Synthesis of 2,2"-Biscarbazoles by Reductive Biaryl Coupling [1]

Abstract

The first reductive biaryl coupling of carbazoles is presented, along with the synthesis of the appropriately halogenated coupling substrates. A completely regioselective halogenation of carbazoles was achieved applying the DoM (Directed ortho-Metalation) strategy with different combinations of directing groups. In the course of the evaluation of a suitable method for benzylic oxidations of carbazolic alcohols, a new protocol using the hypervalent iodine reagent BTIB was established.

Key words

biscarbazole - directed ortho-metalation - reductive biaryl coupling - Ullmann reaction - hypervalent iodine

References

• 1 Novel Concepts in Directed Biaryl Synthesis, part 97; for part 96, see: Bringmann G. Menche D. Acc. Chem. Res.  2001,  34:  615 
• 2a Chakraborty DP. In The Alkaloids   Vol. 44:  Brossi A. Academic Press; New York: 1993.  p.257 
• 2b Furukawa H. Trends Heterocycl. Chem.  1993,  3:  185 
• 2c Ito C. Thoyama Y. Omura M. Kajiura I. Furukawa H. Chem. Pharm. Bull.  1993,  41:  2096 
• 3 Bringmann G. Günther C. Ochse M. Schupp O. Tasler S. In Progress in the Chemistry of Organic Natural Products   Vol. 82:  Herz W. Falk H. Kirby GW. Moore RE. Tamm C. Springer; Wien: 2001. 
• 4 For the recent atropo-selective synthesis of as yet unnatural analogs of biscarbazole alkaloids involving a "redox-neutral" Pd-catalyzed intramolecular biaryl coupling, see: Bringmann G. Tasler S. Endress H. Mühlbacher J. Chem. Commun.  2001,  761 
• 5 Bringmann G. Tasler S. Tetrahedron  2001,  57:  331 
• 6 Bouaziz Z. Nebois P. Poumaroux A. Fillion H. Heterocycles  2000,  52:  977 
• 7a Bringmann G. Ledermann A. Stahl M. Gulden K.-P. Tetrahedron  1995,  51:  9353 
• 7b Lin G. Zhang A. Tetrahedron  2000,  56:  7163 
• 8 Bringmann G. Tasler S. Endress H. Kraus J. Messer K. Wohlfarth M. Lobin W. J. Am. Chem. Soc.  2001,  123:  2703 
• 9 For a coincidental preparation of the 2,2"-biscarbazole core as a minor side product using CuCl₂, see: Murphy WS. Bertrand M. J. Chem. Soc., Perkin Trans. 1  1998,  4115 
• 10 Sainsbury M. Tetrahedron  1980,  36:  3327 
• 11 Fanta PE. Synthesis  1974,  9 
• 12a Bringmann G. Walter R. Weirich R. Angew. Chem. Int. Ed. Engl.  1990,  29:  977 
• 12b Dai D. Martin OR. J. Org. Chem.  1998,  63:  7628 
• 13 Knight DW. In Comprehensive Organic Synthesis   Vol. 3:  Trost BM. Fleming I. Pergamon Press; Oxford: 1991.  p.481 
• 14 Meyers AI. J. Heterocycl. Chem.  1998,  35:  991 
• 15 Bringmann G. Hinrichs J. Pabst T. Henschel P. Peters K. Peters E.-M. Synthesis  2001,  155 
• 16a Bringmann G. Walter R. Weirich R. In Methods of Organic Chemistry (Houben Weyl)   4th ed., Vol. E21a:  Helmchen G. Hoffmann RW. Mulzer J. Schaumann E. Thieme; Stuttgart: 1995.  p.567 
