Metalated Indoles, Indazoles, Benzimidazoles, and Azaindoles and Their Synthetic Applications

Hiriyakkanavar Ila; John T. Markiewicz; Vladimir Malakhov; Paul Knochel

doi:10.1055/s-0033-1338501

Synthesis, Inhaltsverzeichnis

Synthesis 2013; 45(17): 2343-2371
DOI: 10.1055/s-0033-1338501

review

Metalated Indoles, Indazoles, Benzimidazoles, and Azaindoles and Their Synthetic Applications

Hiriyakkanavar Ila

^aNew Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 50064, India

,

John T. Markiewicz

^bDepartment Chemie, Ludwig-Maximilians-Universität München, Butenandtstr. 5–13, Haus F, 81377 München, Germany Fax: +49(89)218077680 eMail: paul.knochel@cup.uni-muenchen.de

,

Vladimir Malakhov

^bDepartment Chemie, Ludwig-Maximilians-Universität München, Butenandtstr. 5–13, Haus F, 81377 München, Germany Fax: +49(89)218077680 eMail: paul.knochel@cup.uni-muenchen.de

,

Paul Knochel*

^bDepartment Chemie, Ludwig-Maximilians-Universität München, Butenandtstr. 5–13, Haus F, 81377 München, Germany Fax: +49(89)218077680 eMail: paul.knochel@cup.uni-muenchen.de

› Institutsangaben

Abstract

Alle Artikel dieser Rubrik

Dedicated to Victor Snieckus on the occasion of his 76^th birthday

Abstract

This review focuses on the regioselective metalation of condensed azoles, such as indole, indazole, benzimidazole, 4-, 5-, 6-, and 7-azaindole. The metalation strategies discussed include halogen–metal exchange, metal insertion into carbon–halogen bonds, and directed deprotonation. The influence of different nitrogen-protecting groups and directed metalating groups is discussed. This review covers literature published mainly from 1991 to 2010.

1 Introduction

2 Metalation of Indoles

2.1 C2-Metalation of Indoles

2.2 C3-Metalation of Indoles

2.3 C4–C7-Metalation of Indoles

3 Metalation of Indazoles

4 Metalation of Benzimidazoles

5 Metalation of Azaindoles

6 Conclusion

Key words

metalation - indoles - heterocycles - cross-coupling - natural products

Volltext

Referenzen

References

1a Pozharskii AF, Soldatenkov AT, Katritzky AR In Heterocycles in Life and Society. Wiley-VCH; Weinheim: 1997
1b Ardeo A, Collado MI, Osante I, Ruiz J, Sotomayor N, Lete E. Targets Heterocycl. Syst. 2001; 5: 393
1c Charushin VN, Chupakhin ON. Pure Appl. Chem. 2004; 76: 1621
1d Kirsch G, Hesse S, Comel A. Curr. Org. Synth. 2004; 1: 47

2a Gschward HW, Rodriguez HR. Org. React. 1979; 26: 1
2b Snieckus V. Chem. Rev. 1990; 90: 879
2c Marek I. Chem. Rev. 2000; 100: 2887
2d Knochel P, Millot PJ, Rodriguez AL, Tucker CE. Org. React. 2001; 58: 417
2e Schlosser M. Eur. J. Org. Chem. 2001; 3975
2f Hartung CG, Snieckus V In Modern Arene Chemistry . Astruc D. Wiley-VCH; Weinheim: 2002
2g Schlosser M. Organometallics in Synthesis: A Manual. 2nd ed.; Schlosser M. Wiley; New York: 2002: 1
2h Marek I. Tetrahedron 2002; 58: 9463
2i Clayden J In Selectivity for Synthesis . Baldwin JE, Williams RM. Pergamon/Elsevier Science Ltd; Amsterdam: 2002
2j Leroux F, Schlosser M, Zohar E, Marek I In Chemistry of Organolithium Compounds . Rappoport Z, Marek I. Wiley; New York: 2004. Chapt. 1, 4
2k Leroux F, Jeschke P, Schlosser M. Chem. Rev. 2005; 105: 827
2l Schlosser M. Angew. Chem. Int. Ed. 2005; 44: 376
2m Handbook of Functionalized Organometallics . Knochel P. Wiley-VCH; Weinheim: 2005
2n Hodgson DM, Miles SM. Angew. Chem. Int. Ed. 2006; 45: 935

3 Chen Q, Mollat du Jourdin X, Knochel P. J. Am. Chem. Soc. 2013; 135: 4958

4a Mosrin M, Knochel P. Chem. Eur. J. 2009; 15: 1468
4b Mosrin M, Knochel P. Org. Lett. 2008; 10: 2497

5 Monolikakes SM, Jaric M, Karaghiosoff K, Knochel P. Chem. Commun. 2013; 49: 2124

6a Wunderlich SH, Rohbogner CJ, Unsinn A, Knochel P. Org. Process Res. Dev. 2010; 14: 339
6b Rohbogner CJ, Wirth S, Knochel P. Org. Lett. 2010; 12: 1984

