Synthesis of Polyalkylated Indoles Using a Thallium(III)-Mediated Ring-Contraction Reaction

Abstract

A new approach to the synthesis of cyclopenta[g]indole derivatives possessing structural features of natural alkaloids, such as trikentrins and herbindols, is described. The key step in the sequence is a thallium(III)-mediated ring-contraction reaction to transform a cyclohexene moiety into a functionalized cyclopentyl unit.

cyclopenta[g]indoles - thallium trinitrate - ring contraction

References

For some examples concerning the isolation of C2-C3 fused cycloalkylindoles, see:

<A NAME="RM03007SS-1A">1a</A> Ondeyka JG. Helms GL. Hensens OD. Goetz MA. Zink DL. Tsipouras A. Shoop WL. Slayton L. Dombrowski AW. Polishook JD. Ostlind DA. Tsou NN. Ball RG. Singh SB. J. Am. Chem. Soc.  1997,  119:  8809 

<A NAME="RM03007SS-1B">1b</A> Kato L. Braga RM. Koch I. Kinoshita LS. Phytochemistry  2002,  60:  315 

<A NAME="RM03007SS-1C">1c</A> Singh SB. Ondeyka JG. Jayasuriya H. Zink DL. Ha SN. Dahl-Roshak A. Greene J. Kim JA. Smith MM. Shoop W. Tkacz JS. J. Nat. Prod.  2004,  67:  1496 

<A NAME="RM03007SS-1D">1d</A> Carrol AR. Hyde E. Smith J. Quinn RJ. Guymer G. Forster PI. J. Org. Chem.  2005,  70:  1096 

For some examples concerning the synthesis of C2-C3 fused cycloalkylindoles, see:

<A NAME="RM03007SS-2A">2a</A> Giannini G. Marzi M. Moretti GP. Penco S. Tinti MO. Pesci S. Lazzaro F. De Angelis F. Eur. J. Org. Chem.  2004,  2411 

<A NAME="RM03007SS-2B">2b</A> Maertens F. Van den Bogaert A. Compernolle F. Hoornaert GJ. Eur. J. Org. Chem.  2004,  4648 

<A NAME="RM03007SS-2C">2c</A> Smith AB. Kurti L. Davulcu AH. Org. Lett.  2006,  8:  2167 

<A NAME="RM03007SS-2D">2d</A> Sturino CF. Lachance N. Boyd M. Berthelette C. Labelle M. Li L. Roy B. Scheigetz J. Tsou N. Brideau C. Cauchon E. Carriere M.-C. Denis D. Greig G. Kargman S. Lamontagne S. Mathieu M.-C. Sawyer N. Slipetz D. O’Neill G. Wang Z. Zamboni R. Metters KM. Young RN. Bioorg. Med. Chem. Lett.  2006,  16:  3043 

<A NAME="RM03007SS-3A">3a</A> Capon RJ. MacLeod JK. Scammels PJ. Tetrahedron  1986,  42:  6545 

<A NAME="RM03007SS-3B">3b</A> Herb R. Carrol AR. Yoshida WY. Scheuer PJ. Paul VJ. Tetrahedron  1990,  46:  3089 

<A NAME="RM03007SS-4">4</A> Sawyer JS. Beight DW. Smith ECR. Snyder DW. Chastain MK. Tielkin RL. Hartley LW. Carlson DG. J. Med. Chem.  2005,  48:  893 

<A NAME="RM03007SS-5A">5a</A> MacLeod JK. Monahan LC. Tetrahedron Lett.  1988,  29:  391 

<A NAME="RM03007SS-5B">5b</A> Muratake H. Natsume M. Tetrahedron Lett.  1989,  30:  5771 

<A NAME="RM03007SS-5C">5c</A> Muratake H. Watanabe M. Goto K. Natsume M. Tetrahedron  1990,  46:  4179 

<A NAME="RM03007SS-5D">5d</A> MacLeod JK. Monahan LC. Aust. J. Chem.  1990,  43:  329 

<A NAME="RM03007SS-5E">5e</A> Boger DL. Zhang M. J. Am. Chem. Soc.  1991,  113:  4230 

<A NAME="RM03007SS-5F">5f</A> Muratake H. Mikawa A. Natsume M. Tetrahedron Lett.  1992,  33:  4595 

<A NAME="RM03007SS-5G">5g</A> Muratake H. Seino T. Natsume M. Tetrahedron Lett.  1993,  34:  4815 

<A NAME="RM03007SS-5H">5h</A> Wiedenau P. Monse B. Blechert S. Tetrahedron  1995,  51:  1167 

<A NAME="RM03007SS-5I">5i</A> MacLeod JK. Ward A. Willis AC. Aust. J. Chem.  1998,  51:  177 

<A NAME="RM03007SS-5J">5j</A> Jackson SK. Banfield SC. Kerr MA. Org. Lett.  2005,  7:  1215 

<A NAME="RM03007SS-5K">5k</A> Huntley RJ. Funk RL. Org. Lett.  2006,  8:  3403 

<A NAME="RM03007SS-5L">5l</A> Jackson SK. Kerr MA. J. Org. Chem.  2007,  72:  1405 

For some reviews concerning thallium(III) in organic synthesis, see:

<A NAME="RM03007SS-6A">6a</A> McKillop A. Taylor EC. In Comprehensive Organometallic Chemistry   Vol. 7:  Wilkinson G. Pergamon Press; New York: 1982.  p.465 