• 16b Miyano S. Fukushima H. Handa S. Ito H. Hashimoto H. Bull. Chem. Soc. Jpn.  1988,  61:  3249 
• 16c Takahashi M. Kuroda T. Ogiku T. Ohmizu H. Kondo K. Iwasaki T. Heterocycles  1993,  36:  1867 
• 17 Snieckus V. Chem. Rev.  1990,  90:  879 
• 18 Bringmann G. Tasler S. Endress H. Peters K. Peters E.-M. Synthesis  1998,  1501 
• 19 Bringmann G. Tasler S. Tetrahedron  2001,  57:  2337 
• 20 For a preparation of MOMCl avoiding carcinogenic impurities, see: Amato JS. Karady S. Sletzinger M. Weinstock LM. Synthesis  1979,  970 
• 23a Winkle MR. Ronald RC. J. Org. Chem.  1982,  47:  2101 
• 23b Ronald RC. Winkle MR. Tetrahedron  1983,  39:  2031 
• 23c Coutts SJ. Wallace TW. Tetrahedron  1994,  50:  11755 
• The methyl group of N-methylcarbazoles can only be removed enzymatically or under harsh conditions:
• 24a Miyata N. Kiuchi H. Hirobe M. Chem. Pharm. Bull.  1981,  29:  1489 
• 24b Yang W. Jiang T. Acosta D. Davis PJ. Xenobiotica  1993,  23:  973 
• 24c Moskalev NV. Sirotkina EE. Chem. Heterocycl. Compd.  1987,  23:  275 
• 24d Buu-Hoi NP. Saint-Ruf G. J. Chem. Soc. (C)  1966,  924 
• 24e Cadogan JIG. Hutchison HS. McNab H. Tetrahedron  1992,  48:  7747 
• 25 Bennetau B. Mortier J. Moyroud J. Guesnet J.-L. J. Chem. Soc., Perkin Trans. 1  1995,  1265 
• 26 Comins DL. Brown JD. J. Org. Chem.  1989,  54:  3730 
• 27 Chakraborty DP. Chowdhury BK. J. Org. Chem.  1968,  33:  1265 
• 28 Zhang G.-S. Shi Q.-Z. Chen M.-F. Cai K. Synth. Commun.  1997,  27:  3691 
• For related oxidations of alcohols to aldehydes, see:
• 29a Spyroudis S. Varvoglis A. Synthesis  1975,  445 
• 29b Narasaka K. Morikawa A. Saigo K. Mukaiyama T. Bull. Chem. Soc. Jpn.  1977,  50:  2773 
• 29c Müller P. Godoy J. Tetrahedron Lett.  1981,  22:  2361 
• 29d Müller P. Godoy J. Helv. Chim. Acta  1983,  66:  1790 
• 29e De Mico A. Margarita R. Parlanti L. Vescovi A. Piancatelli G. J. Org. Chem.  1997,  62:  6974 
• 30a Dess DB. Martin JC. J. Org. Chem.  1983,  48:  4155 
• 30b Speicher A. Bomm V. Eichler T. J. Prakt. Chem.  1996,  338:  588 
• 30c Dess DB. Martin JC. J. Am. Chem. Soc.  1991,  113:  7277 
• 30d Frigerio M. Santagostino M. Sputore S. J. Org. Chem.  1999,  64:  4537 
• 31 Wipf P. Jung J.-K. Rodriguez S. Lazo JS. Tetrahedron  2001,  57:  283 
• 32a Takada T. Arisawa M. Gyoten M. Hamada R. Tohma H. Kita Y. J. Org. Chem.  1998,  63:  7698 
• 32b Arisawa M. Utsumi S. Nakajima M. Ramesh NG. Tohma H. Kita Y. Chem. Commun.  1999,  469 
• 32c Tohma H. Morioka H. Takizawa S. Arisawa M. Kita Y. Tetrahedron  2001,  57:  345 
• 33 Omura K. Swern D. Tetrahedron  1978,  34:  1651 
• 34a Choshi T. Sada T. Fujimoto H. Nagayama C. Sugino E. Hibino S. J. Org. Chem.  1997,  62:  2535 
