A R T I C L E S
Zanardi et al.
(727.9): C, 28.05; H, 3.74; N, 7.70. Found: C, 28.24; H, 3.78; N,
7.95. Electrospray MS. Cone 20 V. (m/z, fragment): (692.8,
[M-Cl]+). ESI-TOF-MS (positive mode): monoisotopic peak
692.9963; calc. 692.9935. εr ) 4.0 ppm.
would imply the use of two different catalysts and complicated
workups requiring the isolation of all reaction intermediates.
Connected to this point, the fact that the use of a single well-
defined catalyst (either 2, 3, or 4) yields a better catalytic
outcome than a mixture of two homodimetallic compounds (5
+ 6) results in a clear benefit provided by the heterometallic
species, not only because it affords a more atom-efficient
process, but because it also suggests that the heterometallic
species can improve its catalytic outcome due to catalytic
cooperativity or, at least, it avoids any interference between the
two active metal fragments (an alternative possible explanation
to the poorer outcome shown by the mixture of catalysts).
All three tandem reactions reported here constitute efficient
methods for the generation of complex organic molecules by
one-pot procedures, combining two different processes typically
catalyzed by distinct metal complexes. Among the examples
reported here, the one-pot preparation of biphenyl-substituted
ketones, provides a much easier route to species with potential
pharmaceutical applications.25 The three model reactions are
obviously just the tip of the iceberg if we consider the number
of possible combinations of catalytic transformations that we
can carry out starting from these simple and easy-to-make Ir-Pd
species. This number is even larger if we consider the variety
of heterodimetallic complexes that can be obtained from
triazolylidene ligands.
Synthesis of 3. A mixture of compound 1 (100 mg, 0.17 mmol),
PdCl2 (36 mg, 0.2 mmol), and K2CO3 (70 mg, 0.5 mmol) was heated
overnight in pyridine (3 mL) at 80 °C. The reaction mixture was
filtered through Celite, and the solvent was removed under vacuum.
Pure compound 3 was obtained as a light yellow solid after
precipitation in dichloromethane/n-hexanes. Yield: 102 mg (78%).
3
1H NMR (500 MHz, CDCl3): δ 9.0 (d, JH-H ) 5.5 Hz, 2H, Py),
7.87 (t, 3JH-H ) 7.0 Hz, 1H, Py), 7.45 (t, 3JH-H ) 6.5 Hz, 2H, Py),
4.60 (s, 3H, NCH3), 4.58 (s, 3H, NCH3), 4.41 (s, 3H, NCH3), 1.73
(s, 15H, C5(CH3)5). 13C NMR (125 MHz, CDCl3): δ 168.4 (Ccarbene
- Ir), 163.4 (Ccarbene - Pd), 151.3, 151.1, 138, 124.9, 124.6 (Py),
90.6 (C5(CH3)5), 40.7 (NCH3), 38.1 (NCH3), 37.5 (NCH3), 9.0
(C5(CH3)5). Anal. Calcd. For C20H29Cl4N4IrPd (765.9): C, 31.36;
H, 3.82; N, 7.31. Found: C, 31.77; H, 3.88; N, 7.35. Electrospray
MS. Cone 5 V. (m/z, fragment): (730.8, [M-Cl]+). ESI-TOF-MS
(positive mode): monoisotopic peak 731.0101; calc. 731.0106. εr
) 0.7 ppm.
Synthesis of 4. A mixture of compound 1 (160 mg, 0.27 mmol),
Pd(OAc)2 (28 mg, 0.11 mmol), sodium acetate (12 mg, 0.14 mmol),
and sodium chloride (78 mg, 1.35 mmol) was refluxed overnight
in CH3CN. The reaction mixture was filtered through Celite, and
the solvent was removed under vacuum. The crude was dissolved
in CH2Cl2 and purified by column chromatography. The pure
compound 4 was eluted with acetone/dichloromethane (7:3). Yield
40 mg (13%). 1H NMR (500 MHz, CDCl3): δ 4.46 (s, 12H, NCH3),
4.31 (s, 6H, NCH3), 1.65 (s, 30H, C5(CH3)5). Anal. Calcd. For
C30H48Cl6N6Ir2Pd (1196.3): C, 30.12; H, 4.04; N, 7.02. Found: C,
30.35; H, 4.19; N, 7.08. Electrospray MS. Cone 5 V. (m/z,
fragment): (1161.1, [M-Cl]+) and (562.1, [M-2Cl]2+). ESI-TOF-
MS (positive mode): monoisotopic peak 563.0481; calc. 563.0477.
εr ) 0.7 ppm.
Catalytic Studies. Dehalogenation/Transfer Hydrogenation
of Halo-Acetophenones. In a typical run a capped vessel containing
a stirrer bar was charged with the corresponding 4-haloacetophenone
(0.36 mmol), Cs2CO3 (0.43 mmol), anisole as internal reference
(0.36 mmol), catalyst (2 mol %), and 2 mL of 2-propanol. The
reaction mixture was stirred at 100 °C for the appropriate time.
Reaction monitoring, yields, and conversions were determined by
GC chromatography. Products and intermediates were characterized
by GC/MS. Isolated products were characterized by 1H NMR and
13C NMR after column chromatography purification using n-
hexanes/ethylacetate (9:1).
