Synthesis of Bi- and Tricyclic α,β-Unsaturated Lactams as Potential Michael Acceptors Starting from Heterocyclic Imines

Abstract

New α,β-unsaturated valerolactams showing potential as Michael acceptors were synthesized from heterocyclic imines as starting materials. The synthetic procedure is based on an acid chloride addition in the first step, followed by a modified Hosomi-Sakurai­ reaction, and a final ring-closing metathesis using a ruthenium catalyst.

heterocycles - imines - unsaturated lactams - Michael acceptor - ring-closing metathesis

References

<A NAME="RT14708SS-1A">1a</A> Navickiene HMD. Alecio AC. Kato MJ. Bolzani VD. Young MCM. Cavalheiro AJ. Furlan M. Phytochemistry  2000,  55:  621 

<A NAME="RT14708SS-1B">1b</A> Chen JJ. Chang YL. Teng CM. Su CC. Chen IS. Planta Med.  2002,  68:  790 

<A NAME="RT14708SS-1C">1c</A> Chen JJ. Duh CY. Huang HY. Chen IS. Helv. Chim. Acta  2003,  86:  2058 

<A NAME="RT14708SS-1D">1d</A> Tsai IL. Lee FP. Wu CC. Duh CY. Ishikawa T. Chen JJ. Chen YC. Seki H. Chen IS. Planta Med.  2005,  71:  535 

<A NAME="RT14708SS-1E">1e</A> Cardona W. Quinones W. Robledo S. Velez ID. Murga J. Garcia-Fortanet J. Carda M. Cardona D. Echeverri F. Tetrahedron  2006,  62:  4086 

<A NAME="RT14708SS-1F">1f</A> Ding PL. Liao ZX. Huang H. Zhou P. Chen DF. Bioorg. Med. Chem. Lett.  2006,  16:  1231 

<A NAME="RT14708SS-2A">2a</A> Sundberg RJ. Bukowick PA. Holcombe FO. J. Org. Chem.  1967,  32:  2938 

<A NAME="RT14708SS-2B">2b</A> Hua DH. Zhang F. Chen J. J. Org. Chem.  1994,  59:  5084 

<A NAME="RT14708SS-2C">2c</A> Amat M. Pérez M. Llor N. Bosch J. Org. Lett.  2002,  4:  2787 

<A NAME="RT14708SS-2D">2d</A> Chandra KL. Chandrasekhar M. Singh VK. J. Org. Chem.  2002,  67:  4630 

<A NAME="RT14708SS-2E">2e</A> Fuwa H. Kaneko A. Sugimoto Y. Tomita T. Iwatsubo T. Saski M. Heterocycles  2006,  70:  101 

<A NAME="RT14708SS-2F">2f</A> Maio DG. Tardella PA. Gazz. Chim. Ital.  1964,  94:  590 

<A NAME="RT14708SS-3A">3a</A> Flemming A. Br. J. Exp. Pathol.  1929,  10:  226 

<A NAME="RT14708SS-3B">3b</A> Penicilline (C), In Römpp Online V. 3.1   Thieme; Stuttgart: 2008. RD-16-00773

<A NAME="RT14708SS-3C">3c</A> Dalhoff A. Infection  1979,  7:  294 

<A NAME="RT14708SS-3D">3d</A> Holzgrabe U. Pharm. Unserer Zeit  2006,  35:  410 

<A NAME="RT14708SS-4A">4a</A> Gillies PS. Dunn CJ. Drugs  2000,  60:  333 

<A NAME="RT14708SS-4B">4b</A> Lohray BB. Bhusan V. Rao BP. Medhavan GR. Murali N. Rao KN. Reddy AK. Rajesh BM. Reddy PG. Chakrabarti R. Vikramadithyan RK. Rajagopalan R. Mamidi RNVS. Jajoo HK. Subramanian S. J. Med. Chem.  1998,  41:  1619 

<A NAME="RT14708SS-5">5</A> Elander RP. Appl. Microbiol. Biotech.  2003,  61:  385 

<A NAME="RT14708SS-6A">6a</A> Matsumoto Y. Tsuzuki R. Matsuhisa A. Takayama K. Yoden T. Uchida W. Asano M. Fujita S. Yanagisawa I. Fujikura T. Chem. Pharm. Bull.  1996,  44:  103 

<A NAME="RT14708SS-6B">6b</A> Kobayashi T. Strobeck M. Schwartz A. Mori Y. Eur. J. Pharmacol.  1997,  332:  313 

