Abstract
Halogens, in particular fluorine atoms, are favorite tools to fine-tune the chemical and biological properties of pharmaceutical or agricultural development products. At the same time, such an electronegative substituent can effectively assist the site-selective functionalization of an aromatic or heterocyclic core compound by directing a metal to the targeted position, the metal acting as a harbinger for the definitive substituent. The concept is illustrated by typical examples selected from the carbazole, indole, pyrrole, pyrazole, imidazole, pyridine, quinoline and pyrimidine fields.
1 Introduction
2 Carbazoles and Indoles
3 Pyrroles, Pyrazoles and Imidazoles
4 Pyridines, Quinolines and Pyrimidines
5 Conclusions and Outlook
Key Words
fluorine - functionalization - halogens - organometallic reagents - organic synthesis - regioselectivity
References
1
Comprehensive Medicinal Chemistry
Vol. 1-6:
Hansch C.
Sammes PG.
Taylor JB.
Colin J.
Emmett JC.
Kennewell PD.
Ramsden CA.
Pergamon Press;
Oxford:
1990.
2
Garner P.
Kaniskan HU.
Hu JY.
Youngs WJ.
Panzner M.
Org. Lett.
2006,
8:
3647
3
Bleicher KH.
Nettekoven M.
Peters JU.
Wyler R.
Chimia
2004,
58:
588
4
Lipinski CA.
Lombardo F.
Dominy BW.
Feeney PJ.
Adv. Drug Del. Rev.
1997,
23:
3 ; Chem. Abstr . 1997 , 126 , 162025
5
Schlosser M. In Organometallics in Synthesis: A Manual
Vol. 2:
Schlosser M.
Wiley;
Chichester:
2002.
p.1-352
6
Gilman H.
Kirby RH.
J. Org. Chem.
1936,
1:
146
7
Gilman H.
Gray S.
J. Org. Chem.
1958,
23:
1476
8
Katritzky AR.
Rewcastle GW.
Demiguel LMV.
J. Org. Chem.
1988,
53:
794
9
Shirley DA.
Roussel PA.
J. Am. Chem. Soc.
1953,
75:
375
10
Ziegler FE.
Spitzner EB.
J. Am. Chem. Soc.
1970,
92:
3492
11
Sundberg RJ.
Russell HF.
J. Org. Chem.
1973,
38:
3324
12
Hasan I.
Marinelli ER.
Lin LCC.
Fowler FW.
Levy AB.
J. Org. Chem.
1981,
46:
157
13
Hlasta DJ.
Bell MR.
Heterocycles
1989,
29:
849
14
Katritzky AR.
Lue P.
Chen YX.
J. Org. Chem.
1990,
55:
3688
15
Sundberg RJ.
Parton RL.
J. Org. Chem.
1976,
41:
163
16
Schlosser M.
Angew. Chem. Int. Ed.
2005,
44:
376 ; Angew. Chem. 2005 , 117 , 380
17
Schlosser M.
Ginanneschi A.
Leroux F.
Eur. J. Org. Chem.
2006,
2956
18 Leroux, F.; Ginanneschi, A.; Schlosser, M. unpublished results, 2005 .
19
Shirley DA.
Gross BH.
Roussel PA.
J. Org. Chem.
1955,
20:
225
20
Gjøs N.
Gronowitz S.
Acta Chem. Scand.
1971,
25:
2596
21
Wrackmeyer B.
Nöth H.
Chem. Ber.
1976,
109:
1075
22
Muchowski JM.
Solas DR.
J. Org. Chem.
1984,
49:
203
23
Faigl F.
Schlosser M.
Tetrahedron
1993,
49:
10271
24
Chen W.
Stephenson EK.
Cava MP.
Jackson YA.
Org. Synth.
1992,
70:
151
25
Muchowski JM.
Naef R.
Helv. Chim. Acta
1984,
67:
1168
26
Kozikowski AP.
Cheng XM.
J. Org. Chem.
1984,
49:
3239
27
Nguyên DL.
Schlosser M.
Helv. Chim. Acta
1977,
60:
2085
28
Schick JW.
Hartough HD.
J. Am. Chem. Soc.
1948,
70:
286
29
Schlosser M.
Volle J.-N.
Leroux F.
Schenk K.
Eur. J. Org. Chem.
2002,
2913
30
Shirley DA.
Alley PW.
J. Am. Chem. Soc.
1957,
79:
4922
31
Roe AM.
J. Chem. Soc.
1963,
2195
32
Whitten JP.
Matthews DP.
Mccarthy JR.
J. Org. Chem.
1986,
51:
1891
33
Tertov BA.
Burykin VV.
Sadekov ID.
Khim. Geterotsikl. Soedin.
1969,
560 ; Chem. Abstr. 1969 , 71 , 124328
34
Noyce DS.
Stowe GT.
Wong W.
J. Org. Chem.
1974,
39:
2301
35
Iddon B.
Heterocycles
1985,
23:
417
36
Iddon B.
Khan N.
