Abstract
A mild, ligand-free method of arylating 2,4-quinazolinediones
using arylboronates in the presence of copper salts is described.
The reaction is tolerant of a variety of functional groups and works
for arylboronic acid, arylboronic ester, and aryltrifluoroboronate
donors. A catalytic variant is also described.
Key words
heterocycle - arylation - copper - cross-coupling - boronic
References and Notes
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19 A regiochemically controlled synthesis
of quinazolinedione 3 was carried out using
the route outlined in Scheme
[¹ 1 , confirming
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nitrogen position and not either of the available carbonyl oxygens.
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Typical Procedure
H ,3H )-dione
(200 mg, 1.14 mmol), 4-methoxyphenylboronic acid (345 mg, 2.27 mmol), Cu(OAc)2 (412
mg, 2.27 mmol), and Et3 N (0.316 mL, 2.27 mmol) were suspended
in CH2 Cl2 (12 mL) along with 200 mg of activated
4 Å MS. The suspension was allowed to stir at r.t. for
20 h then partitioned between 1 M HCl (50 mL) and EtOAc (50 mL).
The organic layer was isolated, dried (MgSO4 ), and concentrated
in vacuo, and the residue was purified by flash chromatography (15% EtOAc-i -hexane) H ,3H )-dione
(4 ) as a colourless solid (230 mg, 72%). ¹ H NMR
(400 MHz, CDCl3 ): δ = 8.1-8.4
(m, 1 H), 7.4-7.6 (m, 1 H), 7.1-7.3 (m, 3 H),
7.0-7.2 (d, 2 H), 6.59 (d, 1 H), 3.89 (s, 3 H), 3.52 (s,
3 H). ¹³ C NMR (100 MHz, CDCl3 ): δ = 162.2,
159.9, 151.2, 141.7, 134.5, 129.9, 129.0, 128.5, 123.0, 115.5, 115.3,
115.0, 55.5, 28.3; MS (ES+ ): m/z = 281 [M - H]+ .
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