7 Mosrin M, Bresser T, Knochel P. Org. Lett. 2009; 11: 3406

8a Wunderlich S, Knochel P. Chem. Commun. 2008; 6387
8b Mosrin M, Knochel P. Org. Lett. 2009; 11: 1837
8c Crestey F, Knochel P. Synthesis 2010; 1097

9 Despotopoulou C, Klier L, Knochel P. Org. Lett. 2009; 11: 3326
10 Dunst C, Knochel P. J. Org. Chem. 2011; 76: 6972
11 Boudet N, Dubbaka SR, Knochel P. Org. Lett. 2008; 10: 1715
12 Hagg B, Mosrin M, Ila H, Malakhov V, Knochel P. Angew. Chem. Int. Ed. 2011; 50: 9794

13a Mulve RE. Acc. Chem. Res. 2009; 42: 743

14a Joule JA In Science of Synthesis . Vol. 10. Thomas EJ. Georg Thieme Verlag; Stuttgart: 2000. Chapt. 10.13, 361
14b Joule JA, Mills K. Heterocyclic Chemistry . John Wiley and Sons; New York: 2009. Chapt. 20, 373
14c Sundberg RJ. The Chemistry of Indoles . Academic Press; New York: 1970
14d Sundberg RJ. Indoles; 2nd ed.. Academic Press; London: 1996
14e Tyrrell E, Brookes P. Synthesis 2003; 469

15a Cacchi S, Fabrizi G. Chem. Rev. 2005; 105: 2873
15b Rewcastle GW, Katritzky AR. Adv. Heterocycl. Chem. 1993; 56: 155
15c Familoni OB. Synlett 2002; 1181

16a Somei M, Yamada F. Nat. Prod. Rep. 2004; 21: 278
16b Somei M, Yamada F. Nat. Prod. Rep. 2005; 22: 761
16c Horton DA, Bourne GT, Smythe ML. Chem. Rev. 2003; 103: 893 ; and references therein
16d Beller M, Breindl C, Riermeier TH, Tillack A. J. Org. Chem. 2001; 66: 1403 ; and references therein

17a Sundberg RJ. Comprehensive Heterocyclic Chemistry . Vol. 4. Katritzy AR, Rees CW. Peragamon; Oxford: 1984: 313
17b Sundberg RJ. Comprehensive Heterocyclic Chemistry II . Vol. 2. Katritzky AR, Rees CW, Scriven EF. V, Bird CW. Pergamon Press; Oxford: 1996: 119
17c Gribble GW. Comprehensive Heterocyclic Chemistry II . Vol. 2. Katritzky AR, Rees CW, Scriven EF. V, Bird CW. Pergamon Press; Oxford: 1996: 207

18 Baeyer A. Liebigs Ann. Chem. 1866; 140: 295

19a Gribble GW. J. Chem. Soc., Perkin Trans. 1 2000; 1045
19b Gilchrist TL. J. Chem. Soc., Perkin Trans. 1 2001; 2491
19c Humphrey GR, Kuethe JT. Chem. Rev. 2006; 106: 2875
19d Gribble GW. Natural Product Synthesis . Vol. 1. Pearson WH. Jai Press; Greenwich CT: 1990: 43

20 Eisch JJ. Organometallics 2002; 21: 5439

21a Shirley DA, Roussel PA. J. Am. Chem. Soc. 1953; 75: 375
21b See also: Shevchenko NE, Nenajdenko VG, Balenkova ES. Synthesis 2003; 1191

22a Sundberg RJ, Russell HF. J. Org. Chem. 1973; 38: 3324
22b Wahlström N, Stensland B, Bergman J. Synthesis 2004; 1187
22c Kuethe JT, Wong A, Davies IW. Org. Lett. 2003; 5: 3721
22d Wu J.-P, Sanyal S, Lu Z.-H, Senanayake CH. Tetrahedron Lett. 2009; 50: 5667
22e Smart BP, Oslund RC, Walsh LA, Gelb MH. J. Med. Chem. 2006; 49: 2858
22f Mehboobi S, Uecker A, Cénac C, Sellmer A, Eichhorn E, Elz S, Böhmer F.-D, Dove S. Bioorg. Med. Chem. 2007; 15: 2187
22g Naka H, Akagi Y, Yamada K, Imahori T, Kasahara T, Kondo Y. Eur. J. Org. Chem. 2007; 4635

23 Hasan I, Marinelli ER, Lin L.-CC, Fowler FW, Levy AB. J. Org. Chem. 1981; 46: 157
24 Katritzky AR, Akutagawa K. Tetrahedron Lett. 1985; 26: 5935
25 Edwards MP, Doherty AM, Ley SV, Organ HM. Tetrahedron 1986; 42: 3723

26a Hlasta DJ, Bell MR. Heterocycles 1989; 29: 849
26b Katritzky AR, Lue P, Chen YX. J. Org. Chem. 1990; 55: 3688

27a Gmeiner P, Kraxner J, Bollinger B. Synthesis 1996; 1196
27b Kraxner J, Gmeiner P. Synthesis 2000; 1081

