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Synlett 2009(3): 333-353  
DOI: 10.1055/s-0028-1087546
ACCOUNT
© Georg Thieme Verlag Stuttgart ˙ New York

The Art of the Soluble: Synthetic Problems from Industry as a Springboard for the Discovery of New Chemical Reactions

Samir Z. Zard
Laboratoire de Synthèse Organique, CNRS UMR 7652, École Polytechnique, 91128 Palaiseau, France
Fax: +33(1)69335972; e-Mail: zard@poly.polytechnique.fr;
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Publikationsverlauf

Received 1 August 2008
Publikationsdatum:
22. Januar 2009 (online)

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Abstract

This account relates the thought processes that went into solving synthetic problems, mostly related to steroids, submitted by industry and, in many cases, the evolution of the solutions into new reactions more generally useful in organic synthesis. A strong emphasis is placed on mechanistic considerations and serendipitous findings as the main basis for constructing working hypotheses from which novel reactions were derived.

1 Introduction

2 Early Steroid Problems

2.1 A Pleasant Encounter with Isocyanides

2.2 The Nitro Route to Corticosteroids

2.3 Explorations in Nitro Chemistry

3 The 16β-Methyl Problem

4 A Problem of Bile Acid Side-Chain Degradation

4.1 Planned and Unexpected Oxazoline Chemistry

4.2 New Reactions of Sulfines

4.3 An Unusual Route to Trifluoromethyl Ketones

5 From Enamides to Radical Chemistry

6 Solutions Waiting for Problems

Key words

steroids - rearrangements - pyrroles - radicals - deoxy­genation

    References

  • 1 Medawar P. Pluto’s Republic   Oxford University Press; Oxford: 1983. 
  • 2 Fieser LF. Fieser M. Steroids   Reinhold; New York: 1959. 
  • 3 For a recent account, see: Pines SH. Org. Process Res. Dev.  2004,  8:  708 
    CrossrefSuche in Google Scholar
  • 4a Peterson DH. Murray HC. Eppstein SH. Reineke LM. Weintraub A. Meister PD. Leigh HM. J. Am. Chem. Soc.  1952,  74:  5933 
    Suche in Google Scholar
  • 4b Eppstein SH. Meister PD. Peterson DH. Murray HC. Leigh HM. Lyttle DA. Reineke LM. Weintraub A. J. Am. Chem. Soc.  1953,  75:  408 
    Suche in Google Scholar
  • 5a Wovcha MG. Antosz FJ. Knight JC. Kominek LA. Pyke TR. Biochim. Biophys. Acta  1978,  539:  308 
    Suche in Google Scholar
  • 5b Marsheck WJ. Kraychy S. Muir RD. Appl. Microbiol.  1972,  23:  72 
    Suche in Google Scholar
  • 6a Barton DHR. Motherwell WB. Zard SZ. J. Chem. Soc., Chem. Commun.  1981,  774 
  • 6b Barton DHR. Motherwell WB. Zard SZ. Nouv. J. Chim.  1982,  6:  295 
    Suche in Google Scholar
  • 7a Barton DHR. Motherwell WB. Zard SZ. J. Chem. Soc., Chem. Commun.  1982,  551 
  • 7b Barton DHR. Motherwell WB. Zard SZ. Bull. Soc. Chim. Fr. II  1983,  61 
  • 8a Barton DHR. Zard SZ. J. Chem. Soc., Chem. Commun.  1985,  1098 
  • 8b Barton DHR. Kervagoret J. Zard SZ. Tetrahedron  1990,  46:  7587 
    Suche in Google Scholar
  • 9 Ono N. Heterocycles  2008,  75:  243 
