Modular Synthesis of Heterocyclic Carbene Precursors Attila Paczal, † Attila C. Be ´nyei, ‡ and Andra ´s Kotschy* ,† Institute of Chemistry, Eo ¨tVo ¨s Lora ´ nd UniVersity, Pa ´ zma ´ ny Pe ´ ter s. 1/A, H-1117 Budapest, Hungary, and Department of Chemistry, Laboratory for X-ray Diffraction, UniVersity of Debrecen, P.O. Box 7, H-4010 Debrecen, Hungary kotschy@chem.elte.hu ReceiVed March 17, 2006 A series of N-heterocyclic carbene precursors, containing an imidazoline or tetrahydropyrimidine framework, were prepared from ω-chloroalkanoyl chlorides. The sequential attachment of nitrogen nucleophiles and subsequent ring closure gave, depending on the reagents used, either the desired dihydroimidazolium and tetrahydropyrimidinium salts or their parent heterocycles. In this latter case, the second substituent was introduced in an alkylation step. The preparation of carbene precursors bearing chiral or bulky substituents was acieved with comparable efficiency. Introduction Following the original reports of O ¨ fele 1 and Wanzlick 2 on the existence of N-heterocyclic carbene (NHC)-metal com- plexes in 1968 and the seminal paper of Arduengo 3 describing stable NHCs, N-heterocyclic carbenes have had a spectacular career in synthetic chemistry, 4 principally as supporting ligands in transition-metal complexes. Such NHC-metal complexes have been successfully utilized in cross-coupling reactions 5 and related processes, including hydrogenation, 6 hydrosilylation, 7 hydroformylation, 8 oxidation, 9 and Pauson-Khand reactions 10 and olefin metathesis, both achiral 11 and enantioselective. 12 Some of the chiral NHC ligands were also successful in other catalytic asymmetric transformations, 13 and besides their role as ligands in metal complexes, certain NHCs also act as efficient organocatalysts. 14 It is thus probably not surprising that the preparation of N-heterocyclic carbene precursors 15,16 and their metal com- plexes 17 has been extensively studied recently. The chemistry of the parent imidazole system and its analogues (oxazoles, triazoles, pyrimidines, and annulated derivatives) is well * To whom correspondence should be addressed. Tel: +36-1-372-2910. Fax: +36-1-372-2909. † Eo ¨tvo ¨s Lora ´nd University. ‡ University of Debrecen. (1) O ¨ fele, K. J. Organomet. Chem. 1968, 12, P4-P43. (2) Wanzlick, H.-W.; Scho ¨nherr, H. J. Angew. Chem., Int. Ed. Engl. 1968, 7, 141-142. (3) Arduengo, A. J.; Harlow, R. L.; Kline, M. J. Am. Chem. Soc. 1991, 113, 361-363. (4) The rapid expansion of the field was greatly facilitated by earlier contributions on stable nonheterocyclic carbenes and their metal complexes. For a comprehensive review of the related literature, see: Bourissou, D.; Guerret, O.; Gabbai, F. P.; Bertrand, G. Chem. ReV. 2000, 100, 39-91. (5) Selected examples include: (a) Bohm, V. P.; Weskamp, T.; Gstott- mayr, C. W.; Herrmann, W. A. Angew. Chem., Int. Ed. 2000, 39, 1602- 1604. (b) Grasa, G. A.; Viciu, M. S.; Huang, J.; Zhang, C.; Trudell, M. L.; Nolan, S. P. Organometallics 2002, 21, 2866-2873. (c) Stauffer, S. R.; Lee, S.; Stambuli, J. P.; Hauck, S. I.; Hartwig, J. F. Org. Lett. 2000, 2, 1423-1426. (6) Perry, M. C.; Cui, X.; Powell, M. T.; Reibenspies, J. H.; Bugess, K. J. Am. Chem. Soc. 2003, 125, 113-123. (7) Enders, D.; Gielen, H. J. Organomet. Chem. 2001, 617-618, 70- 80. (8) Ko ¨ cher, C.; Herrmann, W. A. J. Organomet. Chem. 1997, 532, 261- 265. (9) Jensen, D. R.; Schultz, M. J.; Mueller, J. A.; Sigman, M. S. Angew. Chem., Int. Ed. 2003, 42, 3810-3813. (10) Gibson, S. E.; Johnstone, C.; Loch, J. A.; Steed, J. W.; Stevenazzi, A. Organometallics 2003, 22, 5374-5377. (11) Selected examples include: (a) Trnka, T. M.; Morgan, J. P.; Sanford, M. S.; Wilhelm, T. E.; Scholl, M.; Choi, T.-L.; Ding, S.; Day, M. W.; Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 2546-2558. (b) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2000, 122, 8168-8179. (c) Bujok, R.; Bieniek, M.; Masnyk, M.; Michrowska, A.; Sarosiek, A.; Stepowska, H.; Arlt, D.; Grela, K. J. Org. Chem. 2004, 69, 6894-6896. (d) Wakamatsu, H.; Blechert, S. Angew. Chem., Int. Ed. 2002, 41, 2403-2405. (e) Weskamp, T.; Schattenmann, W. C.; Spiegler, M.; Herrmann, W. A. Angew. Chem., Int. Ed. 1998, 37, 2490-2493. (f) Huang, J.; Stevens, E. D.; Nolan, S. 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