On the Dual Role of N-Heterocyclic Carbenes as Bases and Nucleophiles in Reactions with Organic Halides

Abstract

The synthetic consequences of different basicities, nucleophilicities, and sterics of N-heterocyclic carbenes have been studied in reactions of imidazolin-2-ylidenes with organic halides. Highly nucleophilic and less basic carbenes cleanly gave alkyli­deneimidazolines, the deoxy analogues of Breslow-type intermediates. More basic NHCs engaged in unwanted deprotonation or dehydrohalogenation reactions.

Key words

N-heterocyclic carbenes - enamines - umpolung - imidazoles - nucleophilicity

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11

See Supporting Information for further details on the reaction of 3k with n-BuLi.

12

Basicity determinations of NHCs have been performed by deprotonation of fluorene systems. See: refs. 4b,e.

15

Similar, but even more pronounced bond orders were reported for related 1,3-dimethylimidazolin-2-ylidene acetophenone. See ref. 9g.

19

All structures were optimized at the B3LYP/6-31G* density functional level of theory and the optimized structures were further characterized as energy minimum structures without imaginary frequencies at the same level by frequency calculations, which provide further zero-point energies and thermal correction to enthalpy and Gibbs free energy at 298 K. Thermal energy corrections at B3LYP/6-31G* from the frequency calculations have been added to the final Gibbs free energies for analyzing the substitution effects. Furthermore, we have also tested single-point energy calculations at the B3LYP/6-311+G* level on B3LYP/6-31G* optimized geometries. Since both B3LYP/6-311+G* and B3LYP/6-31G* gave approximately the same results for the exchange reactions, we used only the B3LYP/6-31G* Gibbs free energy for discussion and comparison. All calculations have been carried out by using the Gaussian 03 program package: Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A. Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, Rev. C.02, Gaussian, Inc., Wallingford CT, 2004.

24

Crystal structure data of compounds 4c and 6 are available under CCDC 837921 and 837922 from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/conts/retrieving.html.