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

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.

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

References

<A NAME="RZ08601SS-1">1</A>

Current address: Vivien Henryon, Rhône-Poulenc industrialisation, 24 Avenue Jean Jaurès, 69153 Décines-Charpieu, France. E-mail: [e-mail].

<A NAME="RZ08601SS-2">2</A>

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: [e-mail].

<A NAME="RZ08601SS-3A">3a</A> Boivin B. Tetrahedron  1987,  43:  3309 

<A NAME="RZ08601SS-3B">3b</A> Perron F. Albizati KF. Chem. Rev.  1989,  89:  1617 

<A NAME="RZ08601SS-3C">3c</A> 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 

<A NAME="RZ08601SS-4A">4a</A> Férézou J.-P. Julia M. Liu LW. Li Y. Pancrazi A. Synlett  1991,  614 

<A NAME="RZ08601SS-4B">4b</A> Férézou J.-P. Julia M. Li Y. Liu LW. Pancrazi A. Porteu F. Bull. Soc. Chim. Fr.  1994,  131:  865 

<A NAME="RZ08601SS-4C">4c</A> Férézou J.-P. Julia M. Li Y. Liu LW. Pancrazi A. Bull. Soc. Chim. Fr.  1995,  132:  428 

<A NAME="RZ08601SS-5A">5a</A> For leading reviews on avermectins, see: Blizzard TA. Org. Prep. Proced. Int.  1994,  26:  617 

<A NAME="RZ08601SS-5B">5b</A> Davies HG. Green RH. Chem. Soc. Rev.  1991,  20:  211 

<A NAME="RZ08601SS-5C">5c</A> Davies HG. Green RH. Chem. Soc. Rev.  1991,  20:  271 

<A NAME="RZ08601SS-5D">5d</A> Blizzard T. Fisher MH. Mrozik H. Shih TL. In Recent Progress in the Chemical Synthesis of Antibiotics   Springer-Verlag; Berlin: 1990.  p.65 

<A NAME="RZ08601SS-5E">5e</A> Crimmins MT. Hollis WG. O’Mahony R. In Studies in Natural Products Chemistry, Stereoselective Synthesis Part A   Vol. 1:  Elsevier; Amsterdam: 1988.  p.435 

<A NAME="RZ08601SS-5F">5f</A> Davies HG. Green RH. Nat. Prod. Rep.  1986,  3:  87 

<A NAME="RZ08601SS-6A">6a</A> Werner G. Hagenmaier H. Albert K. Kohlshorn H. Drautz H. Tetrahedron Lett.  1983,  24:  5193 

<A NAME="RZ08601SS-6B">6b</A> Werner G. Hagenmaier H. Drautz H. Baumgartner A. Zähner H. J. Antibiot.  1984,  37:  110 

<A NAME="RZ08601SS-6C">6c</A> For total syntheses: Evans DA. Calter MA. Tetrahedron Lett.  1993,  34:  6871 

<A NAME="RZ08601SS-6D">6d</A> Toshima K. Jyojima T. Yamaguchi H. Murase H. Yoshida T. Matsumura S. Nakata M. Tetrahedron Lett.  1996,  37:  1069 

<A NAME="RZ08601SS-6E">6e</A> Toshima K. Yamaguchi H. Jyojima T. Noguchi Y. Nakata M. Matsumura S. Tetrahedron Lett.  1996,  37:  1073 

<A NAME="RZ08601SS-6F">6f</A> Toshima K. Jyojima T. Noguchi Y. Yoshida T. Murase M. Nakata M. Matsumura S. J. Org. Chem.  1997,  62:  3271 

<A NAME="RZ08601SS-6G">6g</A> Scheidt KA. Tasaka A. Bannister TD. Wendt MD. Roush WR. Angew. Chem. Int. Ed.  1999,  38:  1652 

<A NAME="RZ08601SS-7A">7a</A> Mukaiyama T. Banno K. Narasaka KJ. J. Am. Chem. Soc.  1974,  96:  7503 

<A NAME="RZ08601SS-7B">7b</A> For a review: Gennari C. In Comprehensive Organic Synthesis   Vol. 2:  Trost BM. Fleming I. Heathcock CH. Pergamon; New York: 1991.  p.629 

