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HBF4P(tBu)3 (4.35 mg, 0.02 mmol) dry THF (4 mL), n-hexylamine
(0.13 mL, 1.00 mmol) and DBU (0.15 mL, 1.00 mmol) in that order.
The chamber was sealed with a screwcap fitted with a Teflon seal.
Chamber B: To chamber B was added SilaCOgen (363.52 mg,
1.50 mmol), dry THF (3 mL) and KF (approx. 60 mg, 1.00 mmol) in
that order. The chamber was sealed with a screwcap fitted with a
Teflon seal and the loaded two-chamber system was removed from
the glovebox and stirred at room temperature for 16 h. The pH of
topically labeled ML137 (37*) in a total yield of 22 % over three
steps from commercially available 2-iodoaniline (Scheme 8).
Conclusions
In conclusion, a new procedure for the facile formation of both
free and N-substituted isatins has been presented starting from
2-iodoanilines. Using a sequential Pd-catalyzed double carbon-
ylation with subsequent acid-mediated cyclization, it was possi-
ble to obtain isatins in good to excellent yields. The carbonyl-
ation reaction makes possible the installation of two 13C-carbon
isotopes. These products can, in turn, be transformed into a
triply labeled indole through reduction by THF:BD3. This ap-
proach was applied to generate selected examples of bioactive
isatins.
the reaction was adjusted to pH = 3 using 2
M HCl (aq) and H2O
(10 mL) was added. The reaction was extracted with CH2Cl2 (3 ×
10 mL), and concentrated in vacuo. The crude material was trans-
ferred to an 8 mL vial using THF (4 mL) and 5
M HCl (aq) (1 mL,
5 mmol) was added. The reaction was stirred for 5 h after which
H2O (10 mL) was added. The reaction was extracted with EtOAc
(3 × 10 mL), washed with brine (10 mL) and dried with MgSO4.
Solvents were removed in vacuo and flash column chromatography
yielded the desired product.
Acknowledgments
The authors are deeply appreciative of generous financial sup-
port of this work from the Danish National Research Foundation
Experimental Section
α-Keto Amides
Chamber A: In an glovebox with argon atmosphere, to chamber A, (grant number DNRF118), the Villum Foundation, the Danish
was added aryl iodide (0.50 mmol), Pd(dba)2 (4.44 mg, 0.01 mmol),
HBF4P(tBu)3 (4.35 mg, 0.02 mmol) dry THF (4 mL), n-hexylamine
(0.13 mL, 1.00 mmol), and DBU (0.15 mL, 1.00 mmol) in that order.
The chamber was sealed with a screwcap fitted with a Teflon seal.
Chamber B: To chamber B was added SilaCOgen (363.52 mg,
1.50 mmol), dry THF (3 mL), and KF (approx. 60 mg, 1.00 mmol) in
that order. The chamber was sealed with a screwcap fitted with a
Teflon seal and the loaded two-chamber system was removed from
the glovebox and stirred at room temperature for 16 h. The pH of
Council for Independent Research: Technology and Production
Sciences, H. Lundbeck A/S and Aarhus University, Denmark.
Keywords: Homogeneous catalysis · Palladium · Nitrogen
heterocycles · Carbon monoxide · Carbonylation ·
Regioselectivity · Isotopic labeling
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Chamber A: In an glovebox with argon atmosphere, to chamber A,
was added aryl iodide (0.50 mmol), Pd(dba)2 (4.44 mg, 0.01 mmol),
HBF4P(tBu)3 (4.35 mg, 0.02 mmol) dry THF (4 mL), n-hexylamine
(0.13 mL, 1.00 mmol), and DBU (0.15 mL, 1.00 mmol) in that order.
The chamber was sealed with a screwcap fitted with a Teflon seal.
Chamber B: To chamber B was added SilaCOgen (363.52 mg,
1.50 mmol), dry THF (3 mL), and KF (approx. 60 mg, 1.00 mmol) in
that order. The chamber was sealed with a screwcap fitted with a
Teflon seal and the loaded two-chamber system was removed from
the glovebox and stirred at room temperature for 16 h. 5
M HCl
(1 mL, 5 mmol) was added and the reaction was stirred for 5 h H2O
(10 mL) was added and the reaction was extracted with EtOAc (3 ×
10 mL), washed with brine (10 mL) and dried with MgSO4. Solvents
were removed in vacuo and flash column chromatography yielded
the desired product.
Isatins (Sequential Procedure)
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was added aryl iodide (0.50 mmol), Pd(dba)2 (4.44 mg, 0.01 mmol),
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Eur. J. Org. Chem. 2016, 1881–1885
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