Tetrahydropyran Synthesis by
Intramolecular Conjugate Addition to Enones: Synthesis of the Clavosolide
Tetrahydropyran Ring

Roderick W. Bates; Ping Song

doi:10.1055/s-0030-1257890

PAPER

Tetrahydropyran Synthesis by Intramolecular Conjugate Addition to Enones: Synthesis of the Clavosolide Tetrahydropyran Ring

Roderick W. Bates, Ping Song
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371
Fax: +65 67911961; e-Mail: Roderick@ntu.edu.sg;

Abstract

All articles of this category

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

Full Text

References

<A NAME="RT03810SS-1A">1a</A> Fuwa H. Sasaki M. Org. Lett. 2010, 12: 584

<A NAME="RT03810SS-1B">1b</A> Takahashi S. Hongo Y. Tsukagoshi Y. Koshino H. Org. Lett. 2008, 10: 4223

<A NAME="RT03810SS-1C">1c</A> de Fïgueiredo RM. Fröhlich R. Christmann M. Angew. Chem. Int. Ed. 2007, 46: 2883

<A NAME="RT03810SS-1D">1d</A> Sommer S. Waldmann H. Chem. Commun. 2005, 5684

<A NAME="RT03810SS-1E">1e</A> Harvey JE. Raw SA. Taylor RJK. Org. Lett. 2004, 6: 2611

<A NAME="RT03810SS-1F">1f</A> Geisler LK. Nguyen S. Forsyth CJ. Org. Lett. 2004, 6: 4159

<A NAME="RT03810SS-1G">1g</A> Crimmins MT. Siliphaivanh P. Org. Lett. 2003, 5: 4641

<A NAME="RT03810SS-1H">1h</A> Hassfeld J. Christmann M. Kalesse M. Org. Lett. 2001, 3: 3561

<A NAME="RT03810SS-1I">1i</A> Masaki H. Maeyama J. Kamada K. Esumi T. Iwabuchi Y. Hatakeyama S. J. Am. Chem. Soc. 2000, 122: 5216

<A NAME="RT03810SS-1J">1j</A> Banwell MG. Bui CT. Phamb HTT. Simpson GW. J. Chem. Soc., Perkin Trans. 1 1996, 967

<A NAME="RT03810SS-1K">1k</A> 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:

<A NAME="RT03810SS-1L">1l</A> Nising CF. Bräse S. Chem. Soc. Rev. 2008, 37: 1218

For reviews of THP synthesis, see:

<A NAME="RT03810SS-1M">1m</A> Clarke PA. Santos S. Eur. J. Org. Chem. 2006, 2045

<A NAME="RT03810SS-1N">1n</A> Boivin TLB. Tetrahedron 1987, 43: 3309

<A NAME="RT03810SS-2A">2a</A> Yakushiji F. Maddaluno J. Yoshida M. Shishido K. Tetrahedron Lett. 2009, 50: 1504

<A NAME="RT03810SS-2B">2b</A> Bates RW. Song P. Tetrahedron 2007, 63: 4497

<A NAME="RT03810SS-2C">2c</A> Bressy C. Allais F. Cossy J. Synlett 2006, 3455

<A NAME="RT03810SS-3A">3a</A> Faulkner DJ. Nat. Prod. Rep. 2001, 18: 1

<A NAME="RT03810SS-3B">3b</A> Fu X. Schmitz FJ. Kelly-Borges M. McCready TL. Holmes CFB. J. Org. Chem. 1998, 63: 7957

<A NAME="RT03810SS-3C">3c</A> Rao MR. Faulkner DJ. J. Nat. Prod. 2002, 65: 386

<A NAME="RT03810SS-3D">3d</A> Erickson KL. Gustafson KR. Pannell LK. Beutler JA. Boyd MR. J. Nat. Prod. 2002, 65: 1303

For syntheses of clavosolides, see:

<A NAME="RT03810SS-4A">4a</A> Barry CS. Bushby N. Charmant JPH. Elsworth JD. Harding JR. Willis CL. Chem. Commun. 2005, 5097

<A NAME="RT03810SS-4B">4b</A> Lee HD. Kim NY. Kim SN. Son JB. Org. Lett. 2006, 8: 661

<A NAME="RT03810SS-4C">4c</A> Barry CS. Elsworth JD. Seden PT. Bushby N. Harding JR. Alder RW. Willis CL. Org. Lett. 2006, 8: 3319

<A NAME="RT03810SS-4D">4d</A> Smith AB. Simov V. Org. Lett. 2006, 8: 3315

<A NAME="RT03810SS-4E">4e</A> Lee HD. Kim NY. Kim SN. Son JB. Org. Lett. 2006, 8: 3411

<A NAME="RT03810SS-4F">4f</A> Chakraborty TK. Reddy VR. Chattopadhyay AK. Tetrahedron Lett. 2006, 47: 7435

<A NAME="RT03810SS-4G">4g</A> Yakambram P. Puranik VG. Gurjar MK. Tetrahedron Lett. 2006, 47: 3781

<A NAME="RT03810SS-4H">4h</A> Sedan PT. Charmant JPH. Willis CL. Org. Lett. 2008, 10: 1637

<A NAME="RT03810SS-5A">5a</A> Barry CS. Bushby N. Harding JR. Willis CL. Org. Lett. 2005, 7: 2683

<A NAME="RT03810SS-5B">5b</A> Blakemore PR. Browder CC. Hong J. Lincoln CM. Nagornyy PA. Robarge LA. Wardrop DJ. White JD. J. Org. Chem. 2005, 70: 5449

<A NAME="RT03810SS-6">6</A> Huckin SN. Weiler L. J. Am. Chem. Soc. 1974, 96: 1082

<A NAME="RT03810SS-7">7</A> Evans DA. Chapman KT. Carreira EM. J. Am. Chem. Soc. 1988, 110: 3560

<A NAME="RT03810SS-8">8</A> This anti-diol is an uncharacterised intermediate: Hassan A. Lu Y. Krische MJ. Org Lett. 2009, 11: 3112

<A NAME="RT03810SS-9">9</A> Chaterjee AK. Choi T.-L. Sanders DP. Grubbs RH. J. Am. Chem. Soc. 2003, 125: 11360

<A NAME="RT03810SS-10A">10a</A> 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:

<A NAME="RT03810SS-10B">10b</A> Loubinoux B. Sinnes J.-L. O’Sullivan AC. Winkler T. Tetrahedron 1995, 51: 3549

<A NAME="RT03810SS-10C">10c</A> Ali SM. Georg GI. Tetrahedron Lett. 1997, 38: 1703

<A NAME="RT03810SS-10D">10d</A> Eggar M. Mossman CJ. Buck SB. Nair SK. Bhat L. Ali SM. Reiff SA. Boge TC. Georg GI. J. Org. Chem. 2000, 65: 7992

<A NAME="RT03810SS-11A">11a</A> Brown HC. Bhat KS. J. Am. Chem. Soc. 1986, 108: 293

<A NAME="RT03810SS-11B">11b</A> Brown HC. Bhat KS. J. Am. Chem. Soc. 1986, 108: 5919

<A NAME="RT03810SS-11C">11c</A> Kim Y.-J. Wang P. Navarro-Villalobos M. Rhode BD. DerryBerry J. Gin DY. J. Am. Chem. Soc. 2006, 128: 11906

<A NAME="RT03810SS-12">12</A> Song SH. Grubbs RH. J. Am. Chem. Soc. 2006, 128: 3508

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.

<A NAME="RT03810SS-14">14</A> Tietze LF. Eicher T. Reactions and Syntheses in the Organic Chemistry Laboratory University Science Books; Mill Valley California: 1989. p.117

<A NAME="RT03810SS-15A">15a</A> Lu K. Huang MW. Xiang Z. Liu YX. Chen JH. Yang Z. Org. Lett. 2006, 8: 1193

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.

<A NAME="RT03810SS-16">16</A> Mori I. Ishihara K. Heathcock CH. J. Org. Chem. 1990, 55: 1114

The enantiomer was prepared by White et al. (ref. 5b).