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Reactivity of (3-Methylpentadienyl)iron(1+) Cation: Late-stage Introduction of a (3-Methyl-2Z,4-pentadien-1-yl) Side Chain

Subhabrata Chaudhury, Shukun Li, William A. Donaldson


The 3-methyl-2Z,4-pentadien-1-yl sidechain is found in various sesquiterpenes and diterpenes. A route for the late stage introduction of this functionality was developed which relies on nucleophilic attack on the (3-methylpentadienyl)iron(1+) cation, followed by oxidative decomplexation.  This methodology was applied to the synthesis of the proposed structure of heteroscyphic acid A methyl ester.  Realization of this synthesis led to a correction of the proposed structure.

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- R. Takeda, R. Mori and Y. Hirose, Chem. Lett. 1982, 1625-1628. R. Takeda, H. Naoki, T. Iwashita, K. Mizukawa, Y. Hirose and M. Inoue, Bull. Chem. Soc. Jpn. 1983, 1125-1132.

- J. Li, L. Pan, J. N. Fletcher, W. Lv, Y. Deng, M. A. Vincent, J. P. Slack, T. S. McCluskey, Z. Jia, M. Cushman and A. Douglas Kinghorn, J. Nat. Prod. 2014, 77, 1739-1743.

- C. Gaspar-Marques, M. F. Simoes and B. Rodriguez, J. Nat. Prod. 2004, 67, 614-621.

- S. Kanokmedhakul, K. Kanokmedhakul and M. Buayairaksa, J. Nat. Prod. 2007, 70, 1122-1126.

- For other examples of diterpenes containing a 3-methyl-2Z,4-pentadien-1-yl) side chain see: (a) T. Ohtsuki, T. Koyano, T. Kowithayakorn, N. Yamaguchi and M. Ishibashi, Planta Med. 2004, 70, 1170-1173. (b) C. Gaspar-Marques, M. F. Simoes, A. Duarte and B. Rodriguez, J. Nat. Prod. 2003, 66, 491-496. (c) J. A. Garbarino and A. Molinari, J. Nat. Prod. 1993, 56, 624-626. (d) S. Kanokmedhakul, K. Kanokmedhakul, T. Kanarsa and M. Buayairaksa, J. Nat. Prod. 2005, 68, 183-188. (e) M. S. Hunter, D. G. Corley, C. P. Carron, E. Rowold, B. F. Kilpatrick and R. C. Durley, J. Nat. Prod. 1997, 60, 894-899.

- P. Bremond, N. Vanthuyne and G. Audran, Tetrahedron Lett. 2009, 50, 5723-5725.

- (a) W. A. Donaldson and S. Chaudhury, Eur. J. Org. Chem. 2009, 3831-3843. (b) W. A. Donaldson, Curr. Org. Chem. 2000, 4, 851-882.

- (a) S. Chaudhury, S. Li and W. A. Donaldson, Chem. Commun. 2006, 2069-2070. (b) S. Chaudhury, S. Li, D. W. Bennett, T. Siddiquee, D. T. Haworth and W. A. Donaldson, Organometallics 2007, 26, 5295-5303.

- (a) K. Nabeta, T. Oohata, N. Izumi and K. Katoh, Phytochemistry 1994, 37, 1263-1268. (b) K. Nabeta, T. Ishikawa, T. Kawae and H. Okuyama, J. Chem. Soc., Chem. Commun. 1995, 651-652. (c) K. Nabeta, T. Ishikawa and H. Okuyama, J. Chem. Soc., Perkin Trans. 1 1995, 3111-3115.

- D. L. Boger and R. J. Mathvink, J. Org. Chem. 1992, 58, 1429-1443.

- P. A. Zoretic, M. Ramchandani and M. L. Caspar, Synth. Commun. 1991, 21, 915-922.

- M. Liapis and V. Ragoussis, J. Chem. Soc., Perkin Trans. 1 1985, 815-817.

- R. M. Coates and J. E. Shaw, J. Org. Chem. 1970, 35, 2601-2605.

- E. Wenkert, A. Afonso, P. Beak, J. W. J. Carney, P. W. Jeffs and J. D. McChesney, J. Org. Chem. 1965, 30, 713-722.

- M. Czarny, K. K. Maheshwari, J. A. Nelson and T. A. Spencer, J. Org. Chem. 1975, 40, 2079-2085. (b) E. Wenkert, A. Afonso, J. Bredenberg, C. Kaneko and A. Tahara, J. Am. Chem. Soc. 1964, 86, 2038-2043.

- (a) T. Ling, C. Chowdhury, B. Kramer, B. G. Vong, M. Palladino and E. A. Theodorakis, J. Org. Chem. 2002, 66, 8843-8853. (b) S. C. Welch, C. P. Hagan, J. H. Kim and P. S. Chu, J. Org. Chem. 1977, 42, 2879-2887. (c) S. C. Welch, C. P. Hagan, W. P. Fleming and J. W. Trotter, J. Am. Chem. Soc. 1977, 99, 549-556.

- (a) M. Furlan, M. N. Lopes, J. B. Fernandes and J. R. Pirani, Phytochemistry 1996, 41, 1159-1161. (b) D. Herlem, F. Khuong-Huu and A. S. Kende, Tetrahedron 1994, 50, 2055-2070. (c) A. F. Barrero, J. F. Sanchez, J. Altarejos, A. Perales and R. Torres, Phytochemistry, 1992, 31, 615-620. (d) J. Bastard, D. K. Duc, M. Fetizon, M. J. Francis, P. K. Grant, R. T. Weavers, C. Kaneko, G. V. Baddeley, J. M. Bernassau, R. R. Burfitt, P. M. Wuvkulich and E. Wenkert, J. Nat. Prod. 1984, 47, 592-599.

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