RSS-Feed abonnieren
DOI: 10.1055/s-0030-1257890
Tetrahydropyran Synthesis by Intramolecular Conjugate Addition to Enones: Synthesis of the Clavosolide Tetrahydropyran Ring
Publikationsverlauf
Publikationsdatum:
22. Juli 2010 (online)
![](https://www.thieme-connect.de/media/synthesis/201017/lookinside/thumbnails/10.1055-s-0030-1257890-1.jpg)
Abstract
The synthesis of a tetrahydropyran intermediate for clavosolide A is reported, employing a combination of cross-metathesis and intramolecular oxa-Michael addition. The intramolecular oxa-Michael addition to α,β-unsaturated esters requires the use of strong bases and can result in either modest yields or stereoisomeric mixtures, and can be highly variable according to the substrate structure. In contrast, the corresponding ketones cyclise under very mild conditions to give the 2,6-cis-isomers directly. The use of appropriately substituted ketones allows efficient conversion into esters.
Key words
Michael addition - tandem reaction - cyclisation
-
1a
Fuwa H.Sasaki M. Org. Lett. 2010, 12: 584 -
1b
Takahashi S.Hongo Y.Tsukagoshi Y.Koshino H. Org. Lett. 2008, 10: 4223 -
1c
de Fïgueiredo RM.Fröhlich R.Christmann M. Angew. Chem. Int. Ed. 2007, 46: 2883 -
1d
Sommer S.Waldmann H. Chem. Commun. 2005, 5684 -
1e
Harvey JE.Raw SA.Taylor RJK. Org. Lett. 2004, 6: 2611 -
1f
Geisler LK.Nguyen S.Forsyth CJ. Org. Lett. 2004, 6: 4159 -
1g
Crimmins MT.Siliphaivanh P. Org. Lett. 2003, 5: 4641 -
1h
Hassfeld J.Christmann M.Kalesse M. Org. Lett. 2001, 3: 3561 -
1i
Masaki H.Maeyama J.Kamada K.Esumi T.Iwabuchi Y.Hatakeyama S. J. Am. Chem. Soc. 2000, 122: 5216 -
1j
Banwell MG.Bui CT.Phamb HTT.Simpson GW. J. Chem. Soc., Perkin Trans. 1 1996, 967 -
1k
Nicolaou KC.Theodorakis EA.Rutjes FPJT.Tiebes J.Sato M.Untersteller E.Xiao X.-Y. J. Am. Chem. Soc. 1995, 117: 1171 - For a review, see:
-
1l
Nising CF.Bräse S. Chem. Soc. Rev. 2008, 37: 1218 - For reviews of THP synthesis, see:
-
1m
Clarke PA.Santos S. Eur. J. Org. Chem. 2006, 2045 -
1n
Boivin TLB. Tetrahedron 1987, 43: 3309 -
2a
Yakushiji F.Maddaluno J.Yoshida M.Shishido K. Tetrahedron Lett. 2009, 50: 1504 -
2b
Bates RW.Song P. Tetrahedron 2007, 63: 4497 -
2c
Bressy C.Allais F.Cossy J. Synlett 2006, 3455 -
3a
Faulkner DJ. Nat. Prod. Rep. 2001, 18: 1 -
3b
Fu X.Schmitz FJ.Kelly-Borges M.McCready TL.Holmes CFB. J. Org. Chem. 1998, 63: 7957 -
3c
Rao MR.Faulkner DJ. J. Nat. Prod. 2002, 65: 386 -
3d
Erickson KL.Gustafson KR.Pannell LK.Beutler JA.Boyd MR. J. Nat. Prod. 2002, 65: 1303 - For syntheses of clavosolides, see:
-
4a
Barry CS.Bushby N.Charmant JPH.Elsworth JD.Harding JR.Willis CL. Chem. Commun. 2005, 5097 -
4b
Lee HD.Kim NY.Kim SN.Son JB. Org. Lett. 2006, 8: 661 -
4c
Barry CS.Elsworth JD.Seden PT.Bushby N.Harding JR.Alder RW.Willis CL. Org. Lett. 2006, 8: 3319 -
4d
Smith AB.Simov V. Org. Lett. 2006, 8: 3315 -
4e
Lee HD.Kim NY.Kim SN.Son JB. Org. Lett. 2006, 8: 3411 -
