Download PDF
Synthesis 2001(16): 2401-2414
DOI: 10.1055/s-2001-18717
PAPER
© Georg Thieme Verlag Stuttgart · New York

2-Acetonyl-2,4-di(hydroxy)tetrahydropyrans versus γ-Pyrones: A Chemodivergent Issue for the Condensation of Acetylacetone Dianion Equivalents with α,β-Disubstituted β-Hydroxyaldehydes Leading to Potential New Synthons for Spiroketals

Vivien Henryon, Lu Wei Liu, Roman Lopez, Joëlle Prunet, Jean-Pierre Férézou*
Laboratoire de Syntèse Organique associé au C.N.R.S., DCSO, Ecole Polytechnique, 91128 Palaiseau, France
e-Mail: bitnet.ferezou@polytechnique.fr;
Further Information

Publication History

Received 23 July 2001
Publication Date:
05 August 2004 (online)

    Permissions and Reprints All articles of this category

Abstract

In order to develop a new route to ketal or spiroketal subunits present in numerous natural products, condensation of acetylacetone bis(silyl)enol ether 2-Si or acetylacetone lithium dianion 2-Li with various anti α,β-disubstituted β-hydroxy aldehydes 11 was studied. It has been shown that under Lewis acid-promoted Mukaiyama conditions it is possible to realize such condensation reactions without formation of the well-known Danishefsky γ-pyrones 8. The required 2-acetonyl-2,4-dihydroxytetrahydropyrans 1 for further synthetic purposes were prepared in good to high yields from the intermediate acyclic aldol adduct 7. Particularly crucial are i) the deprotection conditions of the O-silyl protected acyclic intermediate 7 with tetrabutylammonium fluoride in dimethylformamide, and ii) the subsequent montmorillonite K10-promoted protection of the hemiketal 1 hydroxy group. The parameters governing the stereoselectivity of the initial condensation reaction have been studied. Under apparent Felkin or anti-Felkin/Cram-chelate conditions, syn,anti-adducts are obtained with high selectivity from acetylacetone bis(silyl) enol ether 2-Si. Partial modulation of the stereoselectivity can be achieved through condensation of the acetylacetone lithium dianion 2-Li with aldehydes bearing bulky O-silyl protecting groups which allows a preferential access to the anti,anti triads.

Key words

silyl enols ethers - dianions - aldol reactions - cyclizations - chemoselectivity - diastereoselectivity - spiro compounds