<A NAME="RZ08601SS-8A">8a</A> Danishefsky SJ. Kitahara H. J. Am. Chem. Soc.  1974,  96:  7807 

<A NAME="RZ08601SS-8B">8b</A> Danishefsky SJ. Kobayashi S. Kervin JF. J. Org. Chem.  1982,  47:  1983 

<A NAME="RZ08601SS-8C">8c</A> Danishefsky SJ. Larson E. Askin D. Kato N. J. Am. Chem. Soc.  1985,  107:  1246 

<A NAME="RZ08601SS-8D">8d</A> Danishefsky SJ. Maring CJ. J. Am. Chem. Soc.  1985,  107:  1269 

<A NAME="RZ08601SS-9A">9a</A> Reviews: Danishefsky SJ. Aldrichimica Acta  1986,  19:  59 

<A NAME="RZ08601SS-9B">9b</A> Danishefsky SJ. De Ninno MP. Angew. Chem., Int. Ed. Engl.  1987,  26:  15 

<A NAME="RZ08601SS-9C">9c</A> Danishefsky SJ. Chemtracts  1989,  273 

<A NAME="RZ08601SS-10A">10a</A> Chan TH. Brownbridge P. Tetrahedron  1981,  37 Supplement No. 3:  387 

<A NAME="RZ08601SS-10B">10b</A> Chan TH. Brook MA. Tetrahedron Lett.  1985,  25:  2943 

<A NAME="RZ08601SS-11A">11a</A> Danishefsky SJ. Harvey DF. Quallich G. Uang BJ. J. Org. Chem.  1984,  49:  393 

<A NAME="RZ08601SS-11B">11b</A> Danishefsky SJ. Pearson WH. Harvey DF. Maring CJ. Springer JP. J. Am. Chem. Soc.  1985,  107:  1256 

<A NAME="RZ08601SS-11C">11c</A> Peterson JR. Kirchhoff EW. Synlett  1990,  394 

<A NAME="RZ08601SS-12A">12a</A> Mono-activated diols are more prone to [4+2] cycloadditions: Mujica MT. Afonso MM. Galindo A. Palenzuela JA. Tetrahedron  1996,  52:  2167 

<A NAME="RZ08601SS-12B">12b</A> 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 

<A NAME="RZ08601SS-13">13</A>

See Ref. [7] .

<A NAME="RZ08601SS-14">14</A> Deslongchamps P. Stereoelectronic Effects in Organic Synthesis   Pergamon; New York: 1983. 

<A NAME="RZ08601SS-15A">15a</A> Reviews: Hoffmann RW. Angew. Chem., Int. Ed. Engl.  1987,  26:  489 

<A NAME="RZ08601SS-15B">15b</A> More focussed on such a triad: Hoffmann RW. Dahmann G. Andersen MW. Synthesis  1994,  629 

<A NAME="RZ08601SS-15C">15c</A> For a recent solution to this problem: Chemler SR. Roush WR. J. Org. Chem.  1998,  63:  3800 ; and references cited therein

<A NAME="RZ08601SS-16A">16a</A>

See Ref. [11b]

<A NAME="RZ08601SS-16B">16b</A>

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

<A NAME="RZ08601SS-17">17</A> Reetz MT. Kesseler K. J. Chem. Soc., Chem. Commun.  1984,  1079 

<A NAME="RZ08601SS-18A">18a</A> Heathcock CH. Flippin LA. J. Am. Chem. Soc.  1983,  105:  1667 

<A NAME="RZ08601SS-18B">18b</A> Reetz MT. Tetrahedron Lett.  1984,  25:  729 

<A NAME="RZ08601SS-18C">18c</A> Evans DA. Gage JR. Tetrahedron Lett.  1990,  31:  6129 

<A NAME="RZ08601SS-18D">18d</A> Evans DA. Duffy JL. Dart MJ. Tetrahedron Lett.  1994,  35:  8537 

<A NAME="RZ08601SS-18E">18e</A> Evans DA. Dart MJ. Duffy JL. Tetrahedron Lett.  1994,  35:  8541 

<A NAME="RZ08601SS-18F">18f</A> Gustin DJ. VanNieuwenhze MS. Roush WR. Tetrahedron Lett.  1995,  36:  3443 

