Total Synthesis of (+)-Cavicularin: The Pyrone Diels–Alder Reaction in Enantioselective Cyclophane Synthesis

We dedicate this paper to Prof. Kenneth W. Hedberg on the occasion of his 95^th birthday.

Abstract

A pyrone Diels–Alder strategy was developed for the synthesis of the cyclophane natural product, cavicularin. The strategy uses a vinyl sulfone as an alkyne equivalent dienophile. An enantioselective variant delivered (+)-cavicularin.

Key words

Diels–Alder - pyrone - cyclophane - chirality - total synthesis

• References and Notes

• 1a Salih MQ, Beaudry CM. Org. Lett. 2013; 15: 4540
• 1b Salih MQ, Beaudry CM. Org. Lett. 2012; 14: 4026
• 1c Salih MQ, Beaudry CM. Org. Lett. 2014; 16: 4964
• 1d Zhu Z.-Q, Beaudry CM. J. Org. Chem. 2013; 78: 3336
• 1e Zhu Z.-Q, Salih MQ, Fynn E, Bain AD, Beaudry CM. J. Org. Chem. 2013; 78: 2881
• 2a Keserű GM, Nógrádi M. Nat. Prod. Rep. 1995; 12: 69
• 2b Asakawa Y, Toyota M, Hashimoto T, Tori M, Nagashima F, Harinantenaina L. Heterocycles 2008; 76: 99
• 3 Toyota M, Yoshida T, Kan Y, Takaoka S, Asakawa Y. Tetrahedron Lett. 1996; 37: 4745
• 4a Zhao P, Beaudry CM. Org. Lett. 2013; 15: 402
• 4b Zhao P, Beaudry CM. Angew. Chem. Int. Ed. 2014; 53: 10500
• 5a Harrowven DC, Woodcock T, Howes PD. Angew. Chem. Int. Ed. 2005; 44: 3899
• 5b Dam JH. Dissertation 2009
• 5c Harada K, Makino K, Shima N, Okuyama H, Esumi T, Kubo M, Hioki H, Asakawa Y, Fukuyama Y. Tetrahedron 2013; 69: 6959
• 6 Takiguchi H, Ohmori K, Suzuki K. Angew. Chem. Int. Ed. 2013; 52: 10472
• 7a Baran PS, Burns NZ. J. Am. Chem. Soc. 2006; 128: 3908
• 7b Gulder T, Baran PS. Nat. Prod. Rep. 2012; 29: 899

For reviews, see:
• 8a Woodard BT, Posner GH. Advances in Cycloaddition . Vol. 5. Harmata M. JAI Press; Connecticut: 1999: 47
• 8b Afarinkia K, Vinader V, Nelson TD, Posner GH. Tetrahedron 1992; 48: 9111
• 9a Pindur U, Erfanian-Abdoust H. Liebigs Ann. Chem. 1989; 12: 1275
• 9b Pratt AJ, Rendle PM, Steel PJ. Aust. J. Chem. 2011; 64: 945
• 10a Okamura H, Nakamura Y, Iwagawa T, Nakatani M. Chem. Lett. 1996; 193
• 10b Wang Y, Li H, Wang Y.-Q, Liu Y, Foxman BM, Deng L. J. Am. Chem. Soc. 2007; 129: 6364
• 10c Singh RP, Bartelson K, Wang Y, Su H, Lu X, Deng L. J. Am. Chem. Soc. 2008; 130: 2422
• 11 Soh JY.-T, Tan C.-H. J. Am. Chem. Soc. 2009; 131: 6904
• 12a Posner GH, Dai H, Bull DS, Lee J.-K, Eydoux F, Ishihara Y, Welsh W, Pryor N, Petr S. J. Org. Chem. 1996; 61: 671
• 12b Posner GH, Eydoux F, Lee JK, Bull DS. Tetrahedron Lett. 1994; 35: 7541
• 12c Markó IE, Chellé-Regnaut I, Leroy B, Warriner SL. Tetrahedron Lett. 1997; 38: 4269
• 12d Markó IE, Evans GR, Seres P, Chelle I, Janousek Z. Pure Appl. Chem. 1996; 68: 113
• 13 Wu W, Min L, Zhu L, Lee C.-S. Adv. Synth. Catal. 2011; 353: 1135
• 14 See ref. 4b for preparation.

Alkenes are well known to slow the rate of oxidative additions, see:
• 15a Johnson JB, Rovis T. Angew. Chem. Int. Ed. 2008; 47: 840
• 15b Amatore C, Jutand A, Khalil F, M’Barki MA, Mottier L. Organometallics 1993; 12: 3168
• 15c Amatore C, Broeker G, Jutand A, Khalil F. J. Am. Chem. Soc. 1997; 119: 5176
• 16a Schröter S, Stock C, Bach T. Tetrahedron 2005; 61: 2245
• 16b Schnürch M, Flasik R, Khan AF, Spina M, Mihovilovic MD, Stanetty P. Eur. J. Org. Chem. 2006; 3283
• 16c Schröter S, Bach T. Synlett 2005; 1957
• 16d Handy ST, Sabatini JJ. Org. Lett. 2006; 8: 1537
• 17a Ullah I, Nawaz M, Villinger A, Langer P. Synlett 2011; 1895
• 17b Sharif M, Zeeshan M, Reimann S, Villinger A, Langer P. Tetrahedron Lett. 2010; 51: 2810
• 17c Manabe K, Yamaguchi M. Catalysts 2014; 4: 307
• 17d Houpis IN, Huang C, Nettekoven U, Chen JG, Liu R, Canters M. Org. Lett. 2008; 10: 5601
• 17e Sharif M, Maalik A, Reimann S, Feist H, Iqbal J, Patonay T, Villinger A, Langer P. J. Fluorine Chem. 2013; 146: 19
• 17f Ali I, Siyo B, Hassan Z, Malik I, Ullah I, Ali A, Nawaz M, Iqbal J, Patonay T, Villinger A, Langer P. J. Fluorine Chem. 2013; 145: 18
• 18 Zhao P, Young MD, Beaudry CM. Org. Biomol. Chem. 2015; 13: 6162
• 19 Unpublished results.