<A NAME="RM03007SS-6B">6b</A> Ferraz HMC. Silva LF. Vieira TO. Synthesis  1999,  2001 

<A NAME="RM03007SS-6C">6c</A> Uemura S. In Synthetic Reagents   Vol. 5:  Pizey JS. Ellis Horwood; Chichester: 1983.  p.164 

For some examples of rearrangement of olefins with TTN, see:

<A NAME="RM03007SS-7A">7a</A> McKillop A. Hunt JD. Taylor EC. Kienzle F. Tetrahedron Lett.  1970,  11:  5275 

<A NAME="RM03007SS-7B">7b</A> McKillop A. Hunt JD. Kienzle F. Bigham E. Taylor EC. J. Am. Chem. Soc.  1973,  95:  3635 

<A NAME="RM03007SS-7C">7c</A> Taylor EC. Chiang C.-S. McKillop A. White JF. J. Am. Chem. Soc.  1976,  98:  6750 

<A NAME="RM03007SS-7D">7d</A> Rigby JH. Pigge FC. J. Org. Chem.  1995,  60:  7392 

<A NAME="RM03007SS-7E">7e</A> Rigby JH. Pigge FC. Synlett  1996,  631 

<A NAME="RM03007SS-7F">7f</A> Butkus E. Zilinskas A. Stoncius S. Rozembergas R. Urbanová M. Setnicka V. Boui P. Volka K. Tetrahedron: Asymmetry  2002,  13:  633 

<A NAME="RM03007SS-7G">7g</A> Singh OV. Muthukrishnan M. Sundaravedivelu M. Synth. Commun.  2006,  36:  946 

<A NAME="RM03007SS-8A">8a</A> Ferraz HMC. Silva LF. Vieira TO. Tetrahedron  2001,  57:  1709 

<A NAME="RM03007SS-8B">8b</A> Ferraz HMC. Aguilar AM. Silva LF. Tetrahedron  2003,  59:  5817 

<A NAME="RM03007SS-8C">8c</A> Silva LF. Sousa RMF. Ferraz HMC. Aguilar AM. J. Braz. Chem. Soc.  2005,  16:  1160 

<A NAME="RM03007SS-8D">8d</A> Silva LF. Quintiliano SAP. Craveiro MV. Vieira FYM. Ferraz HMC. Synthesis  2007,  355 

<A NAME="RM03007SS-8E">8e</A> For a related reaction using iodine(III), see: Silva LF. Siqueira FA. Pedrozo EC. Vieira FYM. Doriguetto AC. Org. Lett.  2007,  9:  1433 

<A NAME="RM03007SS-9A">9a</A> Somei M. Hasegawa T. Kaneko C. Heterocycles  1983,  20:  1983 

<A NAME="RM03007SS-9B">9b</A> Somei M. Saida Y. Funamoto T. Ohta T. Chem. Pharm. Bull.  1987,  35:  3146 

<A NAME="RM03007SS-9C">9c</A> Banerji A. Nandi G. Heterocycles  1987,  26:  1221 

<A NAME="RM03007SS-9D">9d</A> Tholander J. Bergman J. Tetrahedron  1999,  55:  12595 

<A NAME="RM03007SS-10">10</A> Desarbre E. Savelon L. Cornec O. Mérour JY. Tetrahedron  1996,  52:  2983 

<A NAME="RM03007SS-11">11</A>

The X-ray crystal structure data have been deposited at the Cambridge Crystallographic Data Centre and allocated the deposition number CCDC 656449. Copies of the data can be obtained free of charge on application to The Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (Fax: + 44 1223 336 033; e-mail: [e-mail]).

<A NAME="RM03007SS-12A">12a</A> Anderson CB. Winstein S. J. Org. Chem.  1963,  28:  605 

<A NAME="RM03007SS-12B">12b</A> Abley P. Byrd JE. Halpern J. J. Am. Chem. Soc.  1973,  95:  2591 

<A NAME="RM03007SS-13">13</A> Zhang M. Schuster GB. J. Am. Chem. Soc.  1994,  116:  4852 

<A NAME="RM03007SS-14">14</A> Bartoli G. Palmieri G. Bosco M. Dalpozzo R. Tetrahedron Lett.  1989,  30:  2129 

<A NAME="RM03007SS-15">15</A> Michael JP. Nkwelo MM. Tetrahedron  1990,  46:  2549 

<A NAME="RM03007SS-16">16</A>

A complex mixture was obtained when 9 was treated with 1.1 equiv of TTN in MeOH at 0 °C.

<A NAME="RM03007SS-17">17</A> Ghren L. Ragnarsson U. Angew. Chem. Int. Ed.  1984,  23:  296 

<A NAME="RM03007SS-18">18</A> Ottoni O. Cruz R. Alves R. Tetrahedron  1998,  54:  13915 

<A NAME="RM03007SS-19A">19a</A> Lee JB. Price MJ. Tetrahedron  1964,  20:  1017 

<A NAME="RM03007SS-19B">19b</A> Sekizaki H. Ito M. Inoue S. Bull. Chem. Soc. Jpn.  1978,  51:  2439 

<A NAME="RM03007SS-20">20</A> Seyferth D. Org. Synth. Coll. Vol. 4   Wiley; New York: 1963.  p.258