Cascade radical reactions catalyzed by a Pd/light system: Cyclizative multiple carbonylation of 4-alkenyl iodides

Article abstract of DOI:10.1021/ja017315e

Cascade reactions of 4-alkenyl iodides, involving a carbonylation-cyclization-carbonylation sequence, were accomplished by a hν/Pd system. The stereochemical outcomes suggest that radical carbonylation and subsequent acyl radical cyclization may be involv

Full text of DOI:10.1021/ja017315e

Published on Web 03/22/2002
Cascade Radical Reactions Catalyzed by a Pd/Light System: Cyclizative
Multiple Carbonylation of 4-Alkenyl Iodides
Ilhyong Ryu,*,† Sergio Kreimerman, Fumikazu Araki, Satoshi Nishitani,† Yoji Oderaotoshi,
Satoshi Minakata, and Mitsuo Komatsu*
Department of Chemistry, Faculty of Arts and Sciences, Osaka Prefecture UniVersity,
Sakai, Osaka 599-8531, Japan, and Department of Applied Chemistry,
Graduate School of Engineering, Osaka UniVersity, Suita, Osaka 565-0871, Japan
Received October 17, 2001
Chart 1
Bond-forming reactions that include cascade steps have gained
increasing significance as versatile synthetic methods.1 Herein we
report new cascade reactions, in which five-membered cyclic keto
esters and amides are prepared starting from 4-alkenyl iodides via
cyclizative multiple CO-trapping reactions (Chart 1). For this
purpose, we employed a radical/metal hybrid strategy that relies
Scheme 1
upon both radical cascades2,3 and palladium catalysis. Related
cascade transformations including a carbonylation-cyclization-
carbonylation sequence have been reported by the Negishi group,4
and the Grigg group,5 by taking advantage of the reactivity of
palladium catalysts with properly substituted aromatic and Vinylic
halides.6 Unfortunately, palladium-catalyzed transformations are not
applicable to the wider class of aliphatic halides, due to the low
reactivity of sp3-carbon-halogen bonds toward oxidative addition
with Pd.7,8 We believe that the present hybrid strategy provides a
viable solution to this problem.
as the major products along with the doubly carbonylated γ-keto
amides 3 (runs 13-15). Although the formation of vicinal keto
amides has many precedents in palladium-catalyzed double carbo-
nylation chemistry,12 most of them are for aryl, benzyl, vinyl, and
allyl halides and we are aware of only two cases with respect to
alkyl halides.12a,c
We initially examined the possibility of applying atom transfer
carbonylation9 to the envisaged cascade reaction. When 4-pentenyl
iodide (1a) was exposed to standard reaction conditions (irradiation
with a xenon lamp through Pyrex under 40 atm of CO pressure),9a
the desired cyclic keto ester 2a was indeed formed, but the yield
was only 5% (Scheme 1). It is conceivable that, unlike the case of
simple ester synthesis,9a the ionic termination reaction may not be
efficient enough to shift the five equilibrium steps (homolysis,
carbonylation, cyclization, carbonylation, and iodine atom transfer)
to completion. Then, we examined the palladium-catalyzed carbo-
nylation of 1a under thermal conditions using Pd(PPh3)4, but as
anticipated, there was no reaction. Interestingly, however, when
these two conditions, irradiation and treatment with Pd(0) catalyst,
are employed together, the desired keto ester 2a was obtained in a
remarkable 61% yield.10 The tuning of the conditions by addition
of 4-(dimethylamino)pyridine (DMAP) improved the yield up to
82%.
As shown in Table 1, the present cyclizative double carbonylation
sequence is applicable to a wide variety of 4-alkenyl iodides having
sp3-carbon-iodine bonds. 4-Pentenyl bromide (1a′) can also be
used, but the yield of 2a′ was rather modest. A spirocyclic keto
ester 2c was formed from 1c. Secondary substrates 1d, 1e, 1f, and
1g also worked well to give the corresponding cyclic keto esters
2d, 2e, 2f, and 2g in good yields. The cyclizative double
carbonylation of 1h and 1i proceeded stereoselectively to give the
corresponding bicyclic keto esters 2h and 2i, whose pendant
methoxycarbonyl group was disposed on the convex face.11
The cyclizative carbonylation, when performed in the presence
of diethylamine, provided triply carbonylated R,δ-diketo amides 4
The cascade reactions that we have observed clearly result from
the interplay of two reactive species, radicals and organopalladium
species. To determine whether the Pd(0)/hν system would effect
initiation of radical reactions in our system,13 we examined the
atom-transfer cyclization of 1-ethyl-5-hexenyl iodide and found that
the presence of Pd resulted in a much more efficient reaction and
that the observed cis/trans ratio (72/28) of the product, 1-ethyl-2-
(iodomethyl)cyclopentane, was identical with that observed for a
1-methyl-5-hexenyl radical cyclization.14 In addition, the observed
stereochemical outcomes for the cyclizations of 1e and 1f (cis/
trans ) 43/57 and 38/62, respectively) are identical to those obtained
in the tin radical-mediated carbonylation of the same substrates,2a
providing support for the postulate that a 5-exo-trig acyl radical
cyclization of B leading to C does occur in the present reaction
system (Scheme 2). On the other hand, the formation of esters,
amides, and keto amides, should be considered to be the products
of acylpalladium intermediates. One possibility is that the acyl
radical D, arising from the second carbonylation, undergoes
coupling with Pd(I) to give an acylpalladium intermediate E, which
may be the precursor for the final product 2.15 Mechanistic aspects
of palladium-catalyzed single and double carbonylation of organic
halides have been extensively investigated.16 On the basis of the
arguments previously advanced by the Yamamoto group and in
analogy to the corresponding reactions of double carbonylation of
benzyl chloride,16b we propose that (4-oxo-acyl)(carbamoyl)-
palladium complexes would be formed in our system, serving as
the key precursors for R-keto amides 4 via reductive elimination.
* To whom correspondence should be addressed. E-mail: ryu@
ms.cias.osakafu-u.ac.jp.
† Osaka Prefecture University.
9
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J. AM. CHEM. SOC. 2002, 124, 3812-3813
10.1021/ja017315e CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Pd/Light-Induced Cyclizative Carbonylation Reactions
of 1a
Nagase Science Foundation. We thank Dr. Cathleen M. Crudden
and Dr. Vladimir Grushin for useful discussions.
Supporting Information Available: Typical experimental proce-
dure and spectroscopy data and analytical data of all products (PDF).
This material is available free of charge via the Internet at http//
pubs.acs.org.
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Scheme 2
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Acknowledgment. Dedicated to Professor Howard Alper on
the occasion of his 60th birthday. This research was supported by
a Grant-in-Aid for Scientific Research from the Ministry of
Education, Culture, Sports, Science, and Technology, Japan and
JA017315E
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