28 Gharpure M, Stoller A, Bellamy F, Firnau G, Snieckus V. Synthesis 1991; 1079
29 Takeda Y, Nishiyama H, Ishikura M, Kamata K, Terashima M. Heterocycles 1992; 33: 173

30a Merlic CA, Mclnnes DM, You Y. Tetrahedron Lett. 1997; 38: 6787
30b Ruhland T, Pedersen H, Andersen K. Synthesis 2003; 2236
30c Sakurada J, Satoh T. Tetrahedron 2007; 63: 3806
30d Kusurkar RS, Goswami SK. Tetrahedron 2004; 60: 5315
30e Ishikura M, Kato H, Ohnuki N. Chem. Commun. 2002; 220
30f Bernardo PH, Chai CL. L, Elix JA. Tetrahedron Lett. 2002; 43: 2939
30g Manabe S, Marui Y, Ito Y. Chem. Eur. J. 2003; 9: 1435

31a Kawasaki T, Kodama A, Nishida T, Shimizu K, Somei M. Heterocycles 1991; 32: 221
31b Somei M, Kobayashi T. Heterocycles 1992; 34: 1295

For the N-benzyl protecting group, see ref. 30c and:

31c Sanz R, Ignacio JM, Castroviejo MP, Fańanás FJ. ARKIVOC 2007; (iv): 84

32 Cheng L, Liu L, Sui Y, Wang D, Chen Y.-J. Tetrahedron: Asymmetry 2007; 18: 1833
33 Shirani H, Bergman J, Janosik T. Tetrahedron 2009; 65: 8350
34 Shirani H, Janosik T. J. Org. Chem. 2007; 72: 8984
35 Jiang J, Gribble GW. Tetrahedron Lett. 2002; 43: 4115

36a Bisseret P, Thielges S, Bourg S, Miethke M, Marahiel MA, Eustache J. Tetrahedron Lett. 2007; 48: 6080

For further applications of 2-lithiation of N-Boc-indole, see:

36b So CM, Yeung CC, Lau CP, Kwong FY. J. Org. Chem. 2008; 73: 7803
36c Ishikura M, Takahashi N, Yamada K, Abe T. Heterocycles 2008; 75: 107
36d Bennasar ML, Roca T, Garcia-Diaz D. J. Org. Chem. 2008; 73: 9033

37a Ishikura M, Matsuzaki Y, Agata I. Heterocycles 1997; 45: 2309

For other examples of Suzki coupling and reactions with indolyl-2-boronic acid, see:

37b Vazquez E, Payack JF. Tetrahedron Lett. 2004; 45: 6549
37c de Koning CB, Michael JP, Rousseau A. J. Chem. Soc., Perkin Trans. 1 2000; 1705
37d Johnson CN, Stemp G, Anand N, Stephen SC, Gallagher T. Synlett 1998; 1025
37e Kudo N, Perseghini M, Fu GC. Angew. Chem. Int. Ed. 2006; 45: 1282

38 Vasquez E, Davies IW, Payack JF. J. Org. Chem. 2002; 67: 7551

39a Denmark SE, Baird JD, Regens CS. J. Org. Chem. 2008; 73: 1440
39b Denmark SE, Baird JD. Org. Lett. 2004; 6: 3649
39c Rataboul F, Zapf A, Jackstell R, Harkal S, Riermeier T, Monsees A, Dingerdissen U, Beller M. Chem. Eur. J. 2004; 10: 2983
39d Artemova NV, Chevykalova MN, Luzikov YN, Nifant’ev IE, Nifant’ev EE. Tetrahedron 2004; 60: 10365

40a Bergman J, Venemalm L. J. Org. Chem. 1992; 57: 2495

For further examples of the use of N-lithiocarboxylate as protecting group, see ref. 22b and:

40b Katritzky AR, Le KN. B, Mohapatra PP. Synthesis 2007; 3141
40c Guianvarc’h D, Fourrey J.-L, Dau M.-ET. H, Guérineau V, Benhida R. J. Org. Chem. 2002; 67: 3724
40d Shirani H, Stensland B, Bergman J, Janosik T. Synlett 2006; 2459

41a Hudkins RL, Diebold JL, Marsh FD. J. Org. Chem. 1995; 60: 6218

For other examples of reactions of 2-stannyl indole, see:

41b Labadie SS, Teng E. J. Org. Chem. 1994; 59: 4250
41c Palmisano G, Santagostino M. Helv. Chim. Acta 1993; 76: 2356
41d Dandu R, Tao M, Josef KA, Bacon ER, Hudkins RL. J. Heterocycl. Chem. 2007; 44: 437

42 Fukuda T, Mine Y, Iwao M. Tetrahedron 2001; 57: 975
43 Kondo Y, Yoshida A, Sakamato T. J. Chem. Soc., Perkin Trans. 1 1996; 2331

44a Bresser T, Mosrin M, Monzon G, Knochel P. J. Org. Chem. 2010; 75: 4686
44b Rohbogner CJ, Wunderlich SH, Clososki GC, Knochel P. Eur. J. Org. Chem. 2009; 1781

For further examples of direct 2-zincation of indole, see:

44c L’Helgoual’ch J.-M, Seggio A, Chevallier F, Yonehara M, Jeanneau E, Uchiyama M, Mongin F. J. Org. Chem. 2008; 73: 177

45a Amat M, Llor N, Pshenichnyi G, Bosch J. ARKIVOC 2002; (v): 73
45b Amat M, Hadida S, Pshenichnyi G, Bosch J. J. Org. Chem. 1997; 62: 3158
45c Amat M, Hadida S, Bosch J. Tetrahedron Lett. 1993; 34: 5005

For examples of Negishi cross-coupling of 2-indolylzinc reagents, see:

45d Liu S.-F, Wu Q, Schmider HL, Aziz H, Hu N.-X, Popović Z, Wang S. J. Am. Chem. Soc. 2000; 122: 3671
45e Herz H.-G, Queiroz MJ. R. P, Maas G. Synthesis 1999; 1013

46a Pena MA, Sestelo JP, Sarandeses LA. J. Org. Chem. 2007; 72: 1271
46b Bouissane L, Sestelo JP, Sarandeses LA. Org. Lett. 2009; 11: 1285
46c Naka H, Uchiyama M, Matsumoto Y, Wheatley AE. H, MacPartlin M, Morey JV, Kondo Y. J. Am. Chem. Soc. 2007; 129: 1921

For direct 2-cupration of indole, see:

46d Usui S, Hashimoto Y, Morey JV, Wheatley AE. H, Uchiyama M. J. Am. Chem. Soc. 2007; 129: 15102

47 Palmisano G, Santagostino M. Synlett 1993; 771

48a Whisler MC, MacNeil S, Snieckus V, Beak P. Angew. Chem. Int. Ed. 2004; 43: 2206
48b Mulvey RE, Mongin F, Uchiyama M, Kondo Y. Angew. Chem. Int. Ed. 2007; 46: 3802
48c Milburn RR, Snieckus V. Angew. Chem. Int. Ed. 2004; 43: 888
48d Anctil EJ.-G, Snieckus V. J. Organomet. Chem. 2002; 653: 150
48e Mulvey RE. Organometallics 2006; 25: 1060
48f Veith M, Wieczorek S, Fries K, Huch Z. Anorg. Allg. Chem. 2000; 626: 1237

49a Buttery CD, Jones RG, Knight DW. J. Chem. Soc., Perkin Trans. 1 1993; 1425
49b Buttery CD, Jones RG, Knight DW. Synlett 1991; 315
49c Fisher LE, Labadie SS, Reuter DC, Clark RD. J. Org. Chem. 1995; 60: 6224

50a Gribble GW, Fraser HL, Badenock JC. Chem. Commun. 2001; 805

For further examples of 3-amido as directing group for 2-lithiation of indole, see:

50b Cai X, Snieckus V. Org. Lett. 2004; 6: 2293
50c Gribble GW, Keavy DJ, Davis DA, Saulnier MG, Pelcman B, Barden TC, Sibi MP, Olson ER, BelBruno JJ. J. Org. Chem. 1992; 57: 5878
50d Gribble GW, Jiang J, Liu Y. J. Org. Chem. 2002; 67: 1001

See also the review:

50e Gribble GW, Saulnier MG, Pelkey ET, Kishbaugh TL. S, Liu Y, Jiang J, Trujillo HA, Keavy DJ, Davis DA, Conway SC, Switzer FL, Roy S, Silva RA, Obaza-Nutaitis JA, Sibi MP, Moskalev NV, Barden TC, Chang L, Habeski WM, Pelcman B. Curr. Org. Chem. 2005; 9: 1493

51 James CA, Coelho AL, Gevaert M, Forgione P, Snieckus V. J. Org. Chem. 2009; 74: 4094

52a Abbiati G, Baccalli EM, Marchesini A, Rossi E. Synthesis 2001; 2477

For an earlier example of 2-lithiation of 2-iodoindole, see:

52b Saulnier MG, Gribble GW. J. Org. Chem. 1982; 47: 2810

53a Sun L, Liebeskind LS. Tetrahedron Lett. 1997; 38: 3663
53b Sun L, Liebeskind LS. J. Am. Chem. Soc. 1996; 118: 12473
53c Sun L, Liebeskind LS. J. Org. Chem. 1995; 60: 8194

See also:

53d Fürstner A, Domostoj MM, Scheiper B. J. Am. Chem. Soc. 2006; 128: 8087
53e Gan T, Liu R, Yu P, Zhao S, Cook JM. J. Org. Chem. 1997; 62: 9298

54a Herbert JM, Maggiani M. Synth. Commun. 2001; 31: 947

For other examples of reactions of 2-lithioindole, see:

54b Katritzky AR, Xie L. J. Org. Chem. 1995; 60: 3707
54c Merlic CA, McInnes DM. Tetrahedron Lett. 1997; 38: 7661

55a Kuethe JT, Comins DL. J. Org. Chem. 2004; 69: 2863

For related examples, see:

55b Andersson H, Das S, Gustafsson M, Olsson R, Almqvist F. Tetrahedron Lett. 2010; 51: 4218
55c Barbe G, Pelletier G, Charette AB. Org. Lett. 2009; 11: 3398

