Direct, Biomimetic Synthesis of (+)-Artemone via a Stereoselective, Organocatalytic Cyclization

Abstract

We present a four-step synthesis of (+)-artemone from (–)-linalool, featuring iminium organocatalysis of a doubly diastereoselective conjugate addition reaction. The strategy follows a proposed biosynthetic pathway, rapidly generates stereochemical complexity, uses no protecting groups, and minimizes redox manipulations.

Key words

natural products - cyclization - terpenoids - total synthesis - stereoselective synthesis - green chemistry - organocatalysis - biomimetic synthesis

• References

• 1a Naegeli P, Klimes J, Weber G. Tetrahedron Lett. 1970; 5021
• 1b Misra LN, Chandra A, Thakur RS. Phytochemistry 1991; 30: 549
• 2a Vajs V, Trifunovic S, Janackovic P, Sokovic M, Milosavljevic S, Tesevic V. J. Serb. Chem. Soc. 2004; 69: 969
• 2b Perfumi M, Paparelli F, Cingolani ML. J. Essent. Oil Res. 1995; 7: 387
• 2c Schmidt E, Bail S, Friedl SM, Jirovetz L, Buchbauer G, Wanner J, Denkova Z, Slavchev A, Stoyanova A, Geissler M. Nat. Prod. Commun. 2010; 5: 1365
• 3 Siska P, Fodran P, Szolcsanyi P. Tetrahedron 2014; 70: 6420
• 4 Honda Y, Ori A, Tsuchihashi G. Chem. Lett. 1987; 1259
• 5 Wan KK, Evans-Klock CD, Fielder BC, Vosburg DA. Synthesis 2013; 45: 1541
• 6a Akhila A, Sharma PK, Thakur RS. Tetrahedron Lett. 1986; 27: 5885
• 6b Thakur RS, Akhila A In Newer Trends in Essential Oils and Flavours: Selected Papers Presented at the International Symposium . Dhar KL, Thappa RK, Agarwal SG. Tata McGraw-Hill; New Delhi: 1993: 51
• 7 Morrison KC, Litz JP, Scherpelz KP, Dossa PD, Vosburg DA. Org. Lett. 2009; 11: 2217
• 8 Naegeli P, Weber G. Tetrahedron Lett. 1970; 959
• 9 Gaich T, Baran PS. J. Org. Chem. 2010; 75: 4657
• 10 Sharma ML, Chand T. Proc. Indian Acad. Sci. (Chem. Sci.) 1996; 108: 21
• 11 Melchiorre P. Angew. Chem. Int. Ed. 2012; 51: 9748
• 12a Marigo M, Wabnitz TC, Fielenbach D, Jørgensen KA. Angew. Chem. Int. Ed. 2005; 44: 794
• 12b Hayashi Y, Gotoh H, Hayashi T, Shoji M. Angew. Chem. Int. Ed. 2005; 44: 4212
• 12c Ishikawa H, Suzuki T, Hayashi Y. Angew. Chem. Int. Ed. 2009; 48: 1304
• 12d Ishikawa H, Honma M, Hayashi Y. Angew. Chem. Int. Ed. 2011; 50: 2824
• 13 Fleury LM, Ashfeld BL. Org. Lett. 2009; 11: 5670
• 14a Richter JM, Ishihara Y, Masuda T, Whitefield BW, Llamas T, Pohjakallio A, Baran PS. J. Am. Chem. Soc. 2008; 130: 17938
• 14b Burns NZ, Baran PS, Hoffmann RW. Angew. Chem. Int. Ed. 2009; 48: 2854
• 15 Sabitha G, Prasad MN, Bhikshapathi M, Yadav JS. Synthesis 2010; 807