Intramolecular Haloetherification of Ene- and Diene-Acetals:
Asymmetric Synthesis Involving Chiral Oxonium Ion Intermediates

Abstract

Asymmetric processes, taking place via the intermediacy of chiral oxonium ions arising from intramolecular haloetherification reactions of chiral ene- and diene-acetals of optically pure C ₂-symmetric hydrobenzoine, have been developed. A novel, double intramolecular haloetherification process was observed. The asymmetric reactions developed in this effort were applied to the synthesis of several natural products, including solenopsin A, (cis-6-methyltetrahydropyran-2-yl)acetic acid, the pheromone of the wasp Paravespula vulgaris, rubrenolide, rubrynolide, scyphostatin, cryptocaryone, Sch 642305, and clavolonine. The strategies used in these syntheses involved a new concept called ‘chiral auxiliary multiple-use methodology’. In addition, intramolecular haloetherification reactions of ene-acetals, derived from chiral optically pure norbornene aldehydes and meso-diols, were applied to asymmetric desymmetrization of meso-diols. Finally, a new method for the resolution of racemic norbornene aldehydes, utilizing chiral ene-acetal oxonium ion intermediates produced from optically pure hydrobenzoin, was developed.

1 Introduction

2 Haloetherification of Ene-Acetals of Chiral Nonracemic Diols

2.1 Reactions of Ene-Acetals Leading to Asymmetric Synthesis of 1,4- and 1,5-Diols

2.2 Reactions of Ene-Ketals Containing Nucleophilic Functional Groups

2.3 Applications to Natural Products Syntheses

2.3.1 Synthesis of the Wasp Paravespula vulgaris Pheromone

3 Haloetherification of σ-Symmetric Diene-Acetals

3.1 Cyclic σ-Diene-Acetals

3.2 Double Iodoetherification Reactions of Acyclic Diene-­Acetals

3.2.1 Acyclic Diene-Acetals

3.2.2 Acyclic Diene-Ketals

3.3 Natural Products Syntheses

3.3.1 Application of Double Intramolecular Haloetherification Reactions of Acyclic Diene-Acetal to the Syntheses of ­Rubrenolide and Rubrynolide

3.3.2 The Use of Cyclic Diene-Acetals

3.3.3 Chiral Auxiliary Multiple-Use Methodology as a New Concept in Natural Products Synthesis

4 Reactions of the Ene-Acetals, Derived from Chiral Non­racemic Ene-Aldehydes and a Non-Optically Active Diol

4.1 Asymmetric Desymmetrization of meso-1,2-Diols

4.2 Resolution of Racemic Norbornene Aldehydes

4.3 Asymmetric Desymmetrization of meso-1,3- and -1,4-Diols

5 Conclusion

Key words

intramolecular reactions - acetals - asymmetric synthesis - chiral auxiliaries - natural product synthesis