    References

  • 3a Boivin B. Tetrahedron  1987,  43:  3309 
    CrossrefGoogle Scholar
  • 3b Perron F. Albizati KF. Chem. Rev.  1989,  89:  1617 
    CrossrefGoogle Scholar
  • 3c Vaillancourt V. Pratt NE. Perron F. Albizati KM. In The Total Synthesis of Natural Products   Vol. 8:  Apsimon JW. John Wiley & sons; New York: 1992.  p.533 
    CrossrefGoogle Scholar
  • 4a Férézou J.-P. Julia M. Liu LW. Li Y. Pancrazi A. Synlett  1991,  614 
    Google Scholar
  • 4b Férézou J.-P. Julia M. Li Y. Liu LW. Pancrazi A. Porteu F. Bull. Soc. Chim. Fr.  1994,  131:  865 
    Google Scholar
  • 4c Férézou J.-P. Julia M. Li Y. Liu LW. Pancrazi A. Bull. Soc. Chim. Fr.  1995,  132:  428 
    Google Scholar
  • 5a For leading reviews on avermectins, see: Blizzard TA. Org. Prep. Proced. Int.  1994,  26:  617 
    CrossrefGoogle Scholar
  • 5b Davies HG. Green RH. Chem. Soc. Rev.  1991,  20:  211 
    CrossrefGoogle Scholar
  • 5c Davies HG. Green RH. Chem. Soc. Rev.  1991,  20:  271 
    CrossrefGoogle Scholar
  • 5d Blizzard T. Fisher MH. Mrozik H. Shih TL. In Recent Progress in the Chemical Synthesis of Antibiotics   Springer-Verlag; Berlin: 1990.  p.65 
    CrossrefGoogle Scholar
  • 5e Crimmins MT. Hollis WG. O’Mahony R. In Studies in Natural Products Chemistry, Stereoselective Synthesis Part A   Vol. 1:  Elsevier; Amsterdam: 1988.  p.435 
    CrossrefGoogle Scholar
  • 5f Davies HG. Green RH. Nat. Prod. Rep.  1986,  3:  87 
    CrossrefGoogle Scholar
  • 6a Werner G. Hagenmaier H. Albert K. Kohlshorn H. Drautz H. Tetrahedron Lett.  1983,  24:  5193 
    CrossrefGoogle Scholar
  • 6b Werner G. Hagenmaier H. Drautz H. Baumgartner A. Zähner H. J. Antibiot.  1984,  37:  110 
    CrossrefGoogle Scholar
  • 6c For total syntheses: Evans DA. Calter MA. Tetrahedron Lett.  1993,  34:  6871 
    CrossrefGoogle Scholar
  • 6d Toshima K. Jyojima T. Yamaguchi H. Murase H. Yoshida T. Matsumura S. Nakata M. Tetrahedron Lett.  1996,  37:  1069 
    CrossrefGoogle Scholar
  • 6e Toshima K. Yamaguchi H. Jyojima T. Noguchi Y. Nakata M. Matsumura S. Tetrahedron Lett.  1996,  37:  1073 
    CrossrefGoogle Scholar
  • 6f Toshima K. Jyojima T. Noguchi Y. Yoshida T. Murase M. Nakata M. Matsumura S. J. Org. Chem.  1997,  62:  3271 
    CrossrefGoogle Scholar
  • 6g Scheidt KA. Tasaka A. Bannister TD. Wendt MD. Roush WR. Angew. Chem. Int. Ed.  1999,  38:  1652 
    CrossrefGoogle Scholar
  • 7a Mukaiyama T. Banno K. Narasaka KJ. J. Am. Chem. Soc.  1974,  96:  7503 
    CrossrefGoogle Scholar
  • 7b For a review: Gennari C. In Comprehensive Organic Synthesis   Vol. 2:  Trost BM. Fleming I. Heathcock CH. Pergamon; New York: 1991.  p.629 
    CrossrefGoogle Scholar
  • 8a Danishefsky SJ. Kitahara H. J. Am. Chem. Soc.  1974,  96:  7807 
    CrossrefGoogle Scholar
  • 8b Danishefsky SJ. Kobayashi S. Kervin JF. J. Org. Chem.  1982,  47:  1983 
    CrossrefGoogle Scholar
  • 8c Danishefsky SJ. Larson E. Askin D. Kato N. J. Am. Chem. Soc.  1985,  107:  1246 
    CrossrefGoogle Scholar
  • 8d Danishefsky SJ. Maring CJ. J. Am. Chem. Soc.  1985,  107:  1269 
    CrossrefGoogle Scholar
  • 9a Reviews: Danishefsky SJ. Aldrichimica Acta  1986,  19:  59 
    Google Scholar
  • 9b Danishefsky SJ. De Ninno MP. Angew. Chem., Int. Ed. Engl.  1987,  26:  15 
    Google Scholar
  • 9c Danishefsky SJ. Chemtracts  1989,  273 
    Google Scholar
  • 10a Chan TH. Brownbridge P. Tetrahedron  1981,  37 Supplement No. 3:  387 
    Google Scholar
  • 10b Chan TH. Brook MA. Tetrahedron Lett.  1985,  25:  2943 
    Google Scholar
  • 11a Danishefsky SJ. Harvey DF. Quallich G. Uang BJ. J. Org. Chem.  1984,  49:  393 
    Article in Thieme ConnectGoogle Scholar
  • 11b Danishefsky SJ. Pearson WH. Harvey DF. Maring CJ. Springer JP. J. Am. Chem. Soc.  1985,  107:  1256 
    Article in Thieme ConnectGoogle Scholar
  • 11c Peterson JR. Kirchhoff EW. Synlett  1990,  394 
    Article in Thieme ConnectGoogle Scholar
  • 12a Mono-activated diols are more prone to [4+2] cycloadditions: Mujica MT. Afonso MM. Galindo A. Palenzuela JA. Tetrahedron  1996,  52:  2167 
    Google Scholar
  • 12b For an example of a true formal asymmetric cycloaddition reaction with 1-methoxy-3-[(trimethylsilyl)oxy]buta-1,2-diene: Schaus SE. Branalt J. Jacobsen EN. J. Org. Chem.  1998,  63:  403 
    Google Scholar
  • 14 Deslongchamps P. Stereoelectronic Effects in Organic Synthesis   Pergamon; New York: 1983. 
    Google Scholar
  • 15a Reviews: Hoffmann RW. Angew. Chem., Int. Ed. Engl.  1987,  26:  489 
    CrossrefGoogle Scholar
  • 15b More focussed on such a triad: Hoffmann RW. Dahmann G. Andersen MW. Synthesis  1994,  629 
    CrossrefGoogle Scholar
  • 15c For a recent solution to this problem: Chemler SR. Roush WR. J. Org. Chem.  1998,  63:  3800 ; and references cited therein
    CrossrefGoogle Scholar
  • 16a

