times. Inspired by the pioneering work of Brunet,12 a series
of aryl iodides (1a-k) were microwave heated together with
0.66 equiv of Co2(CO)8, the latter acting as a combined Ar-I
activator and carbon monoxide source (Scheme 1). The aryl
Table 1. Ultrafast Generation of Benzophenones under Air in
Sealed Vessels
Scheme 1. Synthesis of Diaryl Ketones Employing Aryl
Iodides
iodides were chosen to cover aspects of sterical hindrance,
different electronic properties, and potentially reactive
functional groups. Initial screening experiments revealed that
inert atmosphere, bases or other additives were unnecessary.
Further, the solvents acetonitrile and propionitrile drastically
expedited the formation of benzophenones (2), while the use
of benzene, THF, DMAc, and DMF afforded only minor
yields of product. Addition of small amounts of water
inhibited the process.
The preparative carbonylation reactions were conducted
on a 0.6 mmol scale under air in sealed microwave
transparent vessels using a commercially available batch
reactor13 for heating. With less than 10 s of directed
irradiation, all starting 1a-j underwent complete conversion
and afforded useful to excellent isolated yields of products
2a-j (57-97%).14 The results are summarized in Table 1.
Notably, the coupling with parent 1e was further optimized
down to 6 s with consistent yield (entry 5). Using the 10 s
standard condition, only electron-rich 1a and sterically
hindered 1b produced unsatisfying yields, mainly due to
competing dehalogenation (entries 1 and 2). The heteroaro-
matic sulfur-containing 1d proved to be a very efficient
coupling partner (entry 4) while coupling with 1k was
unsuccessful. As expected, chemoselective coupling of 1g
was facile due to the reluctance of aryl chlorides to undergo
cobalt-mediated activation.15 Employing 1j furnished a
satisfying preparative outcome, despite the well-known
capacity of nitriles to substitute carbon monoxide and to form
stable complexes with the metal center (entry 10).16,17 In
general, entries 1-7 provided small quantities of benzil side
products while the electron-poor 1h, 1i, and 1j furnished trace
amounts of homocoupled biaryls. No conversion occurs in
the absence of heating regardless of reaction time.
a Isolated yield based on 1 (>95% purity of 2 by GC-MS). b 6 s of
microwave irradiation. c Performed with a preheated oil bath (oil temperature
140 °C) for 2 min using an open reaction vessel. d Not isolated, less than
5% according to GC-MS.
The carbonylative coupling of the more sluggish aryl
bromides was also examined with Co2(CO)8. Despite em-
ploying different irradiation times, temperatures, and amounts
of Co2(CO)8, a smooth and general protocol to exploit aryl
bromides was not identified. At present, incomplete conver-
sions and varying reaction times plague the methodology.
For example, ketones 2e and 2i were both synthesized in
moderate yields (64% and 43%), but very different heating
times were required in the two cases (Scheme 2).
In an attempt to explore the possibility to perform cobalt-
catalyzed carbonylative couplings, nonstoichiometric amounts
of Co2(CO)8 were investigated in the reaction with 1f. Two
conclusions were made from these experiments. First, the
reaction is catalytic with more than one turnover in cobalt
(12) Brunet, J. J.; Taillefer, M. J. Organomet. Chem. 1990, 384, 193-
197.
(13) Stadler, A.; Kappe, C. O. J. Comb. Chem. 2001, 3, 624-630.
(14) The aryl iodide (0.60 mmol), Co2(CO)8 (0.40 mmol, 137 mg), and
2,3-dimethylnaphthalene (0.15 mmol, 23 mg) as internal standard and 2.5
mL of dry acetonitrile were mixed in a septum-capped tube (a Smith process
vial). The microwave synthesizer was set to 250 °C and the heating time to
10 s. After 10 s, the temperature was ca. 130 °C. After cooling, the reaction
mixture was filtered through Celite, concentrated, and purified with silica
chromatography.
(15) Brunet, J. J.; Demontauzon, D.; Taillefer, M. Organometallics 1991,
10, 341-346.
(16) Pa´lyi, G.; Ungvary, F.; Galamb, V.; Marko, L. Coord. Chem. ReV.
1984, 53, 37-53.
(17) Tate, D. P.; Augl, J. M.; Buss, A. Inorg. Chem. 1963, 2, 427-428.
4876
Org. Lett., Vol. 5, No. 25, 2003