4f
Chakraborty TK.Reddy VR.Chattopadhyay AK. Tetrahedron Lett. 2006, 47: 7435 -
4g
Yakambram P.Puranik VG.Gurjar MK. Tetrahedron Lett. 2006, 47: 3781 -
4h
Sedan PT.Charmant JPH.Willis CL. Org. Lett. 2008, 10: 1637 -
5a
Barry CS.Bushby N.Harding JR.Willis CL. Org. Lett. 2005, 7: 2683 -
5b
Blakemore PR.Browder CC.Hong J.Lincoln CM.Nagornyy PA.Robarge LA.Wardrop DJ.White JD. J. Org. Chem. 2005, 70: 5449 - 6
Huckin SN.Weiler L. J. Am. Chem. Soc. 1974, 96: 1082 - 7
Evans DA.Chapman KT.Carreira EM. J. Am. Chem. Soc. 1988, 110: 3560 - 8 This anti-diol
is an uncharacterised intermediate:
Hassan A.Lu Y.Krische MJ. Org Lett. 2009, 11: 3112 - 9
Chaterjee AK.Choi T.-L.Sanders DP.Grubbs RH. J. Am. Chem. Soc. 2003, 125: 11360 -
10a
Genêt JP.Ratovelomanana-Vidal V.Caño de Andrade MC.Pfister X.Guerreiro P.Lenoir JY. Tetrahedron Lett. 1995, 36: 4801 - For other reports of the asymmetric reduction of β-keto ester 3, see:
-
10b
Loubinoux B.Sinnes J.-L.O’Sullivan AC.Winkler T. Tetrahedron 1995, 51: 3549 -
10c
Ali SM.Georg GI. Tetrahedron Lett. 1997, 38: 1703 -
10d
Eggar M.Mossman CJ.Buck SB.Nair SK.Bhat L.Ali SM.Reiff SA.Boge TC.Georg GI. J. Org. Chem. 2000, 65: 7992 -
11a
Brown HC.Bhat KS. J. Am. Chem. Soc. 1986, 108: 293 -
11b
Brown HC.Bhat KS. J. Am. Chem. Soc. 1986, 108: 5919 -
11c
Kim Y.-J.Wang P.Navarro-Villalobos M.Rhode BD.DerryBerry J.Gin DY. J. Am. Chem. Soc. 2006, 128: 11906 - 12
Song SH.Grubbs RH. J. Am. Chem. Soc. 2006, 128: 3508 - 14
Tietze LF.Eicher T. Reactions and Syntheses in the Organic Chemistry Laboratory University Science Books; Mill Valley California: 1989. p.117 -
15a
Lu K.Huang MW.Xiang Z.Liu YX.Chen JH.Yang Z. Org. Lett. 2006, 8: 1193 -
15b
In our case, the alcohol was prepared by the addition of vinylmagnesium chloride to (tert-butyldimethylsilyloxy)acetaldehyde, which in turn was prepared by ozonolysis of the bis-TBS ether of cis-but-2-ene-1,4-diol.
- 16
Mori I.Ishihara K.Heathcock CH. J. Org. Chem. 1990, 55: 1114
References
Data for the trans-isomer of tetrahydropyran 2: [α]D ²5 +90.6 (c 0.28, CH2Cl2). IR (neat): 3054, 2952, 2926, 2855, 1714, 1434, 1315, 1200, 1177, 1098, 898 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 0.99 (3 H, d, J = 6.9 Hz), 1.20-1.32 (2 H, m), 1.47 (1 H, d, J = 3.0 Hz), 1.75-1.91 (2 H, m), 1.99 (1 H, ddd, J = 12.5, 4.3, 2.6 Hz), 2.44 (1 H, dd, J = 14.5, 4.4 Hz), 2.65 (1 H, dd, J = 14.5, 11.0 Hz), 3.48-3.62 (3 H, m), 3.66 (3 H, s), 3.85-3.89 (1 H, m), 4.43 (1 H, ddd, J = 10.8, 5.1, 4.9 Hz), 4.48 (1 H, d, J = 11.8 Hz), 4.54 (1 H, d, J = 11.8 Hz), 7.26-7.36 (5 H, m). ¹³C NMR (75 MHz, CDCl3): δ = 172.0, 138.5, 128.4, 127.7, 127.5, 73.9, 73.1, 69.7, 66.9, 66.7, 51.7, 41.0, 40.4, 36.0, 33.4, 13.1. MS (EI): m/z = 345 (M + Na), 323 (M + H), 214. HRMS (EI): m/z calcd for C18H27O5 (M + H): 323.1858; found: 323.1859.
17The enantiomer was prepared by White et al. (ref. 5b).