56 Kondo Y, Takazawa N, Yoshida A, Sakamoto T. J. Chem. Soc., Perkin Trans. 1 1995; 1207

57a Abarbri M, Thibonnet J, Bérillon L, Dehmel F, Rottländer M, Knochel P. J. Org. Chem. 2000; 65: 4618
57b Baron O, Knochel P. Angew. Chem. Int. Ed. 2005; 44: 3133

58a Yang X, Althammer A, Knochel P. Org. Lett. 2004; 6: 1665
58b Yang X, Knochel P. Synthesis 2006; 2618

59a Conway SC, Gribble GW. Heterocycles 1992; 34: 2095
59b Gribble GW, Allison BD, Conway SC, Saulnier MG. Org. Prep. Proced. Int. 1992; 24: 649
59c Gribble GW, Saulnier MG. J. Org. Chem. 1983; 48: 607
59d Gribble GW, Barden TC. J. Org. Chem. 1985; 50: 5900

60a Liu Y, Gribble GW. Tetrahedron Lett. 2000; 41: 8717
60b Liu Y, Gribble GW. J. Nat. Prod. 2002; 65: 748

61 Liu Y, Gribble GW. Tetrahedron Lett. 2001; 42: 2949

62a Matsuzono M, Fukuda T, Iwao M. Tetrahedron Lett. 2001; 42: 7621. See also ref. 30c

63 Klingebiel U, Luttke W, Noltemeyer M, Schmidt HG. J. Organomet. Chem. 1993; 456: 41

64a Gribble GW, Johnson DA. Tetrahedron Lett. 1987; 28: 5259

For a recent synthesis of semipervirine using the same strategey, see:

64b Lipińska T. Tetrahedron Lett. 2002; 43: 9565

65 Johnson DA, Gribble GW. Heterocycles 1986; 24: 2127

66a Yokoyama Y, Uchida M, Murakami Y. Heterocycles 1989; 29: 1661
66b Zhao Z, Jaworski A, Piel I, Snieckus V. Org. Lett. 2008; 10: 2617

67a Grimaldi T, Romero M, Pujol MD. Synlett 2000; 1788
67b Romero M, Pujol MD. Synlett 2003; 173

68a Comins DL. Synlett 1992; 615
68b Comins DL, Killpack MO. J. Org. Chem. 1987; 52: 104

69 Saulnier MG, Gribble GW. J. Org. Chem. 1982; 47: 757

70a Amat M, Hadida S, Sathyanarayana S, Bosch J. J. Org. Chem. 1994; 59: 10
70b Amat M, Hadida S, Sathyanarayana S, Bosch J. Org. Synth. 1997; 74: 248
70c Amat M, Sathyanarayana S, Hadida S, Bosch J. Heterocycles 1996; 43: 1713
70d Amat M, Hadida S, Bosch J. Tetrahedron Lett. 1994; 35: 793

71a Wynne JH, Stalick WM. J. Org. Chem. 2002; 67: 5850
71b Wynne JH, Stalick WM. J. Org. Chem. 2003; 68: 4845

For further examples of 3-haloindole–lithium exchange, see ref. 40e and:

71c Bernardo PH, Chai CL. L. J. Org. Chem. 2003; 68: 8906
71d Belley M, Scheigetz J, Dubé P, Dolman S. Synlett 2001; 222

72 Qi T, Qiu W, Liu Y, Zhang H, Gao X, Liu Y, Lu K, Du C, Yu G, Zhu D. J. Org. Chem. 2008; 73: 4638

73a Hoerrner RS, Askin D, Volante RP, Reider PJ. Tetrahedron Lett. 1998; 39: 3455

See also:

73b Nishida A, Miyashita N, Fuwa M, Nakagawa M. Heterocycles 2003; 59: 473
73c Li G, Wang E, Chen H, Li H, Liu Y, Wang PG. Tetrahedron 2008; 64: 9033

74 Claridge TD. W, Long JM, Brown JM, Hibbs D, Hursthouse MB. Tetrahedron 1997; 53: 4035 . For an earlier example of the 3-bromoindole bromine–lithium exchange, see ref. 59d
75 Jiang B, Yang C.-G. Heterocycles 2000; 53: 1489
76 Amat M, Seffar F, Llor N, Bosch J. Synthesis 2001; 267

77a Sugiyama H, Yokokawa F, Aoyama T, Shioiri T. Tetrahedron Lett. 2001; 42: 7277
77b Sala DG, Capozzo D, Izzo I, Giordano A, Iommazzo A, Spinella A. Tetrahedron Lett. 2002; 43: 8839

78a Pirrung MC, Li Z, Park K, Zhu J. J. Org. Chem. 2002; 67: 7919
78b Kasahara T, Kondo Y. Chem. Commun. 2006; 891

For an application of 3-indolyl Grignard reagent in the synthesis of grossularine-1, see:

78c Choshi T, Yamada S, Sugino E, Kuwada T, Hibino S. J. Org. Chem. 1995; 60: 5899