<A NAME="RT14708SS-6C">6c</A> Matsumoto Y. Tsuzuki R. Matsuhisa A. Yoden T. Yamagiwa Y. Yanagisawa I. Shibanuma T. Nohira H. Bioorg. Med. Chem.  2000,  8:  393 

<A NAME="RT14708SS-6D">6d</A> Okuyama K. Kiuchi S. Okamoto M. Narita H. Kudo Y. Eur. J. Pharmacol.  2000,  398:  209 

<A NAME="RT14708SS-6E">6e</A> Cecchetti V. Calderone V. Tabarrini O. Sabatini S. Filipponi E. Testai L. Spogli R. Martinotti E. Fravolini A. J. Med. Chem.  2003,  46:  3670 

<A NAME="RT14708SS-7A">7a</A> Trapani G. Reho A. Morlacchi F. Latrofa A. Marchini P. Venturi F. Cantalamessa F. Farmaco, Ed. Sci.  1985,  40:  369 

<A NAME="RT14708SS-7B">7b</A> Armenise D. Trapani G. Stasi F. Morlacchi F. Arch. Pharm. (Weinheim, Ger.)  1998,  331:  54 

<A NAME="RT14708SS-8A">8a</A> Hayakawa I. Atarashi S. Yokohama S. Imamura M. Sakano K. Furukawa M. Antimicrob. Agents Chemother.  1986,  29:  163 

<A NAME="RT14708SS-8B">8b</A> Atarashi S. Tsurumi H. Fujiwara T. Hayakawa I. J. Heterocycl. Chem.  1991,  28:  329 

<A NAME="RT14708SS-8C">8c</A> Hirata T. Saito H. Tomioka H. Sato K. Jidoi J. Hosoe K. Hidaka T. Antimicrob. Agents Chemother.  1995,  39:  2295 

<A NAME="RT14708SS-9">9</A> Martens J. Offermanns H. Scherberich P. Angew. Chem., Int. Ed. Engl.  1981,  20:  668 ; Angew. Chem. 1981, 93, 680

<A NAME="RT14708SS-10">10</A> Weber M. Jakob J. Martens J. Liebigs Ann. Chem.  1992,  1 

<A NAME="RT14708SS-11">11</A> Gröger H. Martens J. Sulf. Lett.  1996,  19:  197 

<A NAME="RT14708SS-12">12</A> Watzke M. Schulz K. Johannes K. Ullrich P. Martens J. Eur. J. Org. Chem.  2008,  3859 

<A NAME="RT14708SS-13">13</A> Böhme H. Hartke K. Chem. Ber.  1963,  96:  600 

<A NAME="RT14708SS-14">14</A> Schwarze W. Drauz K. Martens J. Chem.-Ztg.  1987,  111:  149 

<A NAME="RT14708SS-15">15</A> Hosomi A. Sakurai H. Tetrahedron Lett.  1976,  1295 

<A NAME="RT14708SS-16A">16a</A> Hart DJ. Tsai Y.-M. Tetrahedron Lett.  1981,  22:  1567 

<A NAME="RT14708SS-16B">16b</A> Kraus GA. Neuenschwander K. J. Chem. Soc., Chem. Commun.  1982,  134 

<A NAME="RT14708SS-16C">16c</A> Kano S. Yuasa Y. Shibuya S. Heterocycles  1987,  26:  373 

<A NAME="RT14708SS-16D">16d</A> Herborn C. Zietlow A. Steckhan E. Angew. Chem., Int. Ed. Engl.  1989,  28:  1399 ; Angew. Chem. 1989, 101, 1392

<A NAME="RT14708SS-17A">17a</A> Rodriguez S. Castillo E. Carda M. Marco JA. Tetrahedron  2002,  58:  1185 

<A NAME="RT14708SS-17B">17b</A> Chen Y. Zhang H. Nan F. J. Comb. Chem.  2004,  6:  684 

<A NAME="RT14708SS-17C">17c</A> Deiters A. Pettersson M. Martin SF. J. Org. Chem.  2006,  71:  6547 

<A NAME="RT14708SS-17D">17d</A> Liu G. Tai W.-Y. Li Y.-L. Nan F.-J. Tetrahedron Lett.  2006,  47:  3295 

<A NAME="RT14708SS-17E">17e</A> Fiorelli C. Savoia D. J. Org. Chem.  2007,  72:  6022 

<A NAME="RT14708SS-18">18</A>

In former investigations using similar substrates, a first-generation Grubbs catalyst showed less activity.^¹²

<A NAME="RT14708SS-19">19</A>

CCDC 706274 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.