COMMUNICATION
Palladium-catalyzed intramolecular decarboxylative allylic arylation
of a-aryl-c-methylidene-d-valerolactonesw
Ryo Shintani,* Takaoki Tsuji, Soyoung Park and Tamio Hayashi*
Received (in Cambridge, UK) 20th November 2009, Accepted 21st January 2010
First published as an Advance Article on the web 4th February 2010
DOI: 10.1039/b924416f
A palladium-catalyzed intramolecular decarboxylative cyclization
of a-aryl-c-methylidene-d-valerolactones, followed by olefin
isomerization, has been developed to give fused polycyclic
aromatic compounds under mild conditions. The process
described here can be regarded as a formal decarboxylative
allylic arylation without using a pre-formed organometallic
nucleophile. The reaction can be conducted on a gram scale
and the products thus obtained are further derivatized with ease.
ð1Þ
ð2Þ
Transition metal-catalyzed carbon–carbon bond formation
represents a powerful strategy for efficient construction of organic
compounds. Development of a new mode of C–C bond-forming
catalysis is therefore an important objective and can open up new
ways of molecular assembly in synthetic organic chemistry. In this
regard, we recently devised g-methylidene-d-valerolactones as
new reagents for palladium-catalyzed decarboxylative addition/
cyclization reactions with several reaction partners such as 1,3-
dipoles,1a electron-deficient olefins,1b isocyanates,1c and others1d–g
As shown in Table 1, the substrate scope of the present catalysis
is fairly broad. The same transformation efficiently occurs with
to generate corresponding 5–7-membered carbo- and hetero-
cycles. Herein we describe a new usage of these reagents: a-aryl-
g-methylidene-d-valerolactones undergo a palladium-catalyzed
intramolecular decarboxylative cyclization–olefin isomerization
sequence to provide fused polycyclic aromatic compounds under
mild conditions.
other
5-membered
heteroaromatics
such
as
3-indolyl variant 1c (entry 1) and the ester moiety in substrates
1 can also be methyl instead of tert-butyl (entry 2). Lactones with
2-naphthyl derivatives 1e–1g are also applicable sustrates
(85–91% yield; entries 3–6), and the reaction can be conducted
with similar efficiency on a gram scale in the presence of
2 mol% catalyst (entry 4). In addition, although unsubstituted
parent phenyl group (1h) is not particularly suitable for the
a-substituent in the present reaction (19% yield; entry 7),7
electron-rich aromatic groups such as 3,5-dimethoxyphenyl (1i)
Initially, we conducted a reaction of a-(3-thienyl)-g-methyl-
idene-d-valerolactone 1a in the presence of 5 mol% of Pd(PPh3)4
as a catalyst in toluene at 30 1C, and intramolecular decarboxy-
lative cyclization with concomitant dearomatization of the thio-
phene ring was observed to give compound 2a in 92% yield
(eqn (1)). The same mode of transformation also took place with
3-furyl derivative 1b as a substrate to give product 2b in 93%
yield. These reactions presumably go through initial oxidative
addition of 1 to palladium(0), followed by decarboxylation,2,3 to
afford 1,4-zwitterionic intermediate A, which then cyclizes via
intramolecular nucleophilic attack of the 2-position of the thienyl
or furyl group to the p-allylpalladium moiety. We subsequently
found that 2a can be smoothly isomerized to rearomatized
compound 3a by treating it with alumina in toluene at room
temperature (90% yield; eqn (2)). This two-step sequence can
therefore be regarded as an intramolecular decarboxylative allylic
arylation without using a pre-formed organometallic reagent.4–6
and
3,4,5-trimethoxyphenyl
(1j)
can
be
effectively
incorporated at the a-position of substrates to give the
corresponding decarboxylative cyclization products under
similar conditions (entries 8 and 9). It is worth noting that the
present catalysis is also effective for a-alkenyl lactone 1k
to give decarboxylated cyclization product 2k in 90% yield
(eqn (3)).
ð3Þ
Department of Chemistry, Graduate School of Science,
Kyoto University, Sakyo, Kyoto 606-8502, Japan.
E-mail: shintani@kuchem.kyoto-u.ac.jp, thayashi@kuchem.kyoto-u.ac.jp;
Fax: +81-75-753-3988; Tel: +81-75-753-3983
w Electronic supplementary information (ESI) available: Experi-
mental procedures and compound characterization data. See DOI:
10.1039/b924416f
Interestingly, the use of a-phenyl lactone with methyl ester 1l
does not lead to the same type of cyclization product,
but instead, it selectively gives 8-membered decarboxylative
dimer 4 in high yield (eqn (4)). Furthermore, a-alkyl
lactone 1m undergoes a formal migration of hydride after
ꢀc
This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 1697–1699 | 1697
Shintani, Ryo
