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 Pines SH.
Org. Process Res. Dev.
2004,
8:
708
4a Peterson DH.
Murray HC.
Eppstein SH.
Reineke LM.
Weintraub A.
Meister PD.
Leigh HM.
J.
Am. Chem. Soc.
1952,
74:
5933
4b Eppstein SH.
Meister
PD.
Peterson DH.
Murray HC.
Leigh HM.
Lyttle DA.
Reineke LM.
Weintraub A.
J. Am. Chem. Soc.
1953,
75:
408
5a Wovcha MG.
Antosz FJ.
Knight JC.
Kominek
LA.
Pyke TR.
Biochim.
Biophys. Acta
1978,
539:
308
5b Marsheck WJ.
Kraychy S.
Muir RD.
Appl. Microbiol.
1972,
23:
72
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
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
9 Ono N.
Heterocycles
2008,
75:
243
10a Schöllkopf U.
Pure Appl. Chem.
1979,
51:
1347
10b Schöllkopf U.
Angew. Chem. Int. Ed. Engl.
1977,
16:
339
10c Hoppe D.
Angew.
Chem. Int. Ed. Engl.
1974,
13:
789
11a Johnstone RAW. In
Mechanisms of Molecular Migrations
Vol
2:
Thyagarajan BS.
John
Wiley & Sons;
New York:
1969.
p.249-266
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.
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
13 Alameda-Angulo C.
Quiclet-Sire B.
Schmidt E.
Zard
SZ.
Org. Lett.
2005,
7:
3489
14a Barlaam B.
Boivin J.
El Kaim L.
Zard SZ.
Tetrahedron
Lett.
1991,
32:
623
14b Boivin J.
Barlaam B.
El Kaim L.
Elton-Farr S.
Zard SZ.
Tetrahedron
1995,
51:
1675
15a Daniewski AR.
J. Org. Chem.
1975,
40:
3127
15b Daniewski AR.
Guzewska M.
Kocor M.
J. Org. Chem.
1978,
43:
349
16a Phillips ED.
Whitham GH.
Tetrahedron Lett.
1993,
34:
2537
16b Phillips ED.
Whitham GH.
Tetrahedron Lett.
1993,
34:
2544
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
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.
20 Boivin J.
Fouquet E.
Zard SZ.
Tetrahedron
Lett.
1990,
31:
85
21 Lamy E.
Lüthi P.
Paturel C.
Winkler T.
Jung PMJ.
Tetrahedron Lett.
2006,
47:
5657
22a Lukin KA.
Narayanan BA.
Tetrahedron
2002,
58:
215
22b Esteban J.
Costa AM.
Urpi F.
Vilarrasa J.
Tetrahedron Lett.
2004,
45:
5563
23 Barton DHR.
Motherwell WB.
Zard SZ.
Tetrahedron Lett.
1984,
25:
3707
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
25c Batres E.
Cardenas T.
Edwards JA.
Monroy G.
Mancera O.
Djerrassi C.
Ringold HJ.
J.
Org. Chem.
1961,
26:
871
25d Taub D.
Hoffsommer
RD.
Wendler NL.
J. Org. Chem.
1964,
29:
3486
26 Boivin J.
Chauvet C.
Zard SZ.
Tetrahedron
Lett.
1992,
33:
4913
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
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
30 Van Rheenen V.
J.
Chem. Soc., Chem. Commun.
1969,
314
31 Piatak DM.
Wicha J.
Chem. Rev.
1978,
78:
199
32a Boivin J.
El Kaim L.
Zard SZ.
Tetrahedron Lett.
1992,
33:
1285
32b Boivin J.
El Kaim L.
Zard SZ.
Tetrahedron
1995,
51:
2573
32c Boivin J.
El Kaim L.
Zard SZ.
Tetrahedron
1995,
51:
2585
33 Zard SZ.
Org. Biomol. Chem.
2007,
5:
205
34 Trimble LA.
Street IP.
Perrier H.
Trembley NM.
Weech PK.
Bernstein MA.
Biochemistry
1993,
32:
12560
35 Reeves JT.
Gallou F.
Song JJ.
Tan Z.
Lee H.
Yee NK.
Senanayake CH.
Tetrahedron
Lett.
2007,
48:
189
36 Quiclet-Sire, B.; Zard, S. Z. unpublished
results.
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
39 Barton DHR.
Zard SZ.
J.
Chem. Soc., Perkin Trans. 1
1985,
2191
40 Laso NM.
Quiclet-Sire B.
Zard SZ.
Tetrahedron
Lett.
1996,
37:
1605
41 Boar RB.
Jetuah FK.
McGhie JF.
Robinson M.
Barton DHR.
J. Chem. Soc., Perkin Trans.
1
1977,
2163
42 Boivin J.
Schiano A.-M.
Zard SZ.
Tetrahedron
Lett.
1992,
33:
7849
43 Boivin J.
Fouquet E.
Zard SZ.
Tetrahedron
1994,
50:
1757
44 Boivin J.
Schiano A.-M.
Zard SZ.
Zhang H.
Tetrahedron Lett.
1999,
40:
4531
45 Boivin J.
Yousfi M.
Zard SZ.
Tetrahedron
Lett.
1994,
35:
5629
46 Cassayre J.
Dauge D.
Zard SZ.
Synlett
2000,
471
47 Quiclet-Sire B.
Saunier J.-B.
Zard SZ.
Tetrahedron
Lett.
1996,
37:
1397
48a Cassayre J.
Quiclet-Sire B.
Saunier J.-B.
Zard SZ.
Tetrahedron
1998,
54:
1029
48b Cassayre J.
Zard SZ.
Synlett
1999,
501
49 Cassayre J.
Quiclet-Sire B.
Saunier J.-B.
Zard SZ.
Tetrahedron Lett.
1998,
39:
8995
50 Boivin J.
Yousfi M.
Zard SZ.
Tetrahedron
Lett.
1994,
35:
9553
51 Boivin J.
Yousfi M.
Zard SZ.
Tetrahedron
Lett.
1997,
38:
5985
52 Duncia JV.
Piece ME.
Santella JB.
J. Org. Chem.
1991,
56:
2395
53 Boivin J.
Husinec S.
Zard SZ.
Tetrahedron
1995,
51:
11737
54 Barton DHR.
McCombie SW.
J.
Chem. Soc., Perkin Trans. 1
1975,
1574
55 Quiclet-Sire B.
Zard SZ.
Tetrahedron Lett.
1998,
39:
9435
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
58a Zard
SZ.
Angew. Chem., Int. Ed. Engl.
1997,
36:
672
58b Zard SZ. In
Radicals in Organic
Synthesis
Vol. 1:
Renaud P.
Sibi MP.
Wiley-VCH;
Weinheim:
2001.
p.90
58c Quiclet-Sire B.
Zard SZ.
Chem. Eur. J.
2006,
12:
6002
58d Quiclet-Sire B.
Zard SZ.
Top. Curr. Chem.
2006,
264:
201
58e
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
59c Perrier S.
Takolpuckdee T.
J. Polym. Sci., Part A:
Polym. Chem.
2005,
43:
5347
60a Georghe A.
Quiclet-Sire B.
Vila X.
Zard SZ.
Org. Lett.
2005,
7:
1653
60b Georghe A.
Quiclet-Sire B.
Vila X.
Zard SZ.
Tetrahedron
2007,
63:
7187
61a Bacqué E.
El Qacemi M.
Zard SZ.
Org.
Lett.
2004,
6:
3671
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
62b 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