79 Liu Y, Gribble GW. Tetrahedron Lett. 2002; 43: 7135
80 Ueda I, Nishiura M, Takahashi T, Eda K, Hashimoto M, Yamamura K. Tetrahedron Lett. 2006; 47: 8535

81a Staubitz A, Dohle W, Knochel P. Synthesis 2003; 233
81b Kneisel FF, Knochel P. Synlett 2002; 1799
81c Gommermann N, Koradin C, Knochel P. Synthesis 2002; 2143
81d Jensen AE, Dohle W, Sapountzis I, Lindsay DM, Vu VA, Knochel P. Synthesis 2002; 565
81e Krasovsky A, Knochel P. Angew. Chem. Int. Ed. 2004; 43: 3333

82a Sapountzis I, Knochel P. Angew. Chem. Int. Ed. 2004; 43: 897

For an earlier example of halogen–magnesium exchange with ethylmagnesium bromide, see:

82b Kondo Y, Yoshida A, Sato S, Sakamoto T. Heterocycles 1996; 42: 105

83a Sapountzis I, Lin W, Kofink CC, Despotopoulou C, Knochel P. Angew. Chem. Int. Ed. 2005; 44: 1654

For a 3-magnesium–zinc exchange in indole, see:

83b Korn TJ, Knochel P. Synlett 2005; 1185

For a 3-magnesium–tin exchange:

83c Mal SK, Bohé L, Achab S. Tetrahedron 2008; 64: 5904
83d Tricotet T, O’Shea DF. Chem. Eur. J. 2010; 16: 6678

84 Manolikakes G, Knochel P. Angew. Chem. Int. Ed. 2009; 48: 205

85a Sakamato T, Kondo Y, Takazawa N, Yamanaka H. Tetrahedron Lett. 1993; 34: 5955

See also:

85b Prasad AS. B, Stevenson TM, Citineni JR, Nyzam V, Knochel P. Tetrahedron 1997; 53: 7237
85c Gong L.-Z, Knochel P. Synlett 2005; 267

86a Metzger A, Piller FM, Knochel P. Chem. Commun. 2008; 5824
86b Piller FM, Appukkuttan P, Gavryushin A, Helm M, Knochel P. Angew. Chem. Int. Ed. 2008; 47: 6802
86c Piller FM. Metzger A, Schade MA, Haag BA, Gavryushin A, Knochel P. Chem. Eur. J. 2009; 15: 7192
86d Blümke T, Piller FM, Knochel P. Chem. Commun. 2010; 4082

87 Shade MA, Manolikakes G, Knochel P. Org. Lett. 2010; 12: 3648

88a Fukuda T, Maeda R, Iwao M. Tetrahedron 1999; 55: 9151
88b Iwao M, Kuraishi T. Heterocycles 1992; 34: 1031

For a recent example of the N-DEB directing group in 7-lithiation, see:

88c Okada M, Sato I, Cho SJ, Suzuki Y, Ojika M, Dubnau D, Sakagami Y. Biosci. Biotechnol. Biochem. 2004; 68: 2374

89 Hartung CG, Fecher A, Chapell B, Snieckus V. Org. Lett. 2003; 5: 1899
90 Masters NF, Mathews N, Nechvatal G, Widdowson DA. Tetrahedron 1989; 45: 5955
91 Dickens MJ, Mowlem TJ, Widdowson DA, Slawin AM. Z, Williams DJ. J. Chem. Soc., Perkin Trans. 1 1992; 323

92a Fukuda T, Akashima H, Iwao M. Tetrahedron 2005; 61: 6886 ; and references therein
92b See also: Nagakawa K, Somei M. Heterocycles 1994; 39: 31

93 Iwao M. Heterocycles 1993; 36: 29

94a Shinohara H, Fukuda T, Iwao M. Tetrahedron 1999; 55: 10989
94b Iwao M, Ishibashi F. Tetrahedron 1997; 53: 51

95a Iwao M, Motoi O, Fukuda T, Ishibashi F. Tetrahedron 1998; 54: 8999
95b Moro-oka Y, Fukuda T, Iwao M. Tetrahedron Lett. 1999; 40: 1713

96a Meseguer B, Alonso-Díaz D, Griebenow N, Herget T, Waldmann H. Angew. Chem. Int. Ed. 1999; 38: 2902
96b Meseguer B, Alonso-Diaz D, Griebenow N, Herget T, Waldmann H. Chem. Eur. J. 2000; 6: 3943

97 Hayakawa Y, Singh M, Shibata N, Takeuchi Y, Kirk KL. J. Fluorine Chem. 1999; 97: 161
98 Iwao M, Motoi O. Tetrahedron Lett. 1995; 36: 5929
99 Pérez-Serrano L, Casarrubios L, Domínguez G, Freire G, Pérez-Castells J. Tetrahedron 2002; 58: 5407
100 Hurt CR, Lin R, Rapoport H. J. Org. Chem. 1999; 64: 225
101 Chauder B, Larkin A, Snieckus V. Org. Lett. 2002; 4: 815

