Carbonylative Mizoroki-Heck Reaction of Alkyl Iodides with Arylalkenes Using a Pd/Photoirradiation System

Article abstract of DOI:10.1021/acs.orglett.5b02302

A carbonylative Mizoroki-Heck reaction using alkyl iodides was achieved with a Pd/photoirradiation system using DBU as a base. In this reaction, alkyl radicals were formed from alkyl iodides via single-electron transfer (SET) and then underwent a sequential addition to CO and alkenes to give β-keto radicals. It is proposed that DBU would abstract a proton α to carbonyl to form radical anions, giving α,β-unsaturated ketones via SET.

Full text of DOI:10.1021/acs.orglett.5b02302

Letter
pubs.acs.org/OrgLett
Carbonylative Mizoroki−Heck Reaction of Alkyl Iodides with
Arylalkenes Using a Pd/Photoirradiation System
Shuhei Sumino, Takahito Ui, Yuki Hamada, Takahide Fukuyama, and Ilhyong Ryu*
Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan
S
* Supporting Information
ABSTRACT: A carbonylative Mizoroki−Heck reaction using alkyl iodides
was achieved with a Pd/photoirradiation system using DBU as a base. In this
reaction, alkyl radicals were formed from alkyl iodides via single-electron
transfer (SET) and then underwent a sequential addition to CO and alkenes to give β-keto radicals. It is proposed that DBU
would abstract a proton α to carbonyl to form radical anions, giving α,β-unsaturated ketones via SET.
arbonylative cross-coupling reactions of organic halides
have found wide applications in organic synthesis since
Pd catalyst under thermal conditions.10 To the best of our
knowledge, however, the present study is the first report on the
intermolecular processing of alkyl halides.
We first attempted the reaction of iodocyclohexane 1a or 1-
iodoadamantane 1b and styrene 2a as a model reaction (Table
1). When a mixture of 1a or 1b, 2a, K2CO3, and a catalytic
amount of Pd(PPh3)4 was irradiated using a xenon lamp (500 W)
C
they provide straightforward access to a variety of carbonyl
compounds.1 In the carbonylative Mizoroki-Heck reaction that
leads to a,b-unsaturated ketones,2 aryl and vinyl halides are the
most suitable substrates, but the reaction limits the use of alkyl
halides3 due to the instability of key alkyl Pd species, which allow
isomerization via facile β-Pd−H elimination.4,5
In contrast to the alkyl Pd species, alkyl radicals are sufficiently
stable to isomerization. Thus, we were interested in developing a
cooperative reaction system wherein both radical species and
organometallic species could work cooperatively so as to clear
the substrate limitations.6 Consequently, we developed a series of
Pd/light-induced cascade carbonylation reactions wherein alkyl
radicals would act as transient radicals and in the end
carbonylation would give acyl radicals, which could be
transformed to acylpalladium species.7 The Pd/light system
has been effective for carbonylative Sonogashira reaction8 and
carbonylative Suzuki−Miyaura reaction9 of alkyl iodides
(Scheme 1, eqs 1 and 2). We report herein that the carbonylative
Mizoroki−Heck reaction of alkyl iodides with arylalkenes
proceeded well using a Pd/light system with DBU as a base
(Scheme 1, eq 3). Alexanian and co-workers recently reported an
intramolecular carbonylative Mizoroki−Heck reaction using a
a
Table 1. Optimization of the Reaction Conditions
Scheme 1. Carbonylative Cross-Coupling Reactions of Alkyl
Iodides using a Pd/Light System
a
Reaction conditions: 1a or 1b (0.3 mmol), Pd(PPh3)4 (5 mol %),
base (2 equiv), styrene [2 equiv (For entries 8 and 10 are 10 equiv)],
b
solvent (8 mL), CO (45 atm), 16 h. DABCO: 1,4-
diazabicyclo[2.2.2]octane. TMG: 1,1,3,3-tetramethylguanidine.
MTBD: 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene. DBU: 1,8-
c
d
diazabicyclo[5.4.0]undec-7-ene. BTF: benzotrifluoride. GC yields.
e
Conducted under thermal conditions (120 °C).
Received: August 8, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b02302
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through a Pyrex filter under 45 atm of CO, no carbonylative
Mizoroki−Heck reaction took place (Table 1, entries 1 and 2).
Then, after amine bases were screened for the reaction of 1b
(Table 1, entries 3−7), we were pleased to find that the addition
of DBU gave 60% yield of the desired product 3b (Table 1, entry
7). Changing toluene to the more-polar BTF (benzotrifluor-
ide)11 improved the yield of 3b to 67% (Table 1, entry 10). A
similar tendency of this solvent effect was observed in the
conversion of 1a to 3a (Table 1, entries 8 and 9). The reaction of
1a with 2a under thermal conditions (120 °C) did not give 3a
(Table 1, entry 11). Interestingly, however, a photoirradiation
reaction in the absence of palladium catalyst but with DBU gave
3a, albeit in a low yield (Table 1, entry 12). The reaction in the
presence of Mn2(CO)1012 instead of Pd(PPh3)4 gave 3a, but the
efficiency was inferior to using the Pd catalyst (Table 1, entry 13).
PtCl2(PPh3)2 gave a result comparable to that for palladium
catalyst (Table 1, entry 14). On the other hand, Fe3(CO)12 and
NiCl2(PPh3)2 did not work in this reaction system (Table 1,
entries 15 and 16). In all cases examined, noncarbonylative
Mizoroki−Heck reaction products were not observed, whereas
byproducts via the second addition to the product enones are
often formed.
Table 2. Carbonylative Mizoroki−Heck Reaction Using Alkyl
a
Iodides 1 and Alkenes 2
Using the conditions of entry 9 or 10 in Table 1, we then
examined the generality of the carbonylative Mizoroki−Heck
reaction for a variety of alkyl iodides and alkenes, and the results
are summarized in Table 2. The reactions of primary and
secondary alkyl iodides 1c and 1d with 2a gave the
corresponding α,β-unsaturated ketones 3c and 3d in moderate
to good yields (Table 2, entries 3 and 4). The reaction of 2-
iodoindane 1e with 2a gave an enone 3e in 40% yield (Table 2,
entry 5). Functionalized Iodoalkanes with chlorine or ester
moieties, 1f and 1g, also proceeded to give the corresponding
enones 3f and 3g (Table 2, entries 6 and 7). A variety of
arylalkenes also participated in the present reaction (Table 2,
entries 8−16). For example, 1a reacted with o-, m-, and p-
methylstyrene (2b, 2c, and 2d) to give the corresponding α,β-
unsaturated ketones 3h, 3i, and 3j, respectively (Table 2, entries
8−10). Styrenes with an electron-withdrawing group also
participated in the present reaction. Thus, the reaction of 1a
with p-CF3-substituted styrene 2e gave 3k in 59% yield (Table 2,
entry 11). The reaction of 1a with p-fluoro-substituted styrene 2f
gave 3l in 54% yield (Table 2, entry 12). In the case of p-bromo-
substituted styrene 2g, the reaction gave the corresponding
enone 3m, with the carbon−bromine bond remaining intact
(Table 2, entry 13). 2-Vinylnaphthalene 2h and 1,1-diphenyl-
ethylene 2i were also acceptable and gave the corresponding
products 3n and 3o (Table 2, entries 14 and 15). On the other
hand, the reaction of 1a with 2-vinylthiophene 2j gave enone 3p
in a low yield (Table