J. Chem. Soc., Perkin Trans. 1
1987,
1453
37
Iddon B.
Khan N.
Lim BL.
J. Chem. Soc., Perkin Trans. 1
1987,
1457
38
Lipshutz BH.
Hagen W.
Tetrahedron Lett.
1992,
33:
5865
39
Groziak MP.
Wei LL.
J. Org. Chem.
1992,
57:
3776
40
Gribble GW.
Saulnier MG.
Tetrahedron Lett.
1980,
21:
4137
41
Gribble GW.
Saulnier MG.
Heterocycles
1993,
35:
151
42
Marsais F.
Bréant P.
Ginguène A.
Quéguiner G.
J. Organomet. Chem.
1981,
216:
139
43
Marsais F.
Laperdrix B.
Güngör T.
Mallet M.
Quéguiner G.
J. Chem. Res., Synop.
1982,
278
44
Choppin S.
Gros P.
Fort Y.
Org. Lett.
2000,
2:
803
45
Choppin S.
Gros P.
Fort Y.
Eur. J. Org. Chem.
2001,
603
46
Bobbio C.
Schlosser M.
J. Org. Chem.
2005,
70:
3039
47
Marzi E.
Bobbio C.
Cottet F.
Schlosser M.
Eur. J. Org. Chem.
2005,
2116
48
Cottet F.
Marull M.
Lefebvre O.
Schlosser M.
Eur. J. Org. Chem.
2003,
1559
49
Schlosser M.
Marull M.
Eur. J. Org. Chem.
2003,
1569
50
Schlosser M.
Mongin F.
Chem. Soc. Rev.
2007,
36:
1161
51
Katsoulos G.
Takagishi S.
Schlosser M.
Synlett
1991,
731
52
Mongin F.
Maggi R.
Schlosser M.
Chimia
1996,
50:
650
53
Marzi E.
Bigi A.
Schlosser M.
Eur. J. Org. Chem.
2001,
1371
54
Radinov R.
Haimova M.
Simova E.
Synthesis
1986,
886
55
Radinov R.
Chanev C.
Haimova M.
J. Org. Chem.
1991,
56:
4793
56
Gu YG.
Bayburt EK.
Tetrahedron Lett.
1996,
37:
2565
57
Cale AD.
Gero TW.
Walker KR.
Lo YS.
Welstead WJ.
Jaques LW.
Johnson AF.
Leonard CA.
Nolan JC.
Johnson DN.
J. Med. Chem.
1989,
32:
2178
58
Bobbio C.
Rausis T.
Schlosser M.
Chem. Eur. J.
2005,
11:
1903
59
Schlosser M.
Rausis T.
Eur. J. Org. Chem.
2004,
1018
60
Coe PL.
Stuart AM.
Moody DJ.
J. Fluorine Chem.
1998,
92:
27
61
Hatanaka Y.
Hiyama T.
Synlett
1991,
845
62
Cottet F.
Schlosser M.
Eur. J. Org. Chem.
2004,
3793
63
Cottet F.
Marull M.
Mongin F.
Espinosa D.
Schlosser M.
Synthesis
2004,
1619
64
Schlosser M.
Heiss C.
Eur. J. Org. Chem.
2003,
4618
65
Marzi E.
Gorecka J.
Schlosser M.
Synthesis
2004,
1609
66
Comins DL.
Hong H.
Saha JK.
Gao JH.
J. Org. Chem.
1994,
59:
5120
67
Quéguiner G.
Marsais F.
Snieckus V.
Epsztajn J.
Adv. Heterocycl. Chem.
1991,
52:
187
68
Marsais F.
Bouley E.
Quéguiner G.
J. Organomet. Chem.
1979,
171:
273
69
Shi G.-q.
Takagishi S.
Schlosser M.
Tetrahedron
1994,
50:
1129
70
Caubère P.
Chem. Rev.
1993,
93:
2317
71
Gros P.
Fort Y.
Quéguiner G.
Caubère P.
Tetrahedron Lett.
1995,
36:
4791
72
Marull M.
Schlosser M.
Eur. J. Org. Chem.
2003,
1576
73
Lefebvre O.
Marull M.
Schlosser M.
Eur. J. Org. Chem.
2003,
2115
74
Marull M.
Lefebvre O.
Schlosser M.
Eur. J. Org. Chem.
2004,
54
75
Langley BW.
J. Am. Chem. Soc.
1956,
78:
2136
76
Sandosham J.
Undheim K.
Tetrahedron
1994,
50:
275
77
Schlosser M.
Lefebvre O.
Ondi L.
Eur. J. Org. Chem.
2006,
1593
78
Plé N.
Turck A.
Martin P.
Barbey S.
Quéguiner G.
Tetrahedron Lett.
1993,
34:
1605
79
Plé N.
Turck A.
Heynderickx A.
Quéguiner G.
J. Heterocycl. Chem.
1994,
31:
1311
80
Plé N.
Turck A.
Heynderickx A.
Quéguiner G.
J. Heterocycl. Chem.
1997,
34:
551