Model Studies Toward the Enantioselective Synthesis of Perhydrohistrionicotoxin: A Free-Radical Approach to the Azaspirocycle Core

Eduardo Peralta-Hernández; Alejandro Cordero-Vargas

doi:10.1055/s-0035-1562612

Synthesis, Table of Contents

Synthesis 2016; 48(23): 4237-4245
DOI: 10.1055/s-0035-1562612

paper

Model Studies Toward the Enantioselective Synthesis of Perhydrohistrionicotoxin: A Free-Radical Approach to the Azaspirocycle Core

Eduardo Peralta-Hernández

Instituto de Química, Universidad Nacional Autónoma de México, Circuito exterior s/n, Ciudad Universitaria, C.P. 04510, Ciudad de México, México Email: acordero@unam.mx

,

Alejandro Cordero-Vargas*

Instituto de Química, Universidad Nacional Autónoma de México, Circuito exterior s/n, Ciudad Universitaria, C.P. 04510, Ciudad de México, México Email: acordero@unam.mx

› Author Affiliations

Abstract

All articles of this category

Abstract

A free-radical-based protocol for the construction of the azaspirocyclic core of the natural product perhydrohistrionicotoxin is described. The adopted strategy is based on the use of an enantiomerically pure allylamine bearing a properly substituted cyclohexane at the allylic position as a radical acceptor. An unexpected reductive atom transfer radical addition reaction, followed by lactamization and removal of the chiral auxiliary is achieved in a single manipulation.

Key words

azaspirocyclic - atom transfer radical addition (ATRA) - perhydrohistrionicotoxin - Ellman sulfinyl imines - reductive ATRA reaction

Full Text

References

References

1a Daly JW, Karle I, Myers CW, Tokuyama T, Waters JA, Witkop B. Proc. Natl. Acad. Sci. U.S.A. 1971; 68: 1870
1b Witkop B, Gössinger E In The Alkaloids . Brossi A. Academic Press; New York: 1983: 139-251
1c Takahashi K, Witkop B, Brossi A, Maleque MA, Albuquerque EX. Helv. Chim. Acta 1982; 65: 252

2a Carey SC, Aratani M, Kishi Y. Tetrahedron Lett. 1985; 26: 5887
2b Karatholuvhu MS, Sinclair A, Newton AF, Alcaraz M.-L, Stockman RA, Fuchs PL. J. Am. Chem. Soc. 2006; 128: 12656
2c Adachi, Kamei N, Yokoshima S, Fukuyama T. Org. Lett. 2011; 13: 4446

3 For a review of the synthetic strategies for the synthesis of the histrionicotoxin family of alkaloids, see: Sinclair A, Stockman RA. Nat. Prod. Rep. 2007; 24: 298
4 Corey EJ, Arnett JF, Widiger GN. J. Am. Chem. Soc. 1975; 97: 430
5 Wilson MS, Padwa A. J. Org. Chem. 2008; 73: 9601
6 Tanner D, Sellén M, Bäckvall JE. J. Org. Chem. 1989; 54: 3374
7 Keck GE, Yates JB. J. Org. Chem. 1982; 47: 3590
8 Godleski SA, Heacock DJ, Meinhart JD, Van Wallendael S. J. Org. Chem. 1983; 48: 2101
9 Duhamel P, Kotera M, Monteil T, Marabout B. J. Org. Chem. 1989; 54: 4419

10a Kim D, Shim PJ, Lee J, Park CW, Hong SW, Kim S. J. Org. Chem. 2000; 65: 4864
10b Deyine A, Poirer J.-M, Duhamel P. Synlett 2008; 260
10c Tanner D, Hagberg L, Poulsen A. Tetrahedron 1999; 55: 1427
10d Coote SC, Moore SP, O’Brien P, Withwood AC, Gilday J. J. Org. Chem. 2008; 73: 7852

11 Winkler JD, Hershberger PM. J. Am. Chem. Soc. 1989; 111: 4852
12 Tanner D, Hagberg L. Tetrahedron 1998; 54: 7907
13 Diedrichs N, Krelaus R, Gedrath I, Westermann B. Can. J. Chem. 2002; 80: 686
14 Brasholz M, Macdonald JM, Saubern S, Ryan JH, Holmes AB. Chem. Eur. J. 2010; 16: 11471
15 Peralta-Hernández E, Cortezano-Arellano O, Cordero-Vargas A. Tetrahedron Lett. 2011; 52: 6899
16 León-Rayo DF, Morales-Chamorro M, Cordero-Vargas A. Eur. J. Org. Chem. 2016; 1739

17a Yoshida M, Komatsuzaki Y, Ihara M. Org. Lett. 2008; 10: 2083
17b Imada Y, Yuassa M, Nakamura I, Murahashi S.-I. J. Org. Chem. 1994; 59: 2282

18 Prusov E, Maier ME. Tetrahedron 2007; 63: 10486

Although benzylamines are usually stable under these conditions, there are some reports of oxidative debenzylation with CAN or DDQ, where a free radical is presumably an intermediate, see:

19a Bull SD, Davies SG, Fenton G, Mulvaney AW, Prasad RS, Smith AD. J. Chem. Soc., Perkin Trans. 1 2000; 3765
19b Sampson PB, Honek JF. Org. Lett. 1999; 1: 1395

20a Mimura M, Hayashida M, Nomiyama K, Ikegami S, Iida Y, Tamura M, Hiyama Y, Ohishi Y. Chem. Pharm. Bull. 1993; 41: 1971
20b Guindon Y, Liu Z, Jung G. J. Am. Chem. Soc. 1997; 119: 9289
20c Rapoport H, Chen Y, Mohareb RM, Ahn JH, Sim TB, Ho JZ. Chem. Pharm. Bull. 2003; 51: 1153
20d Tong HM, Martin M.-T, Chiaroni A, Bénéchie M, Marazano C. Org. Lett. 2005; 7: 2437
20e Almahli H, Hendra F, Troufflard C, Cavé C, Joseph D, Delarue-Cochin S. Chirality 2011; 23: 265

21 Lifchits O, Mahlau M, Reisinger CM, Lee A, Farès C, Polyak I, Gopakumar G, Thiel W, List B. J. Am. Chem. Soc. 2013; 135: 6677

22a Robak MT, Herbage MA, Ellman JA. Chem. Rev. 2010; 110: 3600
22b Ellman JA. Pure Appl. Chem. 2003; 75: 39
22c Ellman JA, Owens TD, Tang TP. Acc. Chem. Res. 2002; 35: 984

23 Although List’s original paper reported a 97:3 er in the epoxidation step (see ref. 21), we could only partially reproduce this result, since the indirect er was 4:1, measured on compounds 21 and 22.
24 Ibuka T, Minakata H, Mitsui Y, Hayashi K, Taga T, Inbushi Y. Chem. Pharm. Bull. 1982; 30: 2840
25 Although compound 27 was reported by Ibuka, the spectroscopic data were not fully described. However, the key signals described for the title compound in ref. 24 matched with our data.
26 CCDC 1474251 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.

Supplementary Material

Supporting Information