SCHEME 1
P a lla d iu m -Ca ta lyzed Cycloa lk yla tion s of
2-Br om o-1,n -d ien es w ith Or ga n obor on ic
Acid s
Chang Ho Oh,*,† Hye Rhyan Sung,† Su J in Park,† and
Kyo Han Ahn‡
Department of Chemistry, Hanyang University,
Sungdong-Gu, Seoul 133-791, Korea, and Department of
Chemistry, Pohang University of Science and Technology,
Pohang, Kyungbook 790-784, Korea
could be reduced with a stoichiometric amount of formic
acid.6 Weinreb reported an intramolecular three-compo-
nent condensation whereby vinyl halide, alkene, and a
nitrogen nucleophile were incorporated into a cyclization
process to synthesize a diverse group of nitrogen hetero-
cycles.7 Delgado reported a similar tandem process utiliz-
ing nickel-promoted cyclization-quenching processes.8
Kibayashi reported that homoallylpalladium complexes,
formed from treatment of enynes with a catalytic system
of Pd2(dba)3CHCl3 and AcOH, underwent in situ Stille
coupling with various vinyltin reagents to give cyclized
products bearing allyl appendages.9 A process of pal-
ladium-catalyzed cyclization combined with Suzuki cou-
pling was recently reported by one of us wherein one of
the N-sulfonyl oxygens of the substrates is thought to
stabilize the alkylpalladium intermediate, thus prevent-
ing â-elimination.10 As a part of our ongoing research
focused on palladium-catalyzed carbocyclizations of enynes
or dienes, we have continued to search for a way of
trapping alkylpalladium intermediates, formed from
2-bromo-1,n-dienes,11 by external carbon nucleophiles
leading to cycloalkylated products. Herein we report the
successful palladium-catalyzed one-pot cycloalkylation of
2-bromo-1,n-dienes with various aryl- or alkenylboronic
acids 1a -f, as shown in Scheme 1.
changho@hanyang.ac.kr
Received February 27, 2002
Abstr a ct: Cascade palladium-catalyzed cycloalkylations of
2-bromo-1,n-dienes were accomplished in good to excellent
yields, where the alkylpalladium intermediates, formed via
an intramolecular Heck reaction of 2-bromo-1,n-dienes (n
) 6 or 7), were successfully cross-coupled with various
organoboronic acids. The optimal yields were achieved by
the use of cesium carbonate in ethanol with Pd(PPh3)4 as
catalyst, with 2-bromo-1,n-dienes and organoboronic acids
at concentrations of 0.2 and 0.3 M (1.5 equiv), respectively.
The development of a new process forming several
bonds in a single synthetic sequence represents an
attractive and active field of synthetic organic chemis-
try.11 Toward this end, there has been a growing interest
in the application of palladium-catalyzed processes, since
they usually proceed under mild reaction conditions and
are tolerant of many functional groups. One severe
limitation can be the facile â-elimination of the transient
alkylpalladium intermediates, unless they are trapped
rapidly. A few studies suppressing â-eliminations of
alkylpalladium intermediates by trapping with hydro-
gen,2 nitrogen,3 or carbon species4 have been reported.
The reduction of alkylpalladium intermediates by tri-
alkylsilanes is well-known.5 Recently, we found that
alkylpalladium intermediates, formed from enediynes,
Initially, we chose 2-allyl-2-(2-bromoallyl)malonic acid
diethyl ester (2a ) as a representative substrate in order
to optimize reaction conditions by varying palladium
catalysts and solvents (Table 1). This reaction was
expected to give the cyclized (but uncoupled) product 3a a
and its isomer 6a a , the (uncyclized) coupled product 4a a ,
and the desired product 5a a and its isomer 7a a .
When we subjected 2a to Ahn’s conditions10 (6:1) (entry
1), the cyclized but uncoupled product 6a a was isolated
† Hanyang University.
‡ Pohang University of Science and Technology.
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H. H. Tetrahedron Lett. 1999, 40, 1535-1538. (c) Oh, C. H.; J ung, H.
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10.1021/jo025665t CCC: $22.00 © 2002 American Chemical Society
Published on Web 09/04/2002
J . Org. Chem. 2002, 67, 7155-7157
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