Synthesis of cis- and trans-Davanoids: Artemone, Hydroxydavanone, Isodavanone, and Nordavanone

This paper is dedicated to Prof. Christopher T. Walsh on the occasion of his retirement in 2013.

Abstract

A concise and versatile synthesis of both cis and trans dia­stereomers of the natural products artemone, hydroxydavanone, isodavanone, and nordavanone has been accomplished. The preparation of trans-davanone is also described. Each synthesis is six to eight steps from geranyl acetate, with differentiation between cis and trans products occurring through a diastereoselective cyclization prior to derivatization. Many of these compounds are minor components of davana oil and have now been synthesized for the first time.

Key words

davanone - terpenoids - total synthesis - stereoselective synthesis - green chemistry - asymmetric allylic O-alkylation

• References

• 1 Misra LN, Chandra A, Thakur RS. Phytochemistry 1991; 30: 549
• 2 Sipma G, van der Waal B. Rec. Trav. Chim. Pays-Bas 1968; 87: 715
• 3 Vajs V, Trifunovic S, Janackovic P, Sokovic M, Milosavljevic S, Tesevic V. J. Serb. Chem. Soc. 2004; 69: 969
• 4 Perfumi M, Paparelli F, Cingolani ML. J. Essent. Oil Res. 1995; 7: 387
• 5 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
• 6a Naegeli P, Weber G. Tetrahedron Lett. 1970; 959
• 6b Ohloff G, Giersch W. Helv. Chim. Acta 1970; 53: 841
• 6c Birch AJ, Corrie JE. T, Subba Rao GS. R. Aust. J. Chem. 1970; 23: 1811
• 6d Bartlett PA, Holmes CP. Tetrahedron Lett. 1983; 24: 1365
• 6e Honda Y, Ori A, Tsuchihashi G. Chem. Lett. 1987; 1259
• 6f Molander GA, Haas J. Tetrahedron 1999; 55: 617
• 6g Morrison KC, Litz JP, Scherpelz KP, Dossa PD, Vosburg DA. Org. Lett. 2009; 11: 2217
• 6h Sabitha G, Prasad MN, Bhikshapathi M, Yadav JS. Synthesis 2010; 807
• 7a Baran PS, Shenvi RA, Mitsos CA. Angew. Chem. Int. Ed. 2005; 44: 3714

In our case and in Baran’s, neighboring Lewis basic groups may stabilize the tetrahedral intermediate and prevent a second Grignard addition. Double prenylation (likely γ and then α) of esters has been observed for simpler esters:
• 7b Inaba T, Aoki H, Watanabe S, Sakamoto M, Fujita T. J. Chem. Tech. Biotechnol. 1991; 52: 407 . It is possible that α-prenylation is preferred for steric reasons on congested carbonyls, as in Inaba’s presumed γ-prenyl ketone intermediates and our Weinreb amide 6. Molander also observed α-prenylation of a Weinreb amide with a Grignard reagent; see ref. 6f
• 8 Naegeli P, Klimes J, Weber G. Tetrahedron Lett. 1970; 5021
• 9 Thomas AF, Ozainne M. Helv. Chim. Acta 1974; 57: 2062
• 10 For nonstereoselective syntheses of all davanone stereoisomers, see references 6a–c.
• 11 Patterson I, Yeung K.-S, Smaill JB. Synlett 1993; 774
• 12 Denmark SE, Stavenger RA. J. Am. Chem. Soc. 2000; 122: 8837
• 13 Shorter reaction times left the silyl protecting group intact.
• 14 All compounds have an 8:1 er derived from an initial Sharpless asymmetric epoxidation; see ref. 6g.
• 15a Richter JM, Ishihara Y, Masuda T, Whitefield BW, Llamas T, Pohjakallio A, Baran PS. J. Am. Chem. Soc. 2008; 130: 17938
• 15b Burns NZ, Baran PS, Hoffmann RW. Angew. Chem. Int. Ed. 2009; 48: 2854
• 16 Wan, K. K.; Maloney, K. N., unpublished results.
• 17 Bidan G, Kossanyi J, Meyer V, Morizur J.-P. Tetrahedron 1977; 2193