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

Samir Z. Zard

doi:10.1055/s-0028-1087546

ACCOUNT

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;

Abstract

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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

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Referenzen

References

<A NAME="RA50708ST-1">1</A> Medawar P. Pluto’s Republic Oxford University Press; Oxford: 1983.

<A NAME="RA50708ST-2">2</A> Fieser LF. Fieser M. Steroids Reinhold; New York: 1959.

<A NAME="RA50708ST-3">3</A> For a recent account, see: Pines SH. Org. Process Res. Dev. 2004, 8: 708

<A NAME="RA50708ST-4A">4a</A> Peterson DH. Murray HC. Eppstein SH. Reineke LM. Weintraub A. Meister PD. Leigh HM. J. Am. Chem. Soc. 1952, 74: 5933

<A NAME="RA50708ST-4B">4b</A> Eppstein SH. Meister PD. Peterson DH. Murray HC. Leigh HM. Lyttle DA. Reineke LM. Weintraub A. J. Am. Chem. Soc. 1953, 75: 408

<A NAME="RA50708ST-5A">5a</A> Wovcha MG. Antosz FJ. Knight JC. Kominek LA. Pyke TR. Biochim. Biophys. Acta 1978, 539: 308

<A NAME="RA50708ST-5B">5b</A> Marsheck WJ. Kraychy S. Muir RD. Appl. Microbiol. 1972, 23: 72

<A NAME="RA50708ST-6A">6a</A> Barton DHR. Motherwell WB. Zard SZ. J. Chem. Soc., Chem. Commun. 1981, 774

<A NAME="RA50708ST-6B">6b</A> Barton DHR. Motherwell WB. Zard SZ. Nouv. J. Chim. 1982, 6: 295

<A NAME="RA50708ST-7A">7a</A> Barton DHR. Motherwell WB. Zard SZ. J. Chem. Soc., Chem. Commun. 1982, 551

<A NAME="RA50708ST-7B">7b</A> Barton DHR. Motherwell WB. Zard SZ. Bull. Soc. Chim. Fr. II 1983, 61

<A NAME="RA50708ST-8A">8a</A> Barton DHR. Zard SZ. J. Chem. Soc., Chem. Commun. 1985, 1098

<A NAME="RA50708ST-8B">8b</A> Barton DHR. Kervagoret J. Zard SZ. Tetrahedron 1990, 46: 7587

<A NAME="RA50708ST-9">9</A> Ono N. Heterocycles 2008, 75: 243

<A NAME="RA50708ST-10A">10a</A> Schöllkopf U. Pure Appl. Chem. 1979, 51: 1347

<A NAME="RA50708ST-10B">10b</A> Schöllkopf U. Angew. Chem. Int. Ed. Engl. 1977, 16: 339

<A NAME="RA50708ST-10C">10c</A> Hoppe D. Angew. Chem. Int. Ed. Engl. 1974, 13: 789

<A NAME="RA50708ST-11A">11a</A> Johnstone RAW. In Mechanisms of Molecular Migrations Vol 2: Thyagarajan BS. John Wiley & Sons; New York: 1969. p.249-266

<A NAME="RA50708ST-11B">11b</A> von Schickh O. Apel G. Padeken H.-G. Scharz HH. Segnitz A. Houben-Weyl: Methoden der Organischen Chemie Vol. X/1: Thieme; Stuttgart: 1971.

