Synthetic Studies Towards Spirocyclic Imine Marine Toxins Using N-Acyl Iminium Ions as Dienophiles in Diels–Alder Reactions

Abstract

Cyclic imine marine toxins have attracted considerable attention from the synthetic community in the past two decades due to their unique chemical structures and clinically relevant biological activities. This review presents recent efforts of our group in the development of various strategies to efficiently construct the common spirocyclic imine fragments of the cyclic imine toxins. In particular, the use of α,β-unsaturated N-acyl iminium ion dienophiles in Diels–Alder reactions are highlighted, whereby direct access to spirocyclic imine motifs was obtained and important mechanistic details were discovered. Alternative approaches to spirocyclic imine systems involving hydroamination of amino alkynes are also summarized. One such approach led to serendipitous access to N-vinyl amide products, while our most recently ­reported approach involving an intermolecular Diels–Alder/cross-­coupling sequence using novel 2-bromo-1,3-butadienes to access 5,6-spirocyclic imines is also discussed. Additionally, the development of a novel method to construct another challenging motif present in the portimines is also introduced.

1 Introduction

2 Strategies towards the Spirocyclic Imine Fragment of Cyclic Imine Toxins

2.1 Diels–Alder Cycloadditions of α,β-Unsaturated N-Acyl Iminium Dienophiles

2.2 Early Studies Using in situ-Generated Iminium Ion Dienophiles

2.3 Use of More Stable Iminium Ion Dienophiles for Diels–Alder Reactions

2.4 Other Notable Strategies towards Spirocyclic Imines

2.5 Recent Efforts towards the 5,6-Spirocyclic Imine Marine Toxin Portimine A

2.6 Construction of Another Challenging Motif of Portimine A

3 Conclusion and Future Perspectives

Key words

spiroimines - Diels-Alder reaction - N-acyl iminium ions - Mukaiyama Michael addition - iminium dienophiles

