Communication
Experimental Section
Representative procedure for the synthesis of
isoquinolinones
A vial (12 or 6 mL) was charged with Pd(OAc)2 (5 mol%), BuPAd2
(10 mol%), and a stirring bar. Then, 1-bromo-2-fluorobenzene
(0.5 mmol), DBU (4.0 equiv), and DMAc (3 mL) were injected under
argon by using a syringe. The vial (or several vials) was placed in
an alloy plate, which was transferred into a 300 mL autoclave of
the 4560 series from Parr Instruments under argon atmosphere.
After flushing the autoclave three times with CO, a pressure of
15 bar of CO was adjusted at ambient temperature. Then, the reac-
tion was performed for 21 h at 1208C. After the reaction was com-
plete, the autoclave was cooled down with ice water to room tem-
perature and the pressure was released carefully. The solution was
extracted with ethyl acetate (EA) or CH2Cl2, then with saturated
brine (3ꢁ5 times) and dried with MgSO4. After evaporation of the
organic solvent, the residue was adsorbed on silica gel and the
crude product was purified by column chromatography using EA/
pentane as eluent.
Scheme 4. Proposed reaction mechanism for the synthesis of
quinazolinones.
rangement of the C=N bond was indirectly proven by the for-
mation of 1,2-diphenylquinazolin-4(1H)-one ac (Scheme 4).
In addition to amidines, 2-aminoimidazoles and 2-thiolben-
zoimidazole were tested as coupling partners under our opti-
mized conditions. As expected, 5H-benzo[d]benzo[4,5]imidazo-
[2,1-b][1,3]thiazin-5-one was isolated in a high yield (85%) in
the presence of Pd(OAc)2/BuPAd2 (Table 4, ad). Under the same
conditions, benzo[4,5]imidazo[1,2-a]quinazolin-5(6H)-one was
produced in 62% yield from 1H-benzo[d]imidazol-2-amine and
1-bromo-2-fluorobenzene (Table 4, ae).
Representative procedure for the synthesis of
isochromenones
A vial (12 or 6 mL) was charged with (Pd(cinnamyl)Cl)2 (3 mol%),
DPPB (9 mol%), 2-phenylacetophenone, Cs2CO3, and a stirring bar.
Then, 1-bromo-2-fluorobenzene (0.5 mmol) and DMAc (3 mL) were
injected under argon by using a syringe. The vial (or several vials)
was placed in an alloy plate, which was transferred into a 300 mL
autoclave of the 4560 series from Parr Instruments under argon at-
mosphere. After flushing the autoclave three times with CO, a pres-
sure of 50 bar of CO was adjusted at ambient temperature. Then,
the reaction was performed for 40 h at 1408C. After the reaction
was complete, the autoclave was cooled down with ice water to
room temperature and the pressure was released carefully. The so-
lution was extracted with ethyl acetate or CH2Cl2, then with satu-
rated brine (3ꢁ5 times) and dried with MgSO4. After evaporation
of the organic solvent, the residue was adsorbed on silica gel and
the crude product was purified by column chromatography using
EA/pentane as eluent.
Table 4. Palladium-catalyzed carbonylative synthesis of other hetero-
cycles.[a]
ad, 85%
ae, 62%
af, 16%[b]
[a] Reaction conditions: 1-bromo-2-fluorobenzene (0.5 mmol), 2-amino-
imidazole (1.0 equiv), Pd(OAc)2 (2 mol%), BuPAd2 (6 mol%) NEt3
(3.0 equiv), DMAc (3 mL), CO (5 bar), 1208C, 22 h. Yield of the isolated
product. [b] Pd(OAc)2 (5 mol%), BuPAd2 (10 mol%) NEt3 (3.0 equiv), DMAc
(3 mL), CO (15 bar), 1408C, 41 h.[9]
Representative procedure for the synthesis of
quinazolinones
A vial (12 or 6 mL) was charged with Pd(OAc)2 (2 mol%), BuPAd2
(6 mol%), amidine and a stirring bar. Then, 1-bromo-2-fluoroben-
zene (0.5 mmol), DiPEA (4.0 equiv) and DMAc (3 mL) were injected
under argon by using a syringe. The vial (or several vials) was
placed in an alloy plate, which was transferred into a 300 mL auto-
clave of the 4560 series from Parr Instruments under argon atmos-
phere. After flushing the autoclave three times with CO, a pressure
of 10 bar of CO was adjusted at ambient temperature. Then, the
reaction was performed for 22 h at 1408C. After the reaction was
complete, the autoclave was cooled down with ice water to room
temperature and the pressure was released carefully. The solution
was extracted with ethyl acetate or CH2Cl2, then with saturated
brine (3ꢁ5 times) and dried with MgSO4. After evaporation of the
organic solvent, the residue was adsorbed on silica gel and the
crude product was purified by column chromatography using EA/
pentane as eluent.
In summary, a systematic study on the palladium-catalyzed car-
bonylative transformation of 1-bromo-2-fluorobenzenes with
various nucleophiles has been performed. By the merge of
a carbonylative coupling and nucleophilic substitution, the de-
sired six-membered isoquinolinones, isochromenones, and qui-
nazolinones were formed in low to excellent yields. It is worth
noting that the combination of carbonylative coupling and nu-
cleophilic substitution offers an ideal route for the preparation
of heterocycles that are usually difficult to prepare by other
methodologies.
Chem. Eur. J. 2014, 20, 16107 – 16110
16109
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