<A NAME="RA50708ST-11C">11c</A> 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

<A NAME="RA50708ST-12">12</A> Boivin J. El Kaim L. Kervagoret J. Zard SZ. J. Chem. Soc., Chem. Commun. 1989, 1006

<A NAME="RA50708ST-13">13</A> Alameda-Angulo C. Quiclet-Sire B. Schmidt E. Zard SZ. Org. Lett. 2005, 7: 3489

<A NAME="RA50708ST-14A">14a</A> Barlaam B. Boivin J. El Kaim L. Zard SZ. Tetrahedron Lett. 1991, 32: 623

<A NAME="RA50708ST-14B">14b</A> Boivin J. Barlaam B. El Kaim L. Elton-Farr S. Zard SZ. Tetrahedron 1995, 51: 1675

<A NAME="RA50708ST-15A">15a</A> The configuration at C-14 was later corrected, see: Daniewski AR. J. Org. Chem. 1975, 40: 3127

<A NAME="RA50708ST-15B">15b</A> Daniewski AR. Guzewska M. Kocor M. J. Org. Chem. 1978, 43: 349

<A NAME="RA50708ST-16A">16a</A> Phillips ED. Whitham GH. Tetrahedron Lett. 1993, 34: 2537

<A NAME="RA50708ST-16B">16b</A> Phillips ED. Whitham GH. Tetrahedron Lett. 1993, 34: 2544

<A NAME="RA50708ST-16C">16c</A> Smith TAK. Whitham GH. J. Chem. Soc., Perkin Trans. 1 1989, 313

<A NAME="RA50708ST-16D">16d</A> Smith TAK. Whitham GH. J. Chem. Soc., Perkin Trans. 1 1989, 319

<A NAME="RA50708ST-16E">16e</A> Knight DJ. Lin P. Whitham GH. J. Chem. Soc., Perkin Trans. 1 1987, 2707

<A NAME="RA50708ST-17">17</A> Barlaam B. Boivin J. Zard SZ. Tetrahedron Lett. 1990, 31: 7429

<A NAME="RA50708ST-18">18</A> Alameda-Angulo C. Ph.D. Thesis École Polytechnique; Palaiseau, France: . p.2006

<A NAME="RA50708ST-19A">19a</A> Barton DHR. Motherwell WB. Simon ES. Zard SZ. J. Chem. Soc., Chem. Commun. 1984, 337

<A NAME="RA50708ST-19B">19b</A> Barton DHR. Motherwell WB. Simon ES. Zard SZ.
J. Chem. Soc., Perkin Trans. 1 1986, 2243

<A NAME="RA50708ST-20">20</A> Boivin J. Fouquet E. Zard SZ. Tetrahedron Lett. 1990, 31: 85

<A NAME="RA50708ST-21">21</A> Lamy E. Lüthi P. Paturel C. Winkler T. Jung PMJ. Tetrahedron Lett. 2006, 47: 5657

<A NAME="RA50708ST-22A">22a</A> Lukin KA. Narayanan BA. Tetrahedron 2002, 58: 215

<A NAME="RA50708ST-22B">22b</A> Esteban J. Costa AM. Urpi F. Vilarrasa J. Tetrahedron Lett. 2004, 45: 5563

<A NAME="RA50708ST-23">23</A> Barton DHR. Motherwell WB. Zard SZ. Tetrahedron Lett. 1984, 25: 3707

<A NAME="RA50708ST-24">24</A> Lednicer D. Mitscher LA. The Organic Chemistry of Drug Synthesis Wiley Interscience; New York: 1977.

<A NAME="RA50708ST-25A">25a</A> Laurent H. Wiechert R. In Organic Reactions in Steroid Chemistry Fried J. Edwards JA. Van Nostrand Reinhold; New York: 1972. Chapter 10.

<A NAME="RA50708ST-25B">25b</A> 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

<A NAME="RA50708ST-25C">25c</A> Batres E. Cardenas T. Edwards JA. Monroy G. Mancera O. Djerrassi C. Ringold HJ. J. Org. Chem. 1961, 26: 871

<A NAME="RA50708ST-25D">25d</A> Taub D. Hoffsommer RD. Wendler NL. J. Org. Chem. 1964, 29: 3486

<A NAME="RA50708ST-26">26</A> Boivin J. Chauvet C. Zard SZ. Tetrahedron Lett. 1992, 33: 4913

<A NAME="RA50708ST-27">27</A> Chauvet C. Ph.D. Thesis Université Paris XI; Orsay: France. p.1991

