(COD)IrPnBu3(IMe) 8a, and (COD)IrPnBu3(IMes) 8b. When
applied within attempted labelling processes with acetophe-
none, complex 8a, bearing the considerably less bulky IMe
ligand, was completely inactive. In contrast, complex 8b is a
competent exchange catalyst over a range of substrates.
Having stated this, complex 8b was not as generally effective
(e.g. only a 56% D incorporation with 2-phenylpyridine at 5
mol% loading) as the iridium species, 5a–c. Further studies
into general ligand effects in this area are ongoing and will be
reported in due course.
Notes and references
z CCDC 634672. For crystallographic data in CIF or other electronic
format, see DOI: 10.1039/b715938b
1 J. L. Garnett and R. J. Hodges, J. Am. Chem. Soc., 1967, 89, 4546.
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Finally, since benzanilides are capable of labelling through
both a 5 and a 6 mmi (see 7i, Table 2), we wondered whether
the new catalyst systems could be employed to deliver selective
exchange within such substrates; this would be of considerable
practical use, particularly for application in pharmaceutically-
based metabolism studies. As shown in Scheme 3, complex 5c
shows very high isotope incorporation via both possible
metallocyclic intermediates at 5 mol% loading. Pleasingly,
reduction in catalyst 5c loading has a dramatic effect upon
the level of D incorporation into the position (b) activated
through a 6 mmi, while the position (a), labelled via a 5 mmi,
sees consistently high D uptake. This study illustrates a further
distinct practical advantage delivered by these novel iridium
catalyst systems. To our knowledge, this level of labelling
selectivity is unprecedented in the literature.
3 (a) R. H. Crabtree, E. M. Holt, M. Lavin and S. M. Morehouse,
Inorg. Chem., 1985, 24, 1986; (b) R. Heys, J. Chem. Soc., Chem.
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1996, 524, 87; (e) J. G. Ellames, S. J. Gibson, J. M. Herbert, W. J.
Kerr and A. H. McNeill, Tetrahedron Lett., 2001, 42, 6413; (f) P.
W. C. Cross, J. G. Ellames, J. S. Gibson, J. M. Herbert, W. J. Kerr,
A. H. McNeill and T. W. Mathers, Tetrahedron, 2003, 59, 3349; (g)
J. G. Ellames, J. S. Gibson, J. M. Herbert, W. J. Kerr and A. H.
McNeill, J. Labelled Compd. Radiopharm., 2004, 47, 1; (h) M. B.
Skaddan, C. M. Yung and R. G. Bergman, Org. Lett., 2004, 6, 11;
(i) C. M. Yung, M. B. Skaddan and R. G. Bergman, J. Am. Chem.
Soc., 2004, 126, 13033; (j) R. N. Garman, M. J. Hickey, L. P.
Kingston, B. McAuley, J. R. Jones, W. J. S. Lockley, A. N. Mather
and D. J. Wilkinson, J. Labelled Compd. Radiopharm., 2005, 48,
75; (k) J. Kruger, B. Manmontri and G. Fels, Eur. J. Org. Chem.,
¨
2005, 1402; (l) M. B. Skaddan and R. G. Bergman, J. Labelled
Compd. Radiopharm., 2006, 49, 623.
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P. R. Das and B. Evans, J. Labelled Compd. Radiopharm., 1995, 36,
497.
5 G. J. Ellames, J. S. Gibson, J. M. Herbert and A. H. McNeill,
Tetrahedron, 2001, 57, 9487.
6 H. M. Lee, T. Jiang, E. D. Stevens and S. P. Nolan, Organome-
tallics, 2001, 20, 1255.
´
7 (a) L. D. Vasquez-Serrano, B. T. Owens and J. M. Buriak, Chem.
Commun., 2002, 2518; (b) L. D. Vazquez-Serrano, B. T. Owens and
J. M. Buriak, Inorg. Chim. Acta, 2006, 359, 2786.
8 (a) A. J. Arduengo, III, R. L. Harlow and M. Kline, J. Am. Chem.
Soc., 1991, 113, 361; (b) A. J. Arduengo, III, Acc. Chem. Res.,
Scheme 3 Selectivity for a 5 mmi over a 6 mmi with catalyst 5c.
1999, 32, 913; (c) W. A. Herrmann and C. Kocher, Angew. Chem.,
¨
Int. Ed. Engl., 1997, 36, 2162; (d) T. Westkamp, V. P. W. Bohm
and W. A. Herrmann, J. Organomet. Chem., 2000, 600, 12; (e) W.
A. Herrmann, Angew. Chem., Int. Ed., 2002, 41, 1290; (f) It should
be noted that Cp*Ir(NHC)(dihalide) complexes have recently been
reported and used in HIE processes under relatively forcing
conditions, with CD3OD (or (CD3)2CO) as the deuterium source;
see: R. Corberan, M. Sanau and E. Peris, J. Am. Chem. Soc., 2006,
128, 3974.
In summary, practically accessible methods for the prepara-
tion of a range of novel, robust, and readily handleable
iridium(I) complexes, bearing a bulky NHC–phosphine ligand
combination, have been established. These complexes have
revealed catalytic activity in exchange processes far in excess of
the industry standard, Crabtree’s catalyst, with excellent levels
of labelling being achievable over short reaction times and at
extremely low metal complex loadings. The ability to perform
selective labelling via a 5 mmi, over a 6 mmi, has also been
shown to be possible. One further practical benefit relates to
the prolonged stability of these complex species; for example,
following storage under an air atmosphere at room tempera-
ture for over 8 months, complex 5c (5 mol% loading) was
shown to be significantly active in delivering 95% D incor-
poration within substrate 6d after 16 h at room temperature.
We thank the University of Strathclyde for a Postgraduate
9 C. Kocher and W. A. Herrmann, J. Organomet. Chem., 1997, 532,
261.
10 Crystal Data for 5cꢁ0.35CCl2H2ꢁ0.3H2O: C37.35H48.3Cl0.7F6Ir-
ꢀ
N2O0.3P2 Triclinic space group P1,
a
=
11.4652(2)
b
=
13.3037(2) c = 14.1374(3) A, a = 86.555(1) b = 67.108(1), g =
71.527(1)1, V = 1879.25(6) A3, T = 123 K, Z = 2, 2ymax = 55.081,
MoKa l = 0.71073 A. The structure was solved and refined on F2
(SHELXS and SHELXL-97; G. M. Sheldrick, University of
Gottingen, Germany) to convergence at R1 = 0.0280 (for 7433
¨
reflections with I 4 2s(I)) wR2 = 0.0528 and S = 1.018 for 469
parameters and 8614 unique reflections. Minimum/maximum re-
sidual electron density ꢂ0.573/0.850 e Aꢂ3. CCDC 634672. For
crystallographic data in CIF or other electronic format, see DOI:
10.1039/b715938b.
Studentship (J.A.B.), AstraZeneca, R&D Molndal for
¨
11 Following the completion of this preparative work, one of these
complexes (5d) was reported in the literature, having been prepared
by an alternative and more synthetically demanding route; see
ref. 7b.
postgraduate studentship funding (S.I.), and the EPSRC
Mass Spectrometry Service, University of Wales, Swansea,
for analyses.
ꢀc
This journal is The Royal Society of Chemistry 2008
Chem. Commun., 2008, 1115–1117 | 1117