ORGANIC
LETTERS
2009
Vol. 11, No. 16
3710-3713
One-Pot Synthesis of Unsymmetrical
N-Heterocyclic Carbene Ligands from
N-(2-Iodoethyl)arylamine Salts
B. A. Bhanu Prasad and Scott R. Gilbertson*,†
Chemical Biology Program, Department of Pharmacology and Toxicology,
UniVersity of Texas Medical Branch, GalVeston, Texas 77555-0650
Received May 27, 2009
ABSTRACT
An approach that provides symmetrical, unsymmetrical, and asymmetric N-heterocyclic carbene (NHC) ligands is reported. Reaction of iodoethanol
with aniline provides N-(2-iodoethyl)arylamine salts that are then converted to the corresponding iodide. Reaction with aliphatic or aromatic
amines followed by triethyl orthoformate was used to provide 26 different NHC ligands.
The discovery of new catalysts is often limited by the
availability of new ligands. Consequently, the development
of chemistry that provides access to new ligand types is
critical. N-Heterocyclic carbenes (NHCs) have been shown
to provide transition metal complexes that have improved
reactivity and stability over their analogous phosphine
complexes.1-3 An approach for the synthesis of symmetrical,
genation,14,15 hydroformylation,16 alkyne coupling,17 olefin
cyclopropanation,18 arylation of aldehydes,19 and olefin
metathesis20 are all reactions that, in many cases, have been
catalyzed by NHC complexes with greater efficiency than
the usual phosphine complexes.
In addition to being used as ligands on catalytically active
transition metals, the NHC functional group has been very
useful in a wide variety of different reactions catalyzed by
nucleophilic activation.21,22 As organocatalysts, NHC ligands
unsymmetrical, and chiral NHC ligands has been developed.
4
¨
Since their original disclosure by Ofele in 1968 and their
initial isolation by Arduengo,5 NHC ligands have been shown
to be effective as ligands on transition metal complexes that
catalyze a number of reactions. The Heck reaction,6 Suzuki
and Sonogashira couplings,7,8 aryl amination,9,10 amide
R-arylation,11 hydrosilylation,12 Kumada coupling,13 hydro-
(10) Stauffer, S. R.; Lee, S.; Stambuli, J. P.; Hauck, S. I.; Hartwig, J. F.
Org. Lett. 2000, 2, 1423–1426.
(11) Lee, S.; Hartwig, J. F. J. Org. Chem. 2001, 66, 3402–3415.
(12) Enders, D.; Gielen, H. J. Organomet. Chem. 2001, 617-618, 70–
80.
(13) Bohm, V. P.; Weskamp, T.; Gstottmayr, C. W.; Herrmann, W. A.
Angew. Chem., Int. Ed. 2000, 39, 1602–1604.
† Present address: Department of Chemistry, University of Houston,
Houston, TX 77204-5003.
(14) Powell, M. T.; Hou, D.-R.; Perry, M. C.; Cui, X.; Burgess, K. J. Am.
Chem. Soc. 2001, 123, 8878–8879.
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1491–1524
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J. H.; Burgess, K. J. Am. Chem. Soc. 2003, 125, 113–123.
(16) Ko¨cher, C.; Herrmann, W. A. J. Organomet. Chem. 1997, 532,
261–265.
(2) Perry, M. C.; Burgess, K. Tetrahedron: Asymmetry 2003, 14, 951–
961
.
(3) Marion, N.; Nolan, S. P. Acc. Chem. Res. 2008, 41, 1440–1449
.
¨
(4) Ofele, K. J. Organomet. Chem. 1968, 12, P4-P43.
(17) Barratta, W.; Herrmann, W. A.; Rigo, P.; Schwarz, J. J. Organomet.
Chem. 2000, 593, 489–493.
(5) Arduengo, A. J.; Harlow, R. L.; Kline, M. J. Am. Chem. Soc. 1991,
113, 361–363.
¨
(18) Cetinkaya, B.; Ozdemir, I.; Dixneuf, P. H. J. Organomet. Chem.
(6) Yang, C.; Lee, H. M.; Nolan, S. P. Org. Lett. 2001, 3, 1511–1514.
(7) Herrmann, W. A.; Bohm, V. P. W.; Gstottmayr, C. W. K.; Grosche,
M.; Reisinger, C.-P.; Weskamp, T. J. Organomet. Chem. 2001, 617-618,
1997, 534, 153–158.
(19) Furstner, A.; Krause, H. AdV. Synth. Catal. 2001, 343, 343–350.
(20) Sanford, M. S.; Love, J. A.; Grubbs, R. H. J. Am. Chem. Soc. 2001,
123, 6543–6554.
616–628
.
(8) Grasa, G. A.; Viciu, M. S.; Huang, J.; Zhang, C.; Trudell, M. L.;
Nolan, S. P. Organometallics 2002, 21, 2866–2873
(9) Cheng, J.; Trudell, M. L. Org. Lett. 2001, 3, 1371–1374
(21) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290–1309.
.
(22) Nolan, S. P., Ed. N-Heterocyclic Carbenes in Synthesis; Wiley-
VCH Verlag GmbH&Co., 2006
.
.
10.1021/ol901189m CCC: $40.75
Published on Web 07/22/2009
2009 American Chemical Society