Experimental Section
General Procedures. Compounds 1,6 5,6 and 612 were prepared
according to literature procedures. All other reagents and solvents
were used as received from commercial suppliers. Synthesis and
catalytic experiments were carried out under aerobic conditions and
without solvent pretreatment. NMR spectra were recorded on Varian
spectrometers operating at 300 or 500 MHz (1H NMR) and 75 and
125 MHz (13C NMR), respectively, and referenced to SiMe4 (δ in
ppm and J in Hertz). NMR spectra were recorded at room
temperature with CDCl3 unless otherwise stated. A QTOF I
(quadrupole-hexapole-TOF) mass spectrometer with an orthogonal
Z-spray-electrospray interface (Micromass, Manchester, UK) was
used. The drying gas as well as nebulizing gas was nitrogen at a
flow of 400 L/h and 80 L/h respectively. The temperature of the
source block was set to 120 °C and the desolvation temperature to
150 °C. A capillary voltage of 3.5 KV was used in the positive
scan mode, and the cone voltage was set to 30 V. Mass calibration
was performed using a solution of sodium iodide in isopropanol:
water (50:50) from m/z 150 to 1000 amu. Sample solutions (aprox
1 × 10-4 M) in dichlormethane:methanol (50:50) were infused via
a syringe pump directly connected to the interface at a flow of 10
µL/min. A 1 µg/mL solution of 3,5-diiodo-L-tyrosine was used as
a lock mass. Elemental analyses were carried out on a EuroEA3000
Eurovector Analyzer. A gas chromatograph GC-2010 (Shimadzu)
equipped with a FID and a Teknokroma (TRB-5MS, 30m × 0.25
mm × 0.25 µm) column and Gas chromatograph/Mass spectrometer
GCMS-QP2010 (Shimadzu) equipped with a Teknokroma (TRB-
5MS, 30m × 0.25 mm × 0.25 µm) column were used.
Suzuki-Miyaura Coupling/Transfer Hydrogenation or
r-Alkylation of Ketones. A capped vessel containing a stirrer bar
was charged with 4-bromoacetophenone (0.36 mmol), phenylbo-
ronic acid (0.55 mmol), Cs2CO3 (1.08 mmol), anisole as internal
reference (0.36 mmol), catalyst 3 (2 mol %), 2 mL of alcohol, and
2 mL of THF. The solution was heated to 100 °C for the appropriate
time. The resulting products were characterized by comparing the
spectroscopic data of the isolated compounds with those reported
in the literature.26
NMR Characterization of F (R ) nBu). 1H NMR (300 MHz,
3
CDCl3): δ 8.03 (d, JH-H ) 8.7 Hz, 2H, Ph), 7.70 - 7.62 (m, 4H,
Synthesis of 2. A mixture of compound 1 (68 mg, 0.11 mmol),
Pd(OAc)2 (30 mg, 0.12 mmol), and sodium chloride (30 mg, 0.52
mmol) was refluxed overnight in CH3CN. The reaction mixture
was filtered through Celite, and the volatiles were removed under
vacuum. The crude was dissolved in CH2Cl2 and purified by column
chromatography. The pure compound 2 was eluted with dichlo-
romethane/methanol (10:1) and precipitated from a mixture of
acetone/diethylether to give a pale yellow solid. Yield 60 mg (68%).
1H NMR (300 MHz, CD3CN): δ 4.45 (s, 3H, NCH3), 4.37 (s, 3H,
NCH3), 4.27 (s, 3H, NCH3), 1.58 (s, 15H, C5(CH3)5), (CH3CN)
3
Ph), 7.48 - 7.40 (m, 3H, Ph), 2.99 (t, JH-H ) 8.9 Hz, 2H, CH2),
1.80 - 1.76 (m, 2H, CH2), 1.42 - 1.38 (m, 4H, CH2), 0.94 (t, 3JH-H
) 6.9 Hz, 3H, CH3). 13C NMR (75 MHz, CDCl3): δ 200.4 (CO),
145.8, 140.2, 136.1 (Cq), 129.2, 128.9, 128.4, 127.5, 127.4 (CH),
38.9, 31.2, 24.4, 22.8 (CH2), 14.2 (CH3).
NMR characterization of F (R ) CH2Ph). 1H NMR (300 MHz,
3
3
CDCl3): δ 8.05 (d, JH-H ) 8.1 Hz, 2H, Ph), 7.68 (d, JH-H ) 8.4
Hz, 2H, Ph), 7.63 (d, 3JH-H ) 7.4 Hz, 2H, Ph), 7.49 - 7.44 (m, 4H,
not observed. 13C NMR (125 MHz, CD3CN): δ 169.0 (Ccarbene
-
(26) Mohrbacher, R. J.; Cromwell, N. H. J. Am. Chem. Soc. 1957, 79, 401.
Henze, H. R.; Long, L. M. J. Am. Chem. Soc. 1941, 63, 1941. Long,
L. M.; Henze, H. R. J. Am. Chem. Soc. 1941, 63, 1939.
Ir), 158.7 (Ccarbene - Pd), 91.1 (C5(CH3)5), 41.1 (NCH3), 38.3 (NCH3),
38.1 (NCH3), 8.8 (C5(CH3)5). Anal. Calcd. For C17H27Cl4N4IrPd
9
14536 J. AM. CHEM. SOC. VOL. 131, NO. 40, 2009