    See Ref. [11b]

  • 16b

    For a related study with substituted mono-activated diene, see Ref. [12]

  • 17 Reetz MT. Kesseler K. J. Chem. Soc., Chem. Commun.  1984,  1079 
    CrossrefGoogle Scholar
  • 18a Heathcock CH. Flippin LA. J. Am. Chem. Soc.  1983,  105:  1667 
    Google Scholar
  • 18b Reetz MT. Tetrahedron Lett.  1984,  25:  729 
    Google Scholar
  • 18c Evans DA. Gage JR. Tetrahedron Lett.  1990,  31:  6129 
    Google Scholar
  • 18d Evans DA. Duffy JL. Dart MJ. Tetrahedron Lett.  1994,  35:  8537 
    Google Scholar
  • 18e Evans DA. Dart MJ. Duffy JL. Tetrahedron Lett.  1994,  35:  8541 
    Google Scholar
  • 18f Gustin DJ. VanNieuwenhze MS. Roush WR. Tetrahedron Lett.  1995,  36:  3443 
    Google Scholar
  • 18g Evans DA. Dart MJ. Duffy JL. Yang MG. Livingston AB. J. Am. Chem. Soc.  1995,  117:  6619 
    Google Scholar
  • 18h Bernardi A. Scolastico C. Chemtracts  1995,  8:  246 ; (research by D. A. Evans)
    Google Scholar
  • 19a Evans DA. Gage JR. Leighton JL. J. Am. Chem. Soc.  1992,  114:  9434  (85:15 syn-Cram-control from syn-a-methyl-b-alkoxy aldehyde corresponding to the C21-C25 fragment of calyculin A)
    Google Scholar
  • 19b Tanimoto N. Gerritz SV. Sawabe A. Noda T. Filla SA. Masamune S. Angew. Chem., Int. Ed. Engl.  1994,  33:  673  (10:1 anti-Cram-chelate control from aldehyde 9 in the presence of TiCl4)
    Google Scholar
  • 19c Paterson I. Cumming JG. Smith JD. Ward RA. Tetrahedron Lett.  1994,  35:  441 
    Google Scholar
  • 19d Paterson I. Cumming JG. Smith JD. Ward RA. Yeung K.-S. Tetrahedron Lett.  1994,  35:  3405 (>97:1 syn-Cram-control from complex anti-a-methyl-b-alkoxy aldehyde corresponding to the C19-C32 fragment of swinholide A and BF3·Et2O)
    Google Scholar
  • 20 Evans DA. Black WC. J. Am. Chem. Soc.  1993,  115:  4497 
    CrossrefGoogle Scholar
  • 21a This aldehyde has been efficiently synthesized in 82% overall yield in a racemic form using Hoppe’s homoaldolization methodology in the presence of TMEDA: Hoppe D. Hanko R. Brönneke A. Lichtenberger F. Van Hülsen E. Chem. Ber.  1985,  118:  2822 
    CrossrefGoogle Scholar
  • 21b This is followed after hydroxyl protection, by ozonolysis of the resulting crude (Z)-vinylcarbamate (see experimental). It is noteworthy that enantioselective access to the corresponding homochiral aldehyde can be readily achieved by replacing TMEDA with (-)-Sparteine: Hoppe I. Hoppe D. Wolff C. Egert E. Herbst R. Angew. Chem., Int. Ed. Engl.  1989,  28:  67 
    CrossrefGoogle Scholar
  • 21c Hoppe D. Zschage O. Angew. Chem., Int. Ed. Engl.  1989,  28:  69 
    CrossrefGoogle Scholar
  • 21d Zschage O. Hoppe D. Tetrahedron  1992,  48:  5657 
    CrossrefGoogle Scholar
  • 22 Ibuka T. Ito Y. Mori Y. Aoyama T. Inubushi Y. Synth. Commun.  1977,  7:  131 
    Google Scholar
  • 23 Evans DA. Dart MJ. Duffy JL. Yang MG. J. Am. Chem. Soc.  1996,  118:  4322 
    CrossrefGoogle Scholar
  • 24a For reviews, see: Reetz MT. Angew. Chem., Int. Ed. Engl.  1989,  28:  67 
    CrossrefGoogle Scholar
  • 24b Reetz MT. Acc. Chem. Res.  1993,  26:  462 
    CrossrefGoogle Scholar
  • 24c