References

• 1a Wuts PGM. Greene TW. In Green’s Protective Groups in Organic Synthesis   4th ed.:  John Wiley & Sons, Inc; Hoboken / NJ: 2006.  p.431 
• 1b Hanson JR. In Protecting Groups in Organic Synthesis   1st ed.:  Blackwell Science, Inc; Malden / MA: 1999.  p.37 
• 1c Kocienski PJ. Protecting Groups   1st ed.:  Georg Thieme Verlag; Stuttgart: 1994.  p.156 
• 2 Mukaiyama T. Organic Reactions  1982,  28:  203 
• For reviews on asymmetric synthesis using the chiral C ₂-symmetric acetals, see:
• 3a Alexakis A. Mangeny P. Tetrahedron: Asymmetry  1990,  1:  477 
• 3b Fujioka H. Kita Y. Studies in Natural Product Chemistry   Vol. 14:  . Elsevier; Amsterdam: 1994.  p.469 
• 4a Fujioka H. Kitagawa H. Matsunaga N. Nagatomi Y. Kita Y. Tetrahedron Lett.  1996,  37:  2245 
• 4b Fujioka H. Kitagawa H. Nagatomi Y. Kita Y. J. Org. Chem.  1996,  61:  7309 
• 5 Wang Z.-M. Sharpless KB. J. Org. Chem.  1994,  59:  8302 
• 6 Fujioka H. Nakahara K. Hirose H. Hirano K. Oki T. Kita Y. Chem. Commun.  2011,  47:  1060 
• 7a Kita Y. Namubu H. Ramesh NG. Anilkumar G. Matsugi M. Org. Lett.  2001,  3:  1157 
• 7b Namubu H. Anilkumar G. Matsugi M. Kita Y. Tetrahedron  2003,  59:  77 
• 7c Namubu H. Alinejad AH. Fujioka H. Kita Y. Tetrahedron Lett.  2004,  45:  8927 
• 8a Fujioka H. Ohba Y. Hirose H. Murai K. Kita Y. Org. Lett.  2005,  7:  3303 
• 8b Fujioka H. Hirose H. Ohba Y. Murai K. Nakahara K. Kita Y. Tetrahedron  2007,  63:  625 
• 8c Maulide N. Vanherck J.-C. Gautier A. Marko IE. Acc. Chem. Res.  2007,  40:  381 
• 9 Francke W. Hindorf G. Reith W. Angew. Chem., Int. Ed. Engl.  1978,  17:  862 
• 10 Fujioka H. Kotoku N. Sawama Y. Kitagawa H. Ohba Y. Wang T.-L. Nagatomi Y. Kita Y. Chem. Pharm. Bull.  2005,  53:  952 
• 11a Fujioka H. Ohba Y. Hirose H. Murai K. Kita Y. Angew. Chem. Int. Ed.  2005,  44:  734 
• 11b Fujioka H. Ohba Y. Hirose H. Nakahara K. Murai K. Kita Y. Tetrahedron  2008,  64:  4233 
• 12a Franca NC. Gottlieb OR. Coxon DT. Ollis WD. J. Chem. Soc., Chem. Commun.  1972,  514 
• 12b Franca NC. Gottlieb OR. Coxon DT. Phytochemistry  1977,  16:  257 
• 13 Fujioka H. Kotoku N. Sawama Y. Nagatomi Y. Kita Y. Tetrahedron Lett.  2002,  43:  4825 
• 14 Fujioka H. Sawama Y. Kotoku N. Ohnaka T. Okitsu T. Murata N. Kubo O. Li R. Kita Y. Chem. Eur. J.  2007,  13:  10225 
• 15a Tanaka M. Nara F. Suzuki-Konagai K. Hosoya T. Ogita T. J. Am. Chem. Soc.  1997,  119:  7871 
• 15b Nara F. Tanaka M. Hosoya T. Suzuki-Konagai K. Ogita T. J. Antibiot.  1999,  52:  525 
• 15c Nara F. Tanaka M. Masuda-Inoue S. Yamamoto Y. Doi-Yoshioka H. Suzuki-Konagai K. Kumakura S. Ogita T. J. Antibiot.  1999,  52:  531 
• 15d Saito S. Tanaka N. Fujimoto K. Kogen H. Org. Lett.  2000,  2:  505 
• For total syntheses by other groups, see:
• 16a Inoue M. Yokota W. Murugesh MG. Izuhara T. Katoh T. Angew. Chem. Int. Ed.  2004,  43:  4207 
• 16b Takagi R. Miyanaga W. Tojo K. Tsuyumine S. Ohkata K. J. Org. Chem.  2007,  72:  4117 
• After our work, the following papers appeared:
• 16c Inoue M. Yokota W. Katoh T. Synthesis  2007,  622 
• 16d Pitsinos E. Athinaios N. Xu Z. Wang G. Neigishi E. Chem. Commun.  2010,  46:  2200 
• 17a Fujioka H. Sawama Y. Murata N. Okitsu T. Kubo O. Matsuda T. Kita Y. J. Am. Chem. Soc.  2004,  126:  11800 
• 17b Fujioka H. Okitsu T. Sawama Y. Murata N. Li R. Kita Y. J. Am. Chem. Soc.  2006,  128:  5930 
