A variety of vinyl and aryl azides were examined to
determine if [(cod)Ir(OMe)]2 could catalyze the amination
of aryl or vinyl C-H bonds (Scheme 1). While all azi-
If this mechanism was occurring, the rate of benzylic C-H
bond activation should be retarded when the electron-
withdrawing R2 substituents are present.15 Analogously, the
rate of nucleophilic addition of azide should be attenuated
with electron-deficient R1 substituents. In contrast to these
expectations, aryl azides 8b and 8i exhibited nearly equal
reactivity toward [(cod)Ir(OMe)]2 and the more electron-
deficient 8g reacted faster than 8b. These results suggest that
a benzylic C-H bond activation/nucleophilic addition mech-
anism does not account for N-heterocycle formation.
Scheme 1. Comparison of Catalytic Efficiency of Ir(I) versus
Rh(II) for Aromatic N-Heterocycle Formation
The faster rate of indoline formation by the electron-
deficient aryl azide 8g as well as the production of aniline,
a common nitrene decomposition product, suggests that an
electrophilic iridium nitrenoid (14) is generated in the
mechanism (Scheme 3).3,16 This species could be produced
Scheme 3. Potential Mechanism for Benzylic C-H Amination
doacrylates tested (cf. 10a) were found to be unreactive
toward [(cod)Ir(OMe)]2, aryl azides were cleanly converted
to indoles or carbazoles (11b-11i) by [(cod)Ir(OMe)]2 in
comparable yields to Rh2(O2CC3F7)4. Enhanced regioselec-
tivity was observed in the reaction of 10i with [(cod)-
Ir(OMe)]2 as compared to Rh2(O2CC3F7)4. These substrates,
however, required higher reaction temperatures (40 °C) and
increased catalyst loading (5 mol %) of iridium than aryl
azides 8. The reactivity of aryl azides 10 was also not
dependent on the electronic nature of their substituents. These
differences suggest that a different mechanism (or rate-
determining step) might be operating for aromatic N-
heterocycle formation than for indoline formation.
by coordination of the aryl azide with the iridium catalyst
(to form R-13 or γ-13)17 followed by extrusion of N2.
Carbon-nitrogen bond formation could then occur by two
different pathways: a concerted insertion of the nitrenoid via
15 or hydrogen-atom abstraction (to form 16) followed by
radical recombination.18,19
Several intermolecular competition experiments were
performed to determine if C-H bond activation accounted
for indoline formation (Scheme 2).13 In this mechanism,
(11) The pyrolysis of ortho-alkyl substituted aryl azides produces
indolines in moderate to good yields: for example, 3-methylindoline (44%),
2-ethylindoline (55%), hexahydrocarbazole (86%). See: ref 9b and Smo-
linsky, G. J. Org. Chem. 1961, 26, 4108
.
Scheme 2. Intermolecular Competition Experiments
(12) Irradiation of ortho-alkyl-substituted aryl azides leads to varied
yields of indolines: while insertion of the nitrene into a tertiary C-H bond
occurs to form 50% of the indoline (see ref 9d), insertion into a secondary
C-H bond produces only 11% of the indoline product (see ref 9d)
.
(13) For recent, leading mechanistic studies of related iridium-mediated
C–H bond activations, see: (a) ref 1a and 1b. (b) Yung, C. M.; Skaddan,
M. B.; Bergman, R. G. J. Am. Chem. Soc. 2004, 126, 13033. (c) Boller,
T. M.; Murphy, J. M.; Hapke, M.; Ishiyama, T.; Miyaura, N.; Hartwig,
J. F. J. Am. Chem. Soc. 2005, 127, 14263. (d) Tenn, W. J.; Young, K. J. H.;
Oxgaard, J.; Nielsen, R. J.; Goddard, W. A.; Periana, R. A. Organometallics
2006, 25, 5173. (e) Zhu, Y.; Fan, L.; Chen, C.-H.; Finnell, S. R.; Foxman,
B. M.; Ozerov, O. V. Organometallics 2007, 26, 6701
(14) For iridium η3-benzyl complexes, see: Fryzuk, M. D.; McConville,
D. H.; Rettig, S. J. J. Organomet. Chem. 1993, 445, 245
.
.
(15) For a discussion of the effect of aryl-substitution on benzylic C-H
bond activation, see: (a) Driver, T. G.; Day, M. W.; Labinger, J. A.; Bercaw,
J. E. Organometallics 2005, 24, 3644. (b) Heyduk, A. F.; Driver, T. G.;
Labinger, J. A.; Bercaw, J. E. J. Am. Chem. Soc. 2004, 126, 15034
.
(16) For recent reports of Ir-catalyzed C-atom-transfer reactions, see:
(a) Lebel, H.; Ladjel, C. Organometallics 2008, 27, 2676. (b) Whited, M. T.;
Grubbs, R. H. J. Am. Chem. Soc. 2008, 130, 5874. (c) Suematsu, H.;
activation of the benzylic C-H bond2 by the iridium catalyst
produces η3-benzyl 12.14 Subsequent nucleophilic attack by
the pendant azide then forms the C-N bond in the indoline.
Kanchiku, S.; Uchida, T.; Katsuki, T. J. Am. Chem. Soc. 2008, 130, 10327
(17) For the crystal structure of benzyl azide coordinated to an Ir(III)-
.
complex through the R-N-atom, see: Albertin, G.; Antoniutti, S.; Baldan,
D.; Castro, J.; Garcia-Fontan, S. Inorg. Chem. 2008, 47, 742
.
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Org. Lett., Vol. 11, No. 16, 2009