<A NAME="RZ08601SS-18G">18g</A> Evans DA. Dart MJ. Duffy JL. Yang MG. Livingston AB. J. Am. Chem. Soc.  1995,  117:  6619 

<A NAME="RZ08601SS-18H">18h</A> Bernardi A. Scolastico C. Chemtracts  1995,  8:  246 ; (research by D. A. Evans)

<A NAME="RZ08601SS-19A">19a</A> 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)

<A NAME="RZ08601SS-19B">19b</A> 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)

<A NAME="RZ08601SS-19C">19c</A> Paterson I. Cumming JG. Smith JD. Ward RA. Tetrahedron Lett.  1994,  35:  441 

<A NAME="RZ08601SS-19D">19d</A> 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)

<A NAME="RZ08601SS-20">20</A> Evans DA. Black WC. J. Am. Chem. Soc.  1993,  115:  4497 

<A NAME="RZ08601SS-21A">21a</A> 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 

<A NAME="RZ08601SS-21B">21b</A> 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 

<A NAME="RZ08601SS-21C">21c</A> Hoppe D. Zschage O. Angew. Chem., Int. Ed. Engl.  1989,  28:  69 

<A NAME="RZ08601SS-21D">21d</A> Zschage O. Hoppe D. Tetrahedron  1992,  48:  5657 

<A NAME="RZ08601SS-22">22</A> Ibuka T. Ito Y. Mori Y. Aoyama T. Inubushi Y. Synth. Commun.  1977,  7:  131 

<A NAME="RZ08601SS-23">23</A> Evans DA. Dart MJ. Duffy JL. Yang MG. J. Am. Chem. Soc.  1996,  118:  4322 

<A NAME="RZ08601SS-24A">24a</A> For reviews, see: Reetz MT. Angew. Chem., Int. Ed. Engl.  1989,  28:  67 

<A NAME="RZ08601SS-24B">24b</A> Reetz MT. Acc. Chem. Res.  1993,  26:  462 

<A NAME="RZ08601SS-24C">24c</A>

See also Ref. [17]

<A NAME="RZ08601SS-24D">24d</A> For ¹H NMR evidence of bidentate complexation of multi-complexing Lewis acids: Keck GE. Castellino S. J. Am. Chem. Soc.  1986,  51:  5478 

<A NAME="RZ08601SS-24E">24e</A> Keck GE. Boden EP. Wiley MR. J. Org. Chem.  1989,  54:  896 

<A NAME="RZ08601SS-25">25</A> Rychnovsky SD. Hoye RC. J. Am. Chem. Soc.  1994,  116:  1753 

<A NAME="RZ08601SS-26">26</A>

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

<A NAME="RZ08601SS-27A">27a</A> Uchino K. Yamagiwa Y. Kamikawa T. Tetrahedron Lett.  1985,  26:  1319 

<A NAME="RZ08601SS-27B">27b</A> Peterson JR. Winter TJ. Miller CP. Synth. Commun.  1988,  18:  949 

<A NAME="RZ08601SS-27C">27c</A> For leading references in acetylacetone dianion chemistry and related chemistry, see: Huckin SN. Weiler L. Tetrahedron Lett.  1971,  4835 

<A NAME="RZ08601SS-27D">27d</A> Huckin SN. Weiler L. Can. J. Chem.  1974,  52:  2157 

<A NAME="RZ08601SS-28">28</A> Evans DA. Ratz AM. Huff BE. Sheppard GS. J. Am. Chem. Soc.  1995,  117:  3448 

<A NAME="RZ08601SS-29">29</A> For recent synthetic efforts on eight-membered heterocyles, see: Crimmins MT. Choy AL. J. Am. Chem. Soc.  1999,  121:  5653 ; and references cited therein

<A NAME="RZ08601SS-30">30</A> Uekim K. Amemiya H. Horino H. Oyamada H. J. Chem. Soc., Chem. Commun.  1988,  414 

<A NAME="RZ08601SS-31">31</A> Taylor EC. Chiang C.-S. Synthesis  1977,  467 

<A NAME="RZ08601SS-32">32</A> LeCocq C. Lallemand J.-Y. J. Chem. Soc., Chem Commun.  1981,  150 

<A NAME="RZ08601SS-33">33</A> Baker R. Head JC. Swain CJ. J. Chem. Soc., Perkin Trans. 1  1988,  85