102a Griffen EJ, Roe DG, Snieckus V. J. Org. Chem. 1995; 60: 1484
102b Kinsman AC, Snieckus V. Tetrahedron Lett. 1999; 40: 2453
102c Rousseau J.-F, Dodd RH. Heterocycles 2001; 55: 2289
102d Tois J, Koskinen A. Tetrahedron Lett. 2003; 44: 2093

103 Moro-oka Y, Iwakiri S, Fukuda T, Iwao M. Tetrahedron Lett. 2000; 41: 5225

104a Schlosser M, Ginanneschi A, Leroux F. Eur. J. Org. Chem. 2006; 2956
104b Schlosser M. Angew. Chem. Int. Ed. 2006; 45: 5432

105a Moyer MP, Shiurba JF, Rapoport H. J. Org. Chem. 1986; 51: 5106
105b Yang Y, Martin AR, Nelson DL, Regan J. Heterocycles 1992; 34: 1169
105c Takami H, Koshimura H, Kumazawa T. Heterocycles 1999; 51: 1119

106 Cherry K, Lebegue N, Leclerc V, Carato P, Yous S, Berthelot P. Tetrahedron Lett. 2007; 48: 5751

107a Feldman KS, Eastman KJ, Lessene G. Org. Lett. 2002; 4: 3525
107b Balle T, Andersen K, Vedsø P. Synthesis 2002; 1509

108a Li L, Martins A. Tetrahedron Lett. 2003; 44: 689
108b Li L, Martins A. Tetrahedron Lett. 2003; 44: 5987

109a Buszek KR, Luo D, Kondrashov M, Brown N, Vander Velde D. Org. Lett. 2007; 9: 4135
109b Brown N, Luo D, Vander Velde D, Yang S, Brassfield A, Buszek KR. Tetrahedron Lett. 2009; 50: 63
109c Brown N, Luo D, Decapo JA, Buszek KR. Tetrahedron Lett. 2009; 50: 7113
109d Buszek KR, Brown N, Luo D. Org. Lett. 2009; 11: 201

110 Andersson H, Banchelin TS.-L, Das S, Gustafsson M, Olsson R, Almqvist F. Org. Lett. 2010; 12: 284

Reviews:

111a Stadlbauer W In Science of Synthesis . Vol. 12. Neier R. Georg Thieme Verlag; Stuttgart: 2002. Chapt. 12.2, 227
111b Elguero J In Comprehensive Heterocyclic Chemistry II . Vol. 3. Katritzky AR, Rees CW, Scriven EF. S. Pergamon; Oxford: 1996: 1
111c Elguero J In Comprehensive Heterocyclic Chemistry . Vol. 5. Katritzky AR, Rees CW. Peragamon; Oxford: 1984: 167

Recent reviews:

112a Schmidt A, Beutler A, Snovydovych B. Eur. J. Org. Chem. 2008; 4073

For biological activity of indazole derivatives, see:

112b Cerecetto H, Gerpe A, González M, Arán VJ, de Ocáriz CO. Mini-Rev. Med. Chem. 2005; 5: 869

113a Collot V, Varlet D, Rault S. Tetrahedron Lett. 2000; 41: 4363
113b Collot V, Bovy PR, Rault S. Tetrahedron Lett. 2000; 41: 9053
113c Arnautu A, Collot V, Ros JC, Alayrac C, Witulski B, Rault S. Tetrahedron Lett. 2002; 43: 2695

114a Welch WM, Hanau CE, Whalen WM. Synthesis 1992; 937

See also:

114b Frasca AR. Tetrahedron Lett. 1962; 3: 1115
114c Casey ML, Kemp DS, Paul KG, Cox DD. J. Org. Chem. 1973; 38: 2294

115 Yang X, Knochel P. Synlett 2004; 2303
116 Luo G, Chen L, Dubowchik G. J. Org. Chem. 2006; 71: 5392
117 Bunnell A, O’Yang C, Petrica A, Soth MJ. Synth. Commun. 2006; 36: 285
118 Danielson ME, Hays DS, Kshirsagar TA, Haraldson CA, Lundquist GD, Wurst JR, Lindstrom KJ, Mackey SS, Willie DJ, Heppner PD, Leir CM, Benson KE. J. Org. Chem. 2007; 72: 4570
119 Despotopoulou C, Gignoux C, McConnell D, Knochel P. Synthesis 2009; 3661

120a Grimmett MR In Science of Synthesis . Vol. 12. Neier R. Georg Thieme Verlag; Stuttgart: 2002. Chapt. 12.4; 52
120b Grimmett MR In Comprehensive Heterocyclic Chemistry II . Vol. 3. Katritzky AR, Rees CW, Scriven EF. S. Elsvier; Oxford: 1996: 77
120c Grimmett MR In Comprehensive Heterocyclic Chemistry . Vol. 5. Katritzky AR, Rees CW. Pergamon; Oxford: 1984: 345
120d Grimmett MR. Imidazoles and Benzimidazole Synthesis, In Best Synthetic Methods. Meth-Cohn O. Academic Press; London: 1997