• References

• 1 Brand LE, Campbell L, Bresnan E. Harmful Algae 2012; 14: 156
• 2 Grattan LM, Holobaugh S, Morris JG. Harmful Algae 2016; 57: 2
• 3 Hermawan I, Higa M, Hutabarat PU. B, Fujiwara T, Akiyama K, Kanamoto A, Haruyama T, Kobayashi N, Higashi M, Suda S. Mar. Drugs 2019; 17: 35
• 4 Guéret SM, Brimble MA. Nat. Prod. Rep. 2010; 27: 1350
• 5 Otero A, Chapela M.-J, Atanassova M, Vieites JM, Cabado AG. Chem. Res. Toxicol. 2011; 24: 1817
• 6 Molgó J, Marchot P, Aráoz R, Benoit E, Iorga BI, Zakarian A, Taylor P, Bourne Y, Servent D. J. Neurochem. 2017; 142: 41
• 7 Uemura D, Chou T, Haino T, Nagatsu A, Fukuzawa S, Zheng S, Chen H. J. Am. Chem. Soc. 1995; 117: 1155
• 8 McCauley JA, Nagasawa K, Lander PA, Mischke SG, Semones MA, Kishi Y. J. Am. Chem. Soc. 1998; 120: 7647
• 9 Takada N, Umemura N, Suenaga K, Chou T, Nagatsu A, Haino T, Yamada K, Uemura D. Tetrahedron Lett. 2001; 42: 3491
• 10 Otero P, Alfonso A, Rodríguez P, Rubiolo JA, Cifuentes J, Bermúdez R, Vieytes MR, Botana LM. Food Chem. Toxicol. 2012; 50: 232
• 11 Bourne Y, Radic Z, Aráoz R, Talley TT, Benoit E, Servent D, Taylor P, Molgó J, Marchot P. Proc. Natl. Acad. Sci. U.S.A. 2010; 107: 6076
• 12 Selwood AI, Wilkins AL, Munday R, Shi F, Rhodes LL, Holland PT. Tetrahedron Lett. 2013; 54: 4705
• 13 Cuddihy SL, Drake S, Harwood DT, Selwood AI, McNabb PS, Hampton MB. Apoptosis 2016; 21: 1447
• 14 Hu T, Curtis JM, Walter JA, Wright JL. C. Tetrahedron Lett. 1996; 37: 7671
• 15 Stewart M, Blunt JW, Munro MH, Robinson WT, Hannah DJ. Tetrahedron Lett. 1997; 38: 4889
• 16 Ahn Y, Cardenas GI, Yang J, Romo D. Org. Lett. 2001; 3: 751
• 17 O’Connor PD, Brimble MA. Nat. Prod. Rep. 2007; 24: 869
• 18 Stivala CE, Benoit E, Aráoz R, Servent D, Novikov A, Molgó J, Zakarian A. Nat. Prod. Rep. 2015; 32: 411
• 19 Tsuchikawa H, Minamino K, Hayashi S, Murata M. Asian J. Org. Chem. 2017; 6: 1322
• 20 Hatakeyama S, Ishihara J, Tojo S, Makino T, Sekiya H, Tanabe A, Shiraishi M, Murai A. Heterocycles 2017; 95: 422
• 21 Saito T, Fujiwara K, Kondo Y, Akiba U, Suzuki T. Tetrahedron Lett. 2019; 60: 386
• 22 Guthertz A, Lusseau J, Desvergnes V, Massip S, Landais Y. Chem. Eur. J. 2019; 25: 1553
• 23 Ishihara J, Usui F, Kurose T, Baba T, Kawaguchi Y, Watanabe Y, Hatakeyama S. Chem. Eur. J. 2019; 25: 1543
• 24 Guéret SM, Brimble MA. Pure Appl. Chem. 2011; 83: 425
• 25 Brimble MA, Crimmins D, Trzoss M. ARKIVOC 2005; (i): 39
• 26 Guéret SM, Furkert DP, Brimble MA. Org. Lett. 2010; 12: 5226
• 27 Trzoss M, Brimble MA. Synlett 2003; 2042
• 28 Brimble MA, Trzoss M. Tetrahedron 2004; 60: 5613
• 29 Crimmins D, Dimitrov I, O’Connor PD, Caprio V, Brimble MA. Synthesis 2008; 3319
• 30 Guéret SM, O’Connor PD, Brimble MA. Org. Lett. 2009; 11: 963
• 31 MacKinnon SL, Cembella AD, Burton IW, Lewis N, LeBlanc P, Walter JA. J. Org. Chem. 2006; 71: 8724
• 32 Kong K, Moussa Z, Lee C, Romo D. J. Am. Chem. Soc. 2011; 133: 19844
• 33 Ishihara J, Horie M, Shimada Y, Tojo S, Murai A. Synlett 2002; 403
• 34 Nakamura S, Kikuchi F, Hashimoto S. Angew. Chem. Int. Ed. 2008; 47: 7091
• 35 White JD, Wang G, Quaranta L. Org. Lett. 2003; 5: 4983
• 36 White JD, Quaranta L, Wang G. J. Org. Chem. 2007; 72: 1717
• 37 Johannes JW, Wenglowsky S, Kishi Y. Org. Lett. 2005; 7: 3997
• 38 Zou Y, Che Q, Snider BB. Org. Lett. 2006; 8: 5605
• 39 Kim J, Thomson RJ. Angew. Chem. Int. Ed. 2007; 46: 3104
• 40 O’Connor PD, Körber K, Brimble MA. Synlett 2008; 1036
• 41 O’Connor PD, Marino M, Guéret SM, Brimble MA. J. Org. Chem. 2009; 74: 8893
• 42 Roush WR, Brown BB. J. Org. Chem. 1992; 57: 3380
• 43 Berson JA, Hamlet Z, Mueller WA. J. Am. Chem. Soc. 1962; 84: 297
• 44 Marcoux D, Bindschädler P, Speed AW. H, Chiu A, Pero JE, Borg GA, Evans DA. Org. Lett. 2011; 13: 3758
• 45 Brimble MA, Gorsuch S. Aust. J. Chem. 1999; 52: 965
• 46 Wang Z, Krogsgaard-Larsen N, Daniels B, Furkert DP, Brimble MA. J. Org. Chem. 2016; 81: 10366
• 47 Freeman JL, Brimble MA, Furkert DP. Org. Biomol. Chem. 2019; 17: 2705
• 48 Yang J, Cohn ST, Romo D. Org. Lett. 2000; 2: 763
• 49 Yazici A, Pyne SG. Synthesis 2009; 513
• 50 Wu P, Nielsen TE. Chem. Rev. 2017; 117: 7811
• 51 Duroure L, Jousseaume T, Aráoz R, Barré E, Retailleau P, Chabaud L, Molgó J, Guillou C. Org. Biomol. Chem. 2011; 9: 8112
• 52 Pelc MJ, Zakarian A. Org. Lett. 2005; 7: 1629
• 53 Rambla M, Duroure L, Chabaud L, Guillou C. Eur. J. Org. Chem. 2014; 7716
• 54 Zhang YC, Furkert DP, Guéret SM, Lombard F, Brimble MA. Tetrahedron Lett. 2011; 52: 4896
• 55 Unsworth WP, Gallagher KA, Jean M, Schmidt JP, Diorazio LJ, Taylor RJ. K. Org. Lett. 2013; 15: 262
• 56 Choi H, Shirley HJ, Hume PA, Brimble MA, Furkert DP. Angew. Chem. Int. Ed. 2017; 56: 7420
• 57 Fribley AM, Xi Y, Makris C, Alves-de-Souza C, York R, Tomas C, Wright JL. C, Strangman WK. ACS Med. Chem. Lett. 2019; 10: 175
• 58 Choi H, Shirley HJ, Aitken HR. M, Schulte T, Söhnel T, Hume PA, Brimble MA, Furkert DP. Org. Lett. 2020; in press; doi:
• 59 Ding X.-B, Furkert DP, Brimble MA. Angew. Chem. Int. Ed. 2019; 58: 11830