• 18 Hoye TR. Tennakoon MA. Org. Lett.  2000,  2:  1481 
• 19a Mukaiyama T. Matsuo J. Kitagawa H. Chem. Lett.  2000,  1250 
• 19b Mukaiyama T. Matsuo J. Yanagisawa M. Chem. Lett.  2000,  1072 
• 20 Fujioka H. Nakahara K. Oki T. Hirano K. Hayashi T. Kita Y. Tetrahedron Lett.  2010,  51:  1945 
• 21a Govindachari TR. Parthasarathy PC. Tetrahedron Lett.  1972,  3419 
• 21b Govindachari TR. Parthasarathy PC. Desai HK. Shanbhag MN. Tetrahedron  1973,  29:  3091 
• 22 Maddry JA. Joshi BS. Newton MG. Pelletier SW. Parthasarathy PC. Tetrahedron Lett.  1985,  26:  5491 
• 23a Dumontet V. Gaspard C. Hung NV. Fahy J. Tchertanov L. Sévenet T. Guéritte F. Tetrahedron  2001,  57:  6189 
• 23b Meragelman TL. Scudiero DA. Davis RE. Staudt LM. McCloud TG. Cardellina JH. Shoemaker RH. J. Nat. Prod.  2009,  72:  336 
• 24 Hanessian S. Wong DH. Therien M. Synthesis  1981,  394 
• 25 Fujioka H. Ohba Y. Nakahara K. Takatsuji M. Murai K. Ito M. Kita Y. Org. Lett.  2007,  9:  5605 
• 26 Chu M. Mierzwa R. Xu L. He L. Terracciano J. Patel M. Gullo V. Black T. Zhao W. Chan T.-M. McPhail AT. J. Nat. Prod.  2003,  66:  1527 
• 27 Jayasuriya H. Zink DL. Polishook JD. Bills GF. Dombrowski AW. Genilloud O. Pelacz FF. Herranz L. Quamina D. Lingham RB. Danzeizem R. Graham PL. Tomassini JE. Singh SB. Chem. Biodivers.  2005,  2:  112 
• For total synthesis by other groups, see:
• 28a Mehta G. Shinde HM. Chem. Commun.  2005,  3703 
• 28b Ishigami K. Katsuta R. Watanabe H. Tetrahedron  2006,  62:  2224 
• 28c Snider B. Zhou J. Org. Lett.  2006,  8:  1283 
• 28d Wilson EM. Trauner D. Org. Lett.  2007,  9:  1327 
• After our work, the following papers appeared:
• 28e García-Fortanet J. Cards M. Marco JA. Tetrahedron  2007,  63:  12131 
• 28f Chakraborty TK. Samanta R. Kumar PK. Tetrahedron  2009,  65:  6925 
• 28g Dermenci A. Selig PS. Domaoal RA. Spasov KA. Anderson KS. Miller SJ. Chem. Sci.  2011,  2:  1568 
• 29 Yu M. Alonso-Galicia M. Sun C.-W. Roman RJ. Ono N. Hirano H. Ishimoto T. Reddy YK. Katipally KR. Reddy KM. Gopal VR. Yu J. Yakhi M. Frank JR. Bioorg. Med. Chem.  2003,  11:  2803 
• 30 Corey EJ. Nicolaou KC. J. Am. Chem. Soc.  1974,  96:  5614 
• 31 Nakahara K. Hirano K. Maehata R. Kita Y. Fujioka H. Org. Lett.  2011,  13:  2015 
• 32a Burnell RH. Taylor DR. Chem. Ind. (London)  1960,  1239 
• 32b Burnell RH. Mootoo BS. Can. J. Chem.  1961,  39:  1090 
• 33a Wenkert E. Broka CA. J. Chem. Soc., Chem. Commun.  1984,  714 
• 33b Evans DA. Scheerer JR. Angew. Chem. Int. Ed.  2005,  44:  6038 
• 33c Laemmerhold KM. Breit B. Angew. Chem. Int. Ed.  2010,  49:  2367 
• 34a Fujioka H. Nagatomi Y. Kitagawa H. Kita Y. J. Am. Chem. Soc.  1997,  119:  12016 
• 34b Kita Y. Nagatomi Y. Kitagawa H. Fujioka H. Electronic Conference on Heterocyclic Chemistry (ECHET 98)  1998, CD-ROM 011
• 34c Fujioka H. Nagatomi Y. Kotoku N. Kitagawa H. Kita Y. Tetrahedron Lett.  1998,  39:  7309 
• 34d Fujioka H. Nagatomi Y. Kotoku N. Kitagawa H. Kita Y. Tetrahedron  2000,  56:  10141 
• 35a Fujioka H. Kotoku N. Nagatomi Y. Kita Y. Tetrahedron Lett.  2000,  41:  1829 
• 35b Fujioka H. Kotoku N. Fujita T. Inoguchi R. Murai K. Nagatomi Y. Sawama Y. Kita Y. Chirality  2003,  15:  60 
• 36 Fujioka H. Fujita T. Kotoku N. Ohba Y. Hiramatsu A. Kita Y. Chem. Eur. J.  2004,  10:  5386