• 34b Rigby JH. Wilson JZ. Tetrahedron Lett.  1984,  25:  1429 
• 35a Lindgren BO. Nilsson T. Acta Chem. Scand.  1973,  27:  888 
• 35b Colombo L. Gennari C. Santandrea M. Narisano E. Scolastico C. J. Chem. Soc., Perkin Trans. 1  1980,  136 
• 36 Neises B. Steglich W. Angew. Chem. Int. Ed. Engl.  1978,  17:  522 
• 37a Fuson RC. Cleveland EA. In Org. Synth.   Coll. Vol. 3:  Horning EC. Wiley; New York: 1955.  p.339 
• 37b Kleiderer EC. Adams R. J. Am. Chem. Soc.  1933,  55:  4219 
• 38a Kobayashi S. Mineo S. Kihara M. Tagashira S. Chem. Pharm. Bull.  1976,  24:  2191 
• 38b Takahashi M. Ogiku T. Okamura K. Da-te T. Ohmizu H. Kondo K. Iwasaki T. J. Chem. Soc., Perkin Trans. 1  1993,  1473 
• 39 Dallacker F. Leidig H. Chem. Ber.  1979,  112:  2672 
• 40 Zhang S. Zhang D. Liebeskind LS. J. Org. Chem.  1997,  62:  2312 
• 41a Lipshutz BH. Müller P. Leinweber D. Tetrahedron Lett.  1999,  40:  3677 
• 41b Nicolaou KC. Chu X.-J. Ramanjulu JM. Natarajan S. Bräse S. Rübsam F. Boddy CNC. Angew. Chem. Int. Ed. Engl.  1997,  36:  1539 
• 41c Escudero S. Perez D. Guitian E. Castedo L. Tetrahedron Lett.  1997,  38:  5375 
• 41d Iyoda M. Otsuka H. Sato K. Nisato N. Oda M. Bull. Chem. Soc. Jpn.  1990,  63:  80 
• 41e Semmelhack MF. Helquist P. Jones LD. Keller L. Mendelson L. Ryono LS. Smith JG. Stauffer RD. J. Am. Chem. Soc.  1981,  103:  6460 
• 41f Bringmann G. Hinrichs J. Peters K. Peters E.-M. J. Org. Chem.  2001,  66:  629 
• 42 Bringmann G. Hinrichs J. Henschel P. Peters K. Peters E.-M. Synlett  2000,  1822 
• 43a Hassan J. Penalva V. Lavenot L. Gozzi C. Lemaire M. Tetrahedron  1998,  54:  13793 
• 43b Hennings DD. Iwama T. Rawal VH. Org. Lett.  1999,  1:  1205 
• 44a Lipshutz BH. Kayser F. Liu Z.-P. Angew. Chem. Int. Ed. Engl.  1994,  33:  1842 
• 44b For a related coupling, see: Sugimura T. Yamada H. Inoue S. Tai A. Tetrahedron: Asymmetry  1997,  8:  649 
• 45a Lin G.-Q. Zhong M. Tetrahedron: Asymmetry  1997,  8:  1369 
• 45b Kyasnoor RV. Sargent MV. Chem. Commun.  1998,  2713 
• 46a Bringmann G. Hinrichs J. Tetrahedron: Asymmetry  1997,  8:  4121 
• 46b Bringmann G. Hinrichs J. Kraus J. Wuzik A. Schulz T. J. Org. Chem.  2000,  65:  2517 
• 47a Bringmann G. Breuning M. Tasler S. Synthesis  1999,  525 
• 47b Bringmann G. Tasler S. In Current Trends in Organic Synthesis   Scolastico C. Nicotra F. Kluwer Academic / Plenum Publishers; New York: 1999.  p.105 
• 48 Peters K. Peters E.-M. Tasler S. Endress H. Bringmann G. Z. Kristallogr  2001,  216:  119 
• 49 Chakraborty DP. Barman BK. Bose PK. Tetrahedron  1965,  21:  681 

21

Some details of the synthesis of 2-halogenated carbazoles have already been part of a preliminary communication: see reference 3.

22

LiAlH₄ reduction led to complete reduction to give a 3-methyl group, see reference 17.