<A NAME="RA50708ST-28">28</A> Barton DHR. Motherwell WB. Wozniak J. Zard SZ. J. Chem. Soc., Perkin Trans. 1 1985, 1865

<A NAME="RA50708ST-29A">29a</A> Barton DHR. Wozniak J. Zard SZ. J. Chem. Soc., Chem. Commun. 1987, 1383

<A NAME="RA50708ST-29B">29b</A> Barton DHR. Wozniak J. Zard SZ. Tetrahedron 1989, 45: 3741

<A NAME="RA50708ST-30">30</A> Van Rheenen V. J. Chem. Soc., Chem. Commun. 1969, 314

<A NAME="RA50708ST-31">31</A> Piatak DM. Wicha J. Chem. Rev. 1978, 78: 199

<A NAME="RA50708ST-32A">32a</A> Boivin J. El Kaim L. Zard SZ. Tetrahedron Lett. 1992, 33: 1285

<A NAME="RA50708ST-32B">32b</A> Boivin J. El Kaim L. Zard SZ. Tetrahedron 1995, 51: 2573

<A NAME="RA50708ST-32C">32c</A> Boivin J. El Kaim L. Zard SZ. Tetrahedron 1995, 51: 2585

<A NAME="RA50708ST-33">33</A> For a review, see: Zard SZ. Org. Biomol. Chem. 2007, 5: 205

<A NAME="RA50708ST-34">34</A> Trimble LA. Street IP. Perrier H. Trembley NM. Weech PK. Bernstein MA. Biochemistry 1993, 32: 12560

<A NAME="RA50708ST-35">35</A> Reeves JT. Gallou F. Song JJ. Tan Z. Lee H. Yee NK. Senanayake CH. Tetrahedron Lett. 2007, 48: 189

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

<A NAME="RA50708ST-37">37</A> El Kaim L. Ph.D. Thesis Université Paris XI; Orsay: France. p.1992

<A NAME="RA50708ST-38">38</A> Boar RB. McGhie JF. Robinson M. Barton DHR. Horwell DC. Stick RV. J. Chem. Soc., Perkin Trans. 1 1975, 1237

<A NAME="RA50708ST-39">39</A> Barton DHR. Zard SZ. J. Chem. Soc., Perkin Trans. 1 1985, 2191

<A NAME="RA50708ST-40">40</A> Laso NM. Quiclet-Sire B. Zard SZ. Tetrahedron Lett. 1996, 37: 1605

<A NAME="RA50708ST-41">41</A> Boar RB. Jetuah FK. McGhie JF. Robinson M. Barton DHR. J. Chem. Soc., Perkin Trans. 1 1977, 2163

<A NAME="RA50708ST-42">42</A> Boivin J. Schiano A.-M. Zard SZ. Tetrahedron Lett. 1992, 33: 7849

<A NAME="RA50708ST-43">43</A> Boivin J. Fouquet E. Zard SZ. Tetrahedron 1994, 50: 1757

<A NAME="RA50708ST-44">44</A> Boivin J. Schiano A.-M. Zard SZ. Zhang H. Tetrahedron Lett. 1999, 40: 4531

<A NAME="RA50708ST-45">45</A> Boivin J. Yousfi M. Zard SZ. Tetrahedron Lett. 1994, 35: 5629

<A NAME="RA50708ST-46">46</A> Cassayre J. Dauge D. Zard SZ. Synlett 2000, 471

<A NAME="RA50708ST-47">47</A> Quiclet-Sire B. Saunier J.-B. Zard SZ. Tetrahedron Lett. 1996, 37: 1397

<A NAME="RA50708ST-48A">48a</A> Cassayre J. Quiclet-Sire B. Saunier J.-B. Zard SZ. Tetrahedron 1998, 54: 1029

<A NAME="RA50708ST-48B">48b</A> Cassayre J. Zard SZ. Synlett 1999, 501

<A NAME="RA50708ST-49">49</A> Cassayre J. Quiclet-Sire B. Saunier J.-B. Zard SZ. Tetrahedron Lett. 1998, 39: 8995

<A NAME="RA50708ST-50">50</A> Boivin J. Yousfi M. Zard SZ. Tetrahedron Lett. 1994, 35: 9553

<A NAME="RA50708ST-51">51</A> Boivin J. Yousfi M. Zard SZ. Tetrahedron Lett. 1997, 38: 5985

<A NAME="RA50708ST-52">52</A> Duncia JV. Piece ME. Santella JB. J. Org. Chem. 1991, 56: 2395

<A NAME="RA50708ST-53">53</A> Boivin J. Husinec S. Zard SZ. Tetrahedron 1995, 51: 11737

<A NAME="RA50708ST-54">54</A> Barton DHR. McCombie SW. J. Chem. Soc., Perkin Trans. 1 1975, 1574

<A NAME="RA50708ST-55">55</A> Quiclet-Sire B. Zard SZ. Tetrahedron Lett. 1998, 39: 9435

<A NAME="RA50708ST-56">56</A> Spassova N. Ph.D. Thesis École Polytechnique; Palaiseau: France. p.2000

<A NAME="RA50708ST-57">57</A> Siddiqui MA. Driscoll JS. Abushanab E. Kelley JA. Barchi JJ. Marquez VE. Nucleosides Nucleotides 2000, 19: 1

For reviews on xanthate transfer chemistry, see:

<A NAME="RA50708ST-58A">58a</A> Zard SZ. Angew. Chem., Int. Ed. Engl. 1997, 36: 672

<A NAME="RA50708ST-58B">58b</A> Zard SZ. In Radicals in Organic Synthesis Vol. 1: Renaud P. Sibi MP. Wiley-VCH; Weinheim: 2001. p.90

<A NAME="RA50708ST-58C">58c</A> Quiclet-Sire B. Zard SZ. Chem. Eur. J. 2006, 12: 6002

<A NAME="RA50708ST-58D">58d</A> Quiclet-Sire B. Zard SZ. Top. Curr. Chem. 2006, 264: 201

<A NAME="RA50708ST-58E">58e</A> See also ref.

For recent reviews, see:

<A NAME="RA50708ST-59A">59a</A> Handbook of RAFT Polymerization Barner-Kowollik C. Wiley-VCH; Weinheim: 2008.

<A NAME="RA50708ST-59B">59b</A> Moad G. Rizzardo E. Thang SH. Aust. J. Chem. 2005, 58: 379

<A NAME="RA50708ST-59C">59c</A> Perrier S. Takolpuckdee T. J. Polym. Sci., Part A: Polym. Chem. 2005, 43: 5347

<A NAME="RA50708ST-60A">60a</A> Georghe A. Quiclet-Sire B. Vila X. Zard SZ. Org. Lett. 2005, 7: 1653

<A NAME="RA50708ST-60B">60b</A> Georghe A. Quiclet-Sire B. Vila X. Zard SZ. Tetrahedron 2007, 63: 7187

<A NAME="RA50708ST-61A">61a</A> Bacqué E. El Qacemi M. Zard SZ. Org. Lett. 2004, 6: 3671

<A NAME="RA50708ST-61B">61b</A> El Qacemi M. Ph.D. Thesis École Polytechnique, Palaiseau; France: 2005.

<A NAME="RA50708ST-62A">62a</A> Ashton MJ. Lawrence C. Karlsson J.-A. Stuttle KAJ. Newton CG. Vacher BYJ. Webber S. Whitnall MJ. J. Med. Chem. 1996, 39: 4888

<A NAME="RA50708ST-62B">62b</A> For a review, see: Brattsand R. Selroos O. In Drugs and Lungs Page CP. Metzger WJ. Raven; New York: 1994. p.101-220

<A NAME="RA50708ST-63">63</A> Quiclet-Sire B. Zard SZ. Tetrahedron Lett. 1998, 39: 1073