Synthesis of (+)-Methyl Dihydropalustramate and of the Pyrido[1,2-a]azepine Core of Stemona Alkaloids

Camilla Mayer; Alexandra Romek; Thorsten Bach

doi:10.1055/s-0034-1380685

Synlett, Table of Contents

Synlett 2015; 26(11): 1505-1509
DOI: 10.1055/s-0034-1380685

letter

Synthesis of (+)-Methyl Dihydropalustramate and of the Pyrido[1,2-a]azepine Core of Stemona Alkaloids

Camilla Mayer

Department Chemie and Catalysis Research Center (CRC), Technische Universität München, 85747 Garching, Germany Email: thorsten.bach@ch.tum.de

,

Alexandra Romek

Department Chemie and Catalysis Research Center (CRC), Technische Universität München, 85747 Garching, Germany Email: thorsten.bach@ch.tum.de

,

Thorsten Bach*

Department Chemie and Catalysis Research Center (CRC), Technische Universität München, 85747 Garching, Germany Email: thorsten.bach@ch.tum.de

› Author Affiliations

Abstract

All articles of this category

Dedicated to Professor K. Peter C. Vollhardt

Abstract

Starting from a readily available, enantiomerically pure 2,6-disubstituted piperidine the synthesis of pyrido[1,2-a]azepines was accomplished. Key reactions for the ring closure were a photochemically induced acyl radical addition or a SmI₂-promoted ketyl radical addition to an α,β-unsaturated ester. En route to the cyclization precursor an epoxidiation/ring opening sequence led to an undesired oxazolidinone which turned out to be useful for the configuration assignment. The compound was successfully converted into (+)-methyl dihydropalustramate.

Key words

alkaloids - cyclization - piperidines - radical reaction - total synthesis

Full Text

References

References and Notes
1 For a review, see: Alibés R, Figueredo M. Eur. J. Org. Chem. 2009; 2421

For recently completed total syntheses, see:

2a Hoye AT, Wipf P. Org. Lett. 2011; 13: 2634
2b Honda T, Matsukawa T, Takahashi K. Org. Biomol. Chem. 2011; 9: 673
2c Chen Z, Chen Z, Zhang Y, Tu Y, Zhang F. J. Org. Chem. 2011; 76: 10173
2d Chen Z, Zhang Y, Chen Z, Tu Y, Zhang F. Chem. Commun. 2011; 47: 1836
2e Fujioka H, Nakahara K, Kotoku N, Ohba Y, Nagatomi Y, Wang T, Sawama Y, Murai K, Hirano K, Oki T, Wakamatsu S, Kita Y. Chem. Eur. J. 2012; 18: 13861
2f Bardaji N, Sánchez-Izquierdo N, Alibés R, Font J, Busqué F, Figueredo M. Org. Lett. 2012; 14: 4854
2g Swamy NK, Pyne SG. Heterocycles 2012; 84: 473
2h Schulte ML, Turlington ML, Phatak SS, Harp JM, Stauffer SR, Lindsley CW. Chem. Eur. J. 2013; 19: 11847
2i Kim C, Kang S, Rhee YH. J. Org. Chem. 2014; 79: 11119
2j Fu J, Shen H, Chang Y, Li C, Gong J, Yang Z. Chem. Eur. J. 2014; 20: 12881

For reviews, see:

3a Pyne SG, Ung AT, Jatisatienr A, Mungkornasawakul P. Mj. Int. J. Sci. Tech. 2007; 01: 157
3b Fischer G. Adv. Heterocycl. Chem. 2011; 103: 61

For recent reviews on Stemona alkaloids, see:

4a Pilli RA, Rosso GB, de Oliveira MC. F. Nat. Prod. Rep. 2010; 27: 1908
4b Greger H. Planta Med. 2006; 72: 99

5 Pilli RA, Rosso GB, de Oliveira MC. F. Alkaloids Chem. Biol. 2005; 62: 77

For examples, see:

6a Kaltenegger E, Brem B, Mereiter K, Kalchhauser H, Kählig H, Hofer O, Vajrodaya S, Greger H. Phytochemistry 2003; 63: 803
6b Mungkornasawakul P, Pyne SG, Jatisatienr A, Supyen D, Lie W, Ung AT, Skelton BW, White AH. J. Nat. Prod. 2003; 66: 980
6c Mungkornasawakul P, Pyne SG, Jatisatienr A, Supyen D, Jatisatienr C, Lie W, Ung AT, Skelton BW, White AH. J. Nat. Prod. 2004; 67: 675
6d Lin L.-G, Tang C.-P, Dien P.-H, Xu R.-S, Ye Y. Tetrahedron Lett. 2007; 48: 1559
6e Wang Y.-Z, Tang C.-P, Dien P.-H, Ye Y. J. Nat. Prod. 2007; 70: 1356

For previous synthetic studies, see:

7a Fozard A, Jones G. J. Org. Chem. 1965; 30: 1523
7b Tietze LF, Wünsch JR, Noltemeyer M. Tetrahedron 1992; 48: 2081
7c Marx K, Eberbach W. Tetrahedron 1997; 53: 14687
7d Chou S.-SP, Liang C.-F, Lee T.-M, Liu C.-F. Tetrahedron 2007; 63: 8267
7e De la Funeta MC, Dominguez D. J. Org. Chem. 2007; 72: 8804
7f Chaiyong S, Jatisatienr A, Mungkornasawakul P, Sastraruji T, Pyne SG, Ung AT, Urathamakul T, Lie W. J. Nat. Prod. 2010; 73: 1833
7g Shengule SR, Willis AC, Pyne SG. Tetrahedron 2013; 69: 8042

8a Chênevert R, Dickman M. J. Org. Chem. 1996; 61: 3332
8b Chênevert R, Ziarani GM, Morin MP, Dasser M. Tetrahedron: Asymmetry 1999; 10: 3117

9a Paulsen H, Todt K. Angew. Chem. Int. Ed. 1966; 5: 899
9b Sugg EE, Griffin JF, Portoghese PS. J. Org. Chem. 1985; 50: 5032

10a Toyooka N, Zhou D, Nemoto H, Tezuka Y, Kadota S, Jones TH, Garraffo HM, Spande TF, Daly JW. Synlett 2008; 1894
10b See also: Ookawa A, Soai K. J. Chem. Soc., Perkin Trans. 1 1987; 1465

11a Murray RW, Jeyaraman R. J. Org. Chem. 1985; 50: 2847
11b Murray RW, Singh M. Org. Synth. 1997; 74: 91
11c Bach RD, Dmitrenko O, Adam W, Schambony S. J. Am. Chem. Soc. 2003; 125: 924

12a Gilman H, Jones RG, Woods LA. J. Org. Chem. 1952; 17: 1630
12b Badorrey R, Porteña E, Diaz-de-Villegas MD, Galvez JA. Org. Biomol. Chem. 2009; 7: 2912

13a Omura K, Swern D. Tetrahedron 1978; 34: 1651
13b Lesma G, Colombo A, Landoni N, Sacchetti A, Silvani A. Tetrahedron: Asymmetry 2007; 18: 1948

14a Nader B, Bailey TR, Franck RW, Weinreb SM. J. Am. Chem. Soc. 1981; 103: 7573
14b Angle SR, Henry RM. J. Org. Chem. 1998; 63: 7490
14c Schützenmeister N, Müller M, Reinscheid UM, Griesinger C, Leonov A. Chem. Eur. J. 2013; 19: 17584

15a Seyferth D, Marmor RS, Hilbert P. J. Org. Chem. 1971; 36: 1379
15b Gilbert JC, Weerasooriya U. J. Org. Chem. 1979; 44: 4997
15c Maehr H, Schaffner C. Synth. Commun. 2009; 39: 299

16a Asao N, Ohishi T, Sato K, Yamamoto Y. J. Am. Chem. Soc. 2001; 123: 6931
16b Vintonyak VV, Maier ME. Org. Lett. 2007; 9: 655

17a Labonne A, Kribber T, Hintermann L. Org. Lett. 2006; 8: 5853
17b Boeck F, Kribber T, Xiao L, Hintermann L. J. Am. Chem. Soc. 2011; 133: 8138

18a Lindgren BO, Nilsson T. Acta Chem. Scand. 1973; 27: 888
18b Kraus GA, Roth B. J. Org. Chem. 1980; 45: 4825
18c Bal BS, Childers WE. Jr, Pinnick HW. Tetrahedron 1981; 2091

19a Muraoka O, Zheng B, Okumura K, Tanabe G, Momose T, Eugster CH. J. Chem. Soc., Perkin Trans. 1 1996; 1567
19b Mayer C, Trueb W, Wilson J, Eugster CH. Helv. Chim. Acta 1968; 51: 661

20 Behan JM, Johnstone RA. W, Wright MJ. J. Chem. Soc., Perkin. Trans. 1 1975; 1216

For reviews, see:

21a Tzirakis MD, Lykakis IN, Orfanopoulos M. Chem. Soc. Rev. 2009; 38: 2609
21b Tanielian C. Coord. Chem. Rev. 1998; 178-180: 1165
21c Hill CL. Synlett 1995; 127

22a Dondi D, Fagnoni M, Albini A. Chem. Eur. J. 2006; 12: 4153
22b Esposti S, Dondi D, Fagnoni M, Albini A. Angew. Chem. Int. Ed. 2007; 46: 2531

For reviews, see:

23a Nicolaou KC, Ellery SP, Chen JS. Angew. Chem. Int. Ed. 2009; 48: 7140
23b Edmonds DJ, Johnston D, Procter DJ. Chem. Rev. 2004; 104: 3371

Supplementary Material

Supporting Information

Primary Data

Primary Data