Palladium-catalyzed coupling reaction of acylzirconocene chlorides
with hypervalent iodonium salts: synthesis of aryl-substituted
ketones
1
Suk-Ku Kang* and Seok-Keun Yoon
Department of Chemistry, Institute for Basic Sciences, Sungkyunkwan University,
Natural Science Campus, Suwon 440-746, Korea
Received (in Cambridge, UK) 30th November 2001, Accepted 11th January 2002
First published as an Advance Article on the web 24th January 2002
The palladium-catalyzed acylation reaction of alkenoyl-
and alkanoylzirconocene chlorides with hypervalent
iodonium salts afforded the acylated aromatic compounds
under mild conditions.
3i12 in 77, 78, and 84% yields, respectively (entries 7–9). This
coupling method was extended to the substituted alkenes.
The hydrozirconation followed by carbonylation of styrene 1d
gave the alkyl-substituted zirconocene chloride, which readily
coupled with 2a to afford ketone 3j13 in 70% yield (entry 10).
Under the same conditions with 2b and 2c, 3k13 and 3l14 were
afforded (entries 11 and 12). Finally, it is notable that the alkyl-
substituted zirconocene from oct-1-ene 1e, Cp2Zr(H)Cl and
CO coupled with 2a, 2b, and 2c to give 3m,15 3n,16 and 3o17 in
moderate yield (entries 13–15).
Alkenyl- and alkyl substituted acylzirconocene dichlorides,
which are stable and readily available complexes through
hydrozirconation of alkynes and alkenes with zirconocene
hydrochloride (Cp2ZrHCl, Schwartz reagent),1 with subsequent
insertion of carbon monoxide2 are versatile intermediates as
“unmasked” acyl anions for the preparation of aldehydes,
carboxylic acids, ketols, and alkylketones as developed by
Hanzawa and Taguchi and their co-workers.3 Alkyl-substituted
acylzirconium chloride as an “unmasked” acyl anion was
coupled with iodobenzene and utilizing the palladium-catalyst
under harsh conditions at 100 ЊC for 20 h gave alkyl phenyl
ketone in a low (32%) yield. It is necessary to conduct this
coupling under milder conditions and to obtain a better
yield. In connection with our program to utilize hypervalent
iodonium salts in cross-coupling reactions,4 we have found
that hypervalent iodonium salts are excellent electrophiles
in the palladium-catalyzed coupling reaction of alkenyl-
and alkyl-substituted acylzirconocene chlorides, to form aryl-
substituted alkyl and vinyl ketones under mild conditions
(Scheme 1).
In summary, the palladium-catalyzed acylation of alkenoyl-
and alkanoylzirconocene and carbonylation was accomplished
with hypervalent iodonium salts to afford acylated aromatic
compounds under mild conditions.
Experimental
Typical procedure for the synthesis of 1,3-diphenylprop-2-enone
3a
To a stirred solution of Cp2Zr(H)Cl (469 mg, 1.82 mmol) in dry
THF (10 mL) at room temperature under a nitrogen balloon
was added phenylacetylene 1a (93 mg, 0.91 mmol) and the
reaction mixture was stirred for 30 min. After the nitrogen
balloon was changed to a CO balloon, the mixture was stirred
for 2 h at room temperature. To this solution was added
diphenyliodonium tetrafluoroborate 2a (335 mg, 0.91 mmol)
and Pd(PPh3)4 (53.2 mg, 0.045 mmol) and the reaction mixture
was stirred for 2 h. The reaction mixture was extracted with
diethyl ether (20 mL × 3) and the organic layer was dried over
MgSO4, and evaporated in vacuo. The crude product was
separated by SiO2 column chromatography (hexanes–EtOAc =
10 : 1, Rf = 0.35) to give 1,3-diphenylprop-2-enone 3a (142 mg,
75%).
Scheme 1
The results of palladium-catalyzed cross-coupling of the
acylzirconocene chlorides with hypervalent iodonium salts are
summarized in Table 1.
Acknowledgements
(E)-β-Styrylacylzirconocene chloride prepared in situ from
phenylacetylene 1a, Cp2Zr(H)Cl, and carbon monoxide was
reacted in the presence of Pd(PPh3)4 (5 mol%) at room tem-
perature for 2 h to afford the α,β-unsaturated aromatic ketone
3a5 in 75% yield (entry 1 in Table 1). Under the same conditions
with (p-methoxyphenyl)(phenyl)iodonium tetrafluoroborate
(2b) as an electrophile, the p-methoxyphenyl substituted α,β-
unsaturated ketone 3b6 was afforded as the sole product in
73% yield (entry 2). This method was applied to the alkenyl-
substituted iodonium salt 2c. β-Styrylacylzirconocene chloride
generated in situ was treated with alkenyl-substituted iodonium
salt 2c to provide dibenzylideneacetone 3c7 in 83% yield (entry
3). Alkyl-substituted acetylene 1b was utilized in the hydro-
zirconation and carbon monoxide insertion followed by the
palladium-catalyzed coupling with 2a, 2b, and 2c to give the
coupled products 3d,8 3e,9 and 3f10 in 94, 70, and 75% yields,
respectively (entries 4–6). Propargyl alcohol methyl ether (1-
methoxyprop-2-yne) 1c was converted to the corresponding
acylzirconocene chloride and then coupled in the presence of
palladium catalyst with 2a, 2b, and 2c to furnish 3g,11 3h,11 and
The authors wish to acknowledge the financial support from
the National Research Lab (NRL) program and the Korea
Research Foundation (KRF0-2000-015-DP0262). KOSEF-
CMDS is gratefully acknowledged. S.-K. Yoon acknowledges
financial support from the BK21 program.
References
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(b) J. Schwartz and J. A. Labinger, Angew. Chem., Int. Ed. Engl.,
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Press, Oxford, 1995, Vol. 12, pp. 39.
2 Reviews: (a) P. Wipf and H. Jahn, Tetrahedron, 1996, 52, 12853;
(b) J. A. Labinger, Comprehensive Organic Synthesis, eds. B. M.
Trost, and I. Fleming, Pergamon Press: Oxford, 1991, Vol. 8,
pp. 667. Insertion reactions of CO and isocyanide compounds
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DOI: 10.1039/b110983a
J. Chem. Soc., Perkin Trans. 1, 2002, 459–461
This journal is © The Royal Society of Chemistry 2002
459
Kang, Suk-Ku