    CrossrefSuche in Google Scholar
  • 10a Schöllkopf U. Pure Appl. Chem.  1979,  51:  1347 
    Suche in Google Scholar
  • 10b Schöllkopf U. Angew. Chem. Int. Ed. Engl.  1977,  16:  339 
    Suche in Google Scholar
  • 10c Hoppe D. Angew. Chem. Int. Ed. Engl.  1974,  13:  789 
    Suche in Google Scholar
  • 11a Johnstone RAW. In Mechanisms of Molecular Migrations   Vol 2:  Thyagarajan BS. John Wiley & Sons; New York: 1969.  p.249-266  
    Suche in Google Scholar
  • 11b von Schickh O. Apel G. Padeken H.-G. Scharz HH. Segnitz A. Houben-Weyl: Methoden der Organischen Chemie   Vol. X/1:  Thieme; Stuttgart: 1971. 
    Suche in Google Scholar
  • 11c Davies SG. Fox JF. Jones S. Price AJ. Sanz MA. Sellers TGR. Smith AD. Teixeira FC. J. Chem. Soc., Perkin Trans. 1  2002,  1757 ; and references cited therein
  • 12 Boivin J. El Kaim L. Kervagoret J. Zard SZ. J. Chem. Soc., Chem. Commun.  1989,  1006 
    Crossref
  • 13 Alameda-Angulo C. Quiclet-Sire B. Schmidt E. Zard SZ. Org. Lett.  2005,  7:  3489 
    CrossrefSuche in Google Scholar
  • 14a Barlaam B. Boivin J. El Kaim L. Zard SZ. Tetrahedron Lett.  1991,  32:  623 
    Suche in Google Scholar
  • 14b Boivin J. Barlaam B. El Kaim L. Elton-Farr S. Zard SZ. Tetrahedron  1995,  51:  1675 
    Suche in Google Scholar
  • 15a The configuration at C-14 was later corrected, see: Daniewski AR. J. Org. Chem.  1975,  40:  3127 
    Suche in Google Scholar
  • 15b Daniewski AR. Guzewska M. Kocor M. J. Org. Chem.  1978,  43:  349 
    Suche in Google Scholar
  • 16a Phillips ED. Whitham GH. Tetrahedron Lett.  1993,  34:  2537 
    Suche in Google Scholar
  • 16b Phillips ED. Whitham GH. Tetrahedron Lett.  1993,  34:  2544 
    Suche in Google Scholar
  • 16c Smith TAK. Whitham GH. J. Chem. Soc., Perkin Trans. 1  1989,  313 
  • 16d Smith TAK. Whitham GH. J. Chem. Soc., Perkin Trans. 1  1989,  319 
  • 16e Knight DJ. Lin P. Whitham GH. J. Chem. Soc., Perkin Trans. 1  1987,  2707 
  • 17 Barlaam B. Boivin J. Zard SZ. Tetrahedron Lett.  1990,  31:  7429 
    CrossrefSuche in Google Scholar
  • 18 Alameda-Angulo C. Ph.D. Thesis   École Polytechnique; Palaiseau, France: .  p.2006 
  • 19a Barton DHR. Motherwell WB. Simon ES. Zard SZ. J. Chem. Soc., Chem. Commun.  1984,  337 
  • 19b Barton DHR. Motherwell WB. Simon ES. Zard SZ.
    J. Chem. Soc., Perkin Trans. 1  1986,  2243 
  • 20 Boivin J. Fouquet E. Zard SZ. Tetrahedron Lett.  1990,  31:  85 
    CrossrefSuche in Google Scholar
  • 21 Lamy E. Lüthi P. Paturel C. Winkler T. Jung PMJ. Tetrahedron Lett.  2006,  47:  5657 
    CrossrefSuche in Google Scholar
  • 22a Lukin KA. Narayanan BA. Tetrahedron  2002,  58:  215 
    Suche in Google Scholar
  • 22b Esteban J. Costa AM. Urpi F. Vilarrasa J. Tetrahedron Lett.  2004,  45:  5563 
    Suche in Google Scholar
  • 23 Barton DHR. Motherwell WB. Zard SZ. Tetrahedron Lett.  1984,  25:  3707 
    CrossrefSuche in Google Scholar
  • 24 Lednicer D. Mitscher LA. The Organic Chemistry of Drug Synthesis   Wiley Interscience; New York: 1977. 
  • 25a Laurent H. Wiechert R. In Organic Reactions in Steroid Chemistry   Fried J. Edwards JA. Van Nostrand Reinhold; New York: 1972.  Chapter 10.
  • 25b Rausser R. Lyncheski AM. Harris H. Grocela R. Murrill N. Bellamy E. Ferchinger D. Gebert W. Herzog HL. Hershberg EB. Oliveto EP. J. Org. Chem.  1966,  31:  26 
    Suche in Google Scholar
  • 25c Batres E. Cardenas T. Edwards JA. Monroy G. Mancera O. Djerrassi C. Ringold HJ. J. Org. Chem.  1961,  26:  871 
    Suche in Google Scholar
  • 25d Taub D. Hoffsommer RD. Wendler NL. J. Org. Chem.  1964,  29:  3486 
    Suche in Google Scholar
  • 26 Boivin J. Chauvet C. Zard SZ. Tetrahedron Lett.  1992,  33:  4913 
    CrossrefSuche in Google Scholar
  • 27 Chauvet C. Ph.D. Thesis   Université Paris XI; Orsay: France.  p.1991 
  • 28 Barton DHR. Motherwell WB. Wozniak J. Zard SZ. J. Chem. Soc., Perkin Trans. 1  1985,  1865 
    Crossref
  • 29a Barton DHR. Wozniak J. Zard SZ. J. Chem. Soc., Chem. Commun.  1987,  1383 
  • 29b Barton DHR. Wozniak J. Zard SZ. Tetrahedron  1989,  45:  3741 
    Suche in Google Scholar
  • 30 Van Rheenen V. J. Chem. Soc., Chem. Commun.  1969,  314 
  • 31 Piatak DM. Wicha J. Chem. Rev.  1978,  78:  199 
    CrossrefSuche in Google Scholar
  • 32a Boivin J. El Kaim L. Zard SZ. Tetrahedron Lett.  1992,  33:  1285 
    Suche in Google Scholar
  • 32b Boivin J. El Kaim L. Zard SZ. Tetrahedron  1995,  51:  2573 
    Suche in Google Scholar
  • 32c Boivin J. El Kaim L. Zard SZ. Tetrahedron  1995,  51:  2585 
    Suche in Google Scholar
  • 33 For a review, see: Zard SZ. Org. Biomol. Chem.  2007,  5:  205 
    CrossrefPubMedSuche in Google Scholar
  • 34 Trimble LA. Street IP. Perrier H. Trembley NM. Weech PK. Bernstein MA. Biochemistry  1993,  32:  12560 
    CrossrefSuche in Google Scholar
  • 35 Reeves JT. Gallou F. Song JJ. Tan Z. Lee H. Yee NK. Senanayake CH. Tetrahedron Lett.  2007,  48:  189 
    CrossrefSuche in Google Scholar
  • 37 El Kaim L. Ph.D. Thesis   Université Paris XI; Orsay: France.  p.1992 
  • 38 Boar RB. McGhie JF. Robinson M. Barton DHR. Horwell DC. Stick RV. J. Chem. Soc., Perkin Trans. 1  1975,  1237 
    Crossref
  • 39 Barton DHR. Zard SZ. J. Chem. Soc., Perkin Trans. 1  1985,  2191 
    Crossref
  • 40 Laso NM. Quiclet-Sire B. Zard SZ. Tetrahedron Lett.  1996,  37:  1605 
    CrossrefSuche in Google Scholar
  • 41 Boar RB. Jetuah FK. McGhie JF. Robinson M. Barton DHR. J. Chem. Soc., Perkin Trans. 1  1977,  2163 
    Crossref
  • 42 Boivin J. Schiano A.-M. Zard SZ. Tetrahedron Lett.  1992,  33:  7849 
    CrossrefSuche in Google Scholar
  • 43 Boivin J. Fouquet E. Zard SZ. Tetrahedron  1994,  50:  1757 
    CrossrefSuche in Google Scholar
  • 44 Boivin J. Schiano A.-M. Zard SZ. Zhang H. Tetrahedron Lett.  1999,  40:  4531 
    CrossrefSuche in Google Scholar
  • 45 Boivin J. Yousfi M. Zard SZ. Tetrahedron Lett.  1994,  35:  5629 
    CrossrefSuche in Google Scholar
  • 46 Cassayre J. Dauge D. Zard SZ. Synlett  2000,  471 
    Thieme Connect
  • 47 Quiclet-Sire B. Saunier J.-B. Zard SZ. Tetrahedron Lett.  1996,  37:  1397 
    CrossrefSuche in Google Scholar
  • 48a Cassayre J. Quiclet-Sire B. Saunier J.-B. Zard SZ. Tetrahedron  1998,  54:  1029 
    Suche in Google Scholar
  • 48b Cassayre J. Zard SZ. Synlett  1999,  501 
  • 49 Cassayre J. Quiclet-Sire B. Saunier J.-B. Zard SZ. Tetrahedron Lett.  1998,  39:  8995 
    CrossrefSuche in Google Scholar
  • 50 Boivin J. Yousfi M. Zard SZ. Tetrahedron Lett.  1994,  35:  9553 
    CrossrefSuche in Google Scholar
  • 51 Boivin J. Yousfi M. Zard SZ. Tetrahedron Lett.  1997,  38:  5985 
    CrossrefSuche in Google Scholar
  • 52 Duncia JV. Piece ME. Santella JB. J. Org. Chem.  1991,  56:  2395 
    CrossrefSuche in Google Scholar
  • 53 Boivin J. Husinec S. Zard SZ. Tetrahedron  1995,  51:  11737 
    CrossrefSuche in Google Scholar
  • 54 Barton DHR. McCombie SW. J. Chem. Soc., Perkin Trans. 1  1975,  1574 
    Crossref
  • 55 Quiclet-Sire B. Zard SZ. Tetrahedron Lett.  1998,  39:  9435 
    CrossrefSuche in Google Scholar
  • 56 Spassova N. Ph.D. Thesis   École Polytechnique; Palaiseau: France.  p.2000 
  • 57 Siddiqui MA. Driscoll JS. Abushanab E. Kelley JA. Barchi JJ. Marquez VE. Nucleosides Nucleotides  2000,  19:  1 
    Suche in Google Scholar
  • For reviews on xanthate transfer chemistry, see:
  • 58a Zard SZ. Angew. Chem., Int. Ed. Engl.  1997,  36:  672 
    Suche in Google Scholar
  • 58b Zard SZ. In Radicals in Organic Synthesis   Vol. 1:  Renaud P. Sibi MP. Wiley-VCH; Weinheim: 2001.  p.90 
    Suche in Google Scholar
  • 58c Quiclet-Sire B. Zard SZ. Chem. Eur. J.  2006,  12:  6002 
    Suche in Google Scholar
  • 58d Quiclet-Sire B. Zard SZ. Top. Curr. Chem.  2006,  264:  201 
    Suche in Google Scholar
  • 58e See also ref.
  • For recent reviews, see:
  • 59a Handbook of RAFT Polymerization   Barner-Kowollik C. Wiley-VCH; Weinheim: 2008. 
  • 59b Moad G. Rizzardo E. Thang SH. Aust. J. Chem.  2005,  58:  379 
    Suche in Google Scholar
  • 59c Perrier S. Takolpuckdee T. J. Polym. Sci., Part A: Polym. Chem.  2005,  43:  5347 
    Suche in Google Scholar
  • 60a Georghe A. Quiclet-Sire B. Vila X. Zard SZ. Org. Lett.  2005,  7:  1653 
    Suche in Google Scholar
  • 60b Georghe A. Quiclet-Sire B. Vila X. Zard SZ. Tetrahedron  2007,  63:  7187 
    Suche in Google Scholar
  • 61a Bacqué E. El Qacemi M. Zard SZ. Org. Lett.  2004,  6:  3671 
    Suche in Google Scholar
  • 61b El Qacemi M. Ph.D. Thesis   École Polytechnique, Palaiseau; France: 2005. 
  • 62a Ashton MJ. Lawrence C. Karlsson J.-A. Stuttle KAJ. Newton CG. Vacher BYJ. Webber S. Whitnall MJ. J. Med. Chem.  1996,  39:  4888 
    Suche in Google Scholar
  • 62b For a review, see: Brattsand R. Selroos O. In Drugs and Lungs   Page CP. Metzger WJ. Raven; New York: 1994.  p.101-220  
  • 63 Quiclet-Sire B. Zard SZ. Tetrahedron Lett.  1998,  39:  1073 
    Suche in Google Scholar
36

Quiclet-Sire, B.; Zard, S. Z. unpublished results.