Fig. 3. Experimental ob-
servations that are consist-
ent with a radical pathway.
(A) X-band EPR spectrum
of a frozen (77 K) reac-
tion mixture. Parameters
are g = [2.440, 2.055,
1.990]. (B) Cyclization,
followed by C–N bond for-
mation, in a photoinduced
Ullmann reaction of an aryl
iodide bearing a pendant
olefin. (C) Stereochem-
ical study of a photoin-
duced Ullmann reaction.
study in a photoinduced
that deuterium-labeled aryl iodide 4-d furnishes
a 1:1 mixture of diastereomers (Fig. 3C) is fully
consistent with a radical pathway, whereas the
sequence should only produce diastereomer 6-d.
A control experiment established that olefin 4-d
does not undergo cis/trans isomerization under the
reaction conditions. We have also performed this
stereochemical study with the bromo analog of 4-d;
again, a 1:1 mixture of diastereomers is generated,
and no uncyclized products are observed.
An additional mechanistic probe that has
been used to distinguish between concerted
oxidative addition of Ar–X and a pathway involving SET to the haloarene is the relative
reactivity of 1-bromonaphthalene (7) and 4-
chlorobenzonitrile (8) (Fig. 3D) (13). According
to this analysis, if C–X cleavage proceeds via
concerted oxidative addition, then preferential
coupling of 1-bromonaphthalene is expected,
whereas if the reaction occurs via an SET mechanism, then 4-chlorobenzonitrile should react more
rapidly because of its more favorable reduction
potential (–2.03 V for 8; –2.17 V for 7 versus SCE
in DMF) (28).
When copper–carbazolide complex 1 is irradiated in the presence of a 1:1 mixture of
1-bromonaphthalene and 4-chlorobenzonitrile,
Ullmann coupling product 10, derived from
4-chlorobenzonitrile, is predominant (Fig. 3D).
This observation is consistent with a radical-based
SET pathway for C–N bond formation and stands
in sharp contrast with a previous investigation in
which only the bromoarene was reactive, which was
interpreted as supporting a concerted mechanism
for oxidative addition under those conditions (13).
Because copper-catalyzed Ullmann C–N cou-
plings are of substantial interest (6–9), we have
pursued preliminary studies to ascertain whether
turnover can be achieved in these photoinduced
processes. We have determined that irradiation of
iodobenzene and lithium carbazolide in an aceto-
nitrile solution of 10 mole percent (mol %) of
copper–carbazolide complex 1 does indeed fur-
nish the C–N coupling product in 64% yield,
establishing the viability of copper catalysis in
this photochemical reaction manifold (Table 1B,
entry 1). In the absence of light, no detectable
coupling is observed (Table 1B, entry 2), and ir-
radiation of the coupling partners in the absence
of complex 1 leads to very little N-phenylcarbazole
(3%) (Table 1B, entry 3). These copper-catalyzed,
photoinduced Ullmann couplings can even be ef-
fected at –40°C (Table 1B, entry 4). In the pres-
ence of 1.5 mol of copper–carbazolide complex
1, a turnover number of ~20 can be achieved
(Table 1B, entry 5). CuI also serves as a catalyst
for photoinduced Ullmann C–N couplings, likely
via electron transfer from a luminescent copper–
carbazolide complex generated in situ (Table 1B,
entries 6 and 7).
References and Notes
1. A. S. Travis, in Chemistry of Anilines, Z. Rapaport,
Ed. (John Wiley & Sons, New York, 2007), vol. 1,
2. A. S. Travis, in Chemistry of Anilines, Z. Rapaport, Ed.
(John Wiley & Sons, New York, 2007), vol. 2, pp. 715–782.
3. Atorvastatin in the Management of Cardiovascular Risk:
From Pharmacology to Clinical Evidence, S. Grundy, Ed.
(Kluwer, Auckland, New Zealand, 2007).
4. F. Ullmann, Ber. Deutsch. Chem. Ges. 36, 2382
5. I. Goldberg, Ber. Deutsch. Chem. Ges. 39, 1691 (1906).
6. F. Monnier, M. Taillefer, Angew. Chem. Int. Ed. 48,
7. G. Evano, N. Blanchard, M. Toumi, Chem. Rev. 108,
8. I. P. Beletskaya, A. V. Cheprakov, Coord. Chem. Rev. 248,
9. S. V. Ley, A. W. Thomas, Angew. Chem. Int. Ed. 42, 5400
10. L. Jiang, S. L. Buchwald, in Metal-Catalyzed Cross-Coupling
Reactions, A. De Meijere, F. Diederich, Eds. (Wiley–VCH,
New York, 2004), vol. 2, pp. 699–760.
11. J. F. Hartwig, S. Shekhar, Q. Shen, F. Barrios-Landeros, in
Chemistry of Anilines, Z. Rapaport, Ed. (John Wiley &
Sons, New York, 2007), vol. 1, pp. 455–536.