121 Ooi HC, Suschitzky H. J. Chem. Soc., Perkin Trans. 1 1982; 2871
122 Katritzky AR, Akutagawa K. J. Org. Chem. 1989; 54: 2949
123 Carr AA, Hay DA, Kane JM, Staeger MA. J. Org. Chem. 1990; 55: 1399
124 Katritzky AR, Ramer WH, Lam JN. J. Chem. Soc., Perkin Trans. 1 1987; 775

125a Katritzky AR, Rewcastle GW, Fan W.-Q. J. Org. Chem. 1988; 53: 5685
125b Kuzmenko VV, Filatova TA, Pozharskic AF. Chem. Heterocycl. Comp. (Engl. Transl.) 1992; 28: 1009

126 Katritzky AR, Drewniak-Deyrup M, Lan X, Brunner F. J. Heterocycl. Chem. 1989; 26: 829
127 Hilf C, Bosold F, Harms K, Marsch M, Boche G. Chem. Ber./Recl. 1997; 130: 1213
128 Rivas FM, Giessert AJ, Diver ST. J. Org. Chem. 2002; 67: 1708
129 Wunderlich SH, Kienle M, Knochel P. Angew. Chem. Int. Ed. 2009; 48: 7256
130 Asakawa K.-i, Dannenberg JJ, Fitch KJ, Hall SS, Kadowaki C, Karady S, Kii S, Maeda K, Marcune BF, Mase T, Miller RA, Reamer RA, Tschaen DM. Tetrahedron Lett. 2005; 46: 5081
131 Park SB, Alper H. Org. Lett. 2003; 5: 3209
132 Walker SR, Carter EJ, Belinda CH, Morris JC. Chem. Rev. 2009; 109: 3080

133a Hetherington WM, Micheils RH, Eisenthal KL. Chem. Phys. Lett. 1979; 66: 230
133b Herbich J, Sepiol J, Waluk J. J. Mol. Struct. 1984; 114: 329
133c Wu Q, Esteghamatian M, Hu N, Popovic ZD, Enright G, Beeze SR, Wang S. Angew. Chem. Int. Ed. 1999; 38: 985 ; and references therein

For reviews on 4-,5-,6-azaindole, see:

134a Popowycz F, Mérour J.-Y, Joseph B. Tetrahedron 2007; 63: 8689
134b Le Hyaric M, Vieira de Almeida M, Nora de Souza MV. Quim. Nova 2002; 25: 1165
134c Song JJ, Reeves JT, Gallou F, Tan Z, Yee NK, Senanayake CH. Chem. Soc. Rev. 2007; 36: 1120
134d Review on 7-azaindole: Popowycz F, Routier S, Joseph B, Mérour J.-Y. Tetrahedron 2007; 63: 1031

135 Bisagni E, Chi Hung N, Lhoste JM. Tetrahedron 1983; 39: 1777
136 Dormoy J.-R, Heymes A. Tetrahedron 1993; 49: 2885
137 Praly-Deprez I, Rivalle C, Belehradek J, Huel C, Bisagni E. J. Chem. Soc., Perkin Trans. 1 1991; 3173
138 Lefoix M, Daillant J.-P, Routier S, Mérour J.-Y, Gillaizeau I, Couder G. Synthesis 2005; 3581
139 Kelly TA, McNeil DW, Rose JM, David E, Shih C.-K, Grob PM. J. Med. Chem. 1997; 40: 2430
140 Mahboobi S, Pongratz H, Hufsky H, Hockemeyer J, Frieser M, Lyssenko A, Paper DH, Bürgermeister J, Böhmer F.-D, Fiebig H.-H, Burger AM, Baasner S, Beckers T. J. Med. Chem. 2001; 44: 4535
141 Bracher F, Hildebrand D. Tetrahedron 1994; 50: 12329
142 Desarbre E, Coudret S, Meheust C, Mérour J.-Y. Tetrahedron 1997; 53: 3637

143a Álvarez M, Fernández D, Joule JA. Tetrahedron Lett. 2001; 42: 315
143b Ahaidar A, Fernández D, Danelón G, Cuevas C, Manzanares I, Albericio F, Joule JA, Álvarez M. J. Org. Chem. 2003; 68: 10020

144 Curtis NR, Kulagowski JJ, Leeson PD, Ridgill MP, Emms F, Freedman SB, Patel S, Patel S. Bioorg. Med. Chem. Lett. 1999; 9: 585
145 Mouaddib A, Joseph B, Hasnaoui A, Mérour J.-Y. Tetrahedron Lett. 1999; 40: 5853
146 Alvarez M, Fernández D, Joule JA. Synthesis 1999; 615

147a Kuo GH, Prouty C, DeAngelis A, Shen L, O’Neill DJ, Shah C, Connolly PJ, Murray WV, Conway BR, Cheung P, Westover L, Xu JZ, Look RA, Demarest KT, Emanuel S, Middleton SA, Jolliffe L, Beavers MP, Chen X. J. Med. Chem. 2003; 46: 4021
147b Kumar A, Say M, Boykin DW. Synthesis 2008; 707

148 Thibault C, L’Heureux A, Bhide RS, Ruel R. Org. Lett. 2003; 5: 5023
149 L’Heureux A, Thibault C, Ruel R. Tetrahedron Lett. 2004; 45: 2317