Palladium-Catalyzed Reaction
of Arenediazonium Tetrafluoroborates with Methyl 4-Hydroxy-2-butenoate:
An Approach to 4-Aryl Butenolides and an Expeditious Synthesis of
Rubrolide E
Sandro Cacchi*, Giancarlo Fabrizi, Antonella Goggiamani, Alessio Sferrazza Dipartimento di Chimica e Tecnologie del
Farmaco, Università degli Studi ‘La
Sapienza’, P. le A. Moro 5, 00185 Rome,
Italy Fax: +39(06)49912780; e-Mail: sandro.cacchi@uniroma1.it;
Further Information
Publication History
Received
10 February 2009 Publication Date: 08 April 2009 (online)
The palladium-catalyzed reaction of arenediazonium tetrafluoroborates
with methyl 4-hydroxy-2-butenoate in MeOH under mild conditions
gives 4-arylbutenolides usually in good to high yields through a
domino vinylic substitution/cyclization process. The reaction
tolerates a variety of useful substituents including the whole range
of halogen substituents, nitro, ether, cyano, keto, and ester groups
and can be performed as a one-pot process generating the arenediazonium
salt in situ. By using this method, the marine antibiotic rubrolide
E has been synthesized via an expeditious and efficient sequential
protocol that omits the isolation of the butenolide intermediate
(two operative steps, 52% overall yield).
1 For an excellent recent review on
the palladium chemistry of arenediazonium salts, see: Roglans A.
Pla-Quintana A.
Moreno-Mañas M.
Chem. Rev.
2006,
106:
4622
2mNelson ML.
Ismail MY.
McIntyre L.
Bhatia B.
Viski P.
Hawkins P.
Rennie G.
Andorsky D.
Messersmith D.
Stapleton K.
Dumornay J.
Sheahan P.
Verma AK.
Warchol T.
Levy SB.
J.
Org. Chem.
2003,
68:
5838
Typical Procedure
for the Preparation of Butenolides (3)
To a stirred
solution of 2b (58.0 mg, 0.50 mmol) and Pd(OAc)2 (5.6
mg, 0.025 mmol) in anhyd MeOH (5.0 mL), 1b (250.0
mg, 1.0 mmol) was added at r.t. under argon. The reaction mixture
was warmed at 40 ˚C and stirred at that temperature
for 4 h (the reactor was protected from light with aluminum film).
After cooling, the reaction mixture was diluted with EtOAc, washed
with brine, dried over Na2SO4, and concentrated
under reduced pressure. The residue was purified by chromatography
on SiO2 [n-hexane-EtOAc,
60:40] to afford 83.9 mg of 3b (77% yield);
mp: 192-194 ˚C. IR (KBr): 1745, 1710,
1280 cm-¹. ¹H NMR (400
MHz, CDCl3): δ = 8.15 (d, J = 8.4 Hz,
2 H), 7.60 (d, J = 8.4
Hz, 2 H), 6.21 (t, J = 1.6
Hz, 2 H), 5.16 (d, J = 1.6 Hz,
2 H), 3.97 (s, 3 H). ¹³C NMR (100.6
MHz, CDCl3): δ = 173.2, 166.0, 162.5,
133.6, 132.9, 130.5, 126.5, 115.3, 70.9, 52.6. MS: m/z (%) = 216
(8) [M+], 75 (42), 59 (100).
One-Pot Procedure
for the Preparation of Butenolides (3) from Anilines A
solution of BF3˙OEt2 (140 µL,
1.1 mmol) in anhyd THF (1 mL) was cooled at -15 ˚C,
and 4-carbomethoxylaniline (151.2 mg, 1 mmol) was added.Then, tert-butyl
nitrite (160 µL, 1.3 mmol) in 1 mL of the same solvent
was added dropwise to the rapidly stirred solution over a 10 min
period. After that, the reaction temperature was maintained at -15 ˚C for
10 min, allowed to warm to 5 ˚C (ice-water bath)
over a 20 min period, warmed to r.t., and stirred at the same temperature
till the disappearance of the starting aniline. The reaction mixture
was subsequently concentrated under reduced pressure and diluted
with anhyd MeOH (5 mL). Then, 2b (58.0
mg, 0.50 mmol) and Pd(OAc)2 (5.6 mg, 0.025 mmol) were
added, the reaction mixture was warmed at 40 ˚C,
and stirred at that temperature for 4 h (the reactor was protected
from light with aluminum film). After cooling, the reaction mixture
was diluted with EtOAc, washed with brine, dried over Na2SO4,
and concentrated under reduced pressure. The residue was purified
by chromatography on SiO2 [n-hexane-EtOAc,
60:40] to afford 80.0 mg of 3b (73% yield).