    See also Ref. [17]

    Crossref
  • 24d For 1H NMR evidence of bidentate complexation of multi-complexing Lewis acids: Keck GE. Castellino S. J. Am. Chem. Soc.  1986,  51:  5478 
    CrossrefGoogle Scholar
  • 24e Keck GE. Boden EP. Wiley MR. J. Org. Chem.  1989,  54:  896 
    CrossrefGoogle Scholar
  • 25 Rychnovsky SD. Hoye RC. J. Am. Chem. Soc.  1994,  116:  1753 
    CrossrefGoogle Scholar
  • 27a Uchino K. Yamagiwa Y. Kamikawa T. Tetrahedron Lett.  1985,  26:  1319 
    Google Scholar
  • 27b Peterson JR. Winter TJ. Miller CP. Synth. Commun.  1988,  18:  949 
    Google Scholar
  • 27c For leading references in acetylacetone dianion chemistry and related chemistry, see: Huckin SN. Weiler L. Tetrahedron Lett.  1971,  4835 
    Google Scholar
  • 27d Huckin SN. Weiler L. Can. J. Chem.  1974,  52:  2157 
    Google Scholar
  • 28 Evans DA. Ratz AM. Huff BE. Sheppard GS. J. Am. Chem. Soc.  1995,  117:  3448 
    CrossrefGoogle Scholar
  • 29 For recent synthetic efforts on eight-membered heterocyles, see: Crimmins MT. Choy AL. J. Am. Chem. Soc.  1999,  121:  5653 ; and references cited therein
    Google Scholar
  • 30 Uekim K. Amemiya H. Horino H. Oyamada H. J. Chem. Soc., Chem. Commun.  1988,  414 
    CrossrefGoogle Scholar
  • 31 Taylor EC. Chiang C.-S. Synthesis  1977,  467 
    Article in Thieme ConnectGoogle Scholar
  • 32 LeCocq C. Lallemand J.-Y. J. Chem. Soc., Chem Commun.  1981,  150 
    CrossrefGoogle Scholar
  • 33 Baker R. Head JC. Swain CJ. J. Chem. Soc., Perkin Trans. 1  1988,  85 
    CrossrefGoogle Scholar
1

Current address: Vivien Henryon, Rhône-Poulenc industrialisation, 24 Avenue Jean Jaurès, 69153 Décines-Charpieu, France. E-mail: Vivien.Henryon@CRIT.Rhone-Poulenc.com.

2

Current address: Jean-Pierre Férézou, Far-Manguinhos, Instituto Oswaldo Cruz, Rua Sizenando Nabuco, 100 Manguinhos, CEP 21041-250 Rio de Janeiro/RJ, Brazil, E-Mail: ferezou@gbl.com.br.

13

See Ref. [7] .

26

See Ref. [20] This condensation reaction, performed in the presence of TiCl2(OPr-i)2 led to an excellent Felkin syn-selectivity (>95:5).