pubs.acs.org/joc
Contemporary efforts have been directed toward the devel-
Kinetic and Thermodynamic Evaluation of the
Reversible N-Heterocyclic Carbene-Isothiocyanate
Coupling Reaction: Applications in Latent Catalysis
opment of latent catalysts that generate N-heterocyclic
carbenes (NHCs).2 NHCs are a diverse class of reactive species
that are known to catalyze numerous reactions,3 including
the [2 þ 2 þ 2] cyclotrimerization of isocyanates4 and the
polymerization of lactide and other monomers.5 Previous
reports of using NHC adducts as latent catalysts generally
contain either transition metals or carbon dioxide.6,7 While
these adducts are effective, only the NHC component may be
altered to tune the activation temperature, which can influ-
ence the reactivity of the carbene catalyst generated. To
expand the utilities of latent catalysts involving NHCs and to
access adducts which do not involve transition metals, there is
a need to develop other organic coupling partners that rever-
sibly react with NHCs.
Brent C. Norris, Daniel G. Sheppard, Graeme Henkelman,
and Christopher W. Bielawski*
Department of Chemistry and Biochemistry, The University of
Texas at Austin, 1 University Station, A5300, Austin,
Texas 78712, United States
Received September 19, 2010
Recently, we discovered8 that the reaction9,10 between
NHCs and isothiocyanates is thermally reversible and demon-
strated that appropriately functionalized ditopic derivatives
may be used to prepare structurally dynamic polymers. More-
over, we found that the reversibility of the reaction depended
on the structure and electronic properties of the coupling
partners. Building on these results, we reasoned that NHC-
isothiocyanate adducts may find utility as latent catalysts,
and we describe our efforts toward achieving that goal herein.
Since the thermodynamic parameters of the NHC-
isothiocyanate coupling reaction are essential to predicting the
concentration of the carbene catalyst that may ultimately be
generated upon activation, initial efforts were directed toward
studying a reaction involving two prototypical substrates:
1,3-dimesitylimidazolylidene (1) and phenyl isothiocyanate (2).
Using stopped flow and other spectroscopic techniques,
the thermodynamic parameters of the coupling reaction
between 1,3-dimesitylimidazolylidene and phenyl iso-
thiocyanate were determined (Ho = -96.1 kJ mol-1 and
ΔSo = -39.6 J mol-1 K-1). On the basis of these data
which indicated that the reaction was reversible (Keq
=
5.94 ꢀ 1014 M-1 at 25 °C; kf = 252 M-1 s-1; kr = 4.24 ꢀ
10-13 s-1), the adduct formed from the two aforemen-
tioned coupling partners was used as a latent catalyst to
facilitate the [2 þ 2 þ 2] cyclotrimerization of phenyl
isocyanate and the polymerization of DL-lactide.
(3) For excellent reviews on the utilities of NHCs as organocatalysts, see:
(a) Enders, D.; Niemeier, O.; Henseler, A. Chem. Rev. 2007, 107, 5606–5655.
ꢀ
´
ez-Gonzalez, S.; Nolan, S. P. Angew. Chem., Int. Ed. 2007,
(b) Marion, N.; Dı
46, 2988–3000.
(4) Duong, H. A.; Cross, M. J.; Louie, J. Org. Lett. 2004, 6, 4679–4681.
€
(5) (a) Connor, E. F.; Nyce, G. W.; Myers, M.; Mock, A.; Hedrick, J. L.
J. Am. Chem. Soc. 2002, 124, 914–915. (b) Culkin, D. A.; Jeong, W.; Csihony,
S.; Gomez, E. D.; Hedrick, J. L.; Balsara, N. P.; Waymouth, R. M. Angew.
Chem., Int. Ed. 2007, 46, 2627–2630. (c) Raynaud, J.; Absalon, C.; Gnanou,
Y.; Taton, D. J. Am. Chem. Soc. 2009, 131, 3201–3209. (d) Lohmeijer,
B. G. G.; Dubois, G.; Leibfarth, F.; Pratt, R. C.; Nederberg, F.; Nelson, A.;
Waymouth, R. M.; Wade, C.; Hedrick, J. L. Org. Lett. 2006, 8, 4683–4686.
(6) (a) Van Ausdall, B. R.; Glass, J. L.; Wiggins, K. M.; Aarif, A. M.;
Louie, J. J. Org. Chem. 2009, 74, 7935–7942. (b) Duong, H. A.; Tekavec,
T. N.; Arif, A. M.; Louie, J. Chem. Commun. 2004, 112–113.
Latent catalysts are generally inert under ambient conditions
but become activated upon the application of an external
stimulus, such as heat or light. They have found utility in a
broad range of applications, including adhesives, photo-
resists (i.e., Novolac), and packaging for “flip chip” circuits.1
(7) For examples of using NHC-CO2 adducts as precursors to metal
complexes, see: (a) Voutchkova, A. M.; Appelhans, L. N.; Chianese, A. R.;
Crabtree, R. H. J. Am. Chem. Soc. 2005, 127, 17624–17625. (b) Tudose, A.;
Demonceau, A.; Delaude, L. J. Organomet. Chem. 2006, 691, 5356–5365.
(c) Sauvage, X.; Demonceau, A.; Delaude, L. Adv. Synth. Catal. 2009, 351,
2031–2038. For examples of using NHC-CO2 adducts as latent catalysts for
the synthesis of cyclic carbonates, see: (d) Zhou, H.; Zhang, W.-Z.; Liu,
C.-H.; Qu, J.-P.; Lu, X.-B. J. Org. Chem. 2008, 73, 8039–8044.
(1) (a) Smith, J. D. B. In Epoxy Resin Chemistry; Bauer, R. S., Ed.;
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S. P.; Hill, L. W. J. Coat. Technol. 1981, 53, 43–51. (c) Muizebelt, M. J.
J. Coat. Technol. 1985, 57, 43–44. (d) Endo, T.; Sanda, F. Macromol. Symp.
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€
(2) (a) Nyce, G. W.; Glauser, T.; Connor, E. F.; Mock, A.; Waymouth,
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(9) The products obtained from NHC-isothiocyanate coupling have
been shown to engage in 1,3-dipolar additions with alkynes and arynes,
see: (a) Liu, M.-F.; Wang, B.; Cheng, Y. Chem Commun. 2006, 1215–1217.
(b) Zhu, Q.; Liu, M.-F.; Bo, W.; Cheng, Y. Org. Biomol. Chem. 2007, 5, 1282–
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(10) For early examples of using NHC-isothiocyanate adducts in 1,3-
dipolar cycloaddition reactions, see: (a) Winberg, H. E.; Coffman, D. D.
€
J. Am. Chem. Soc. 1965, 2776–2777. (b) Regitz, M.; Hocker, J.; Schossler,
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DOI: 10.1021/jo101850g
r
Published on Web 12/01/2010
J. Org. Chem. 2011, 76, 301–304 301
2010 American Chemical Society