 H, ddd, J = 4.5, 6.5, 10.8 Hz), 2.22 (1 H, dd, J = 8.6, 17.4 Hz), 2.13-2.03 (2 H, m), 1.85-1.76 (1 H, m), 1.69-1.60(1 H, m). ¹³C NMR (75 MHz, CDCl₃): δ = 209.84, 147.02, 146.04, 128.40, 125.04, 111.81, 106.42, 101.19, 64.39, 56.19, 54.12, 51.46, 36.59, 34.97, 29.35, 27.20. GC-MS: m/z (%) = 271.4 (64) [M⁺], 270.4 (100), 255.5 (5), 254.4 (35), 243.4 (3), 242.4 (18), 241.4 (3), 228.4 (7), 225.4 (2), 215.4 (6), 214.4 (21), 212.3 (15), 207.3 (11), 200.4 (5), 188.4 (7), 187.4 (17), 184.4 (5), 174.3 (13), 173.3 (6), 162.4 (14), 154.3 (9), 148.3 (12), 147.3 (10), 130.4 (11), 116.4 (8), 115.3 (10), 106.4 (5), 102.3 (12), 91.4 (7), 89.3 (17), 78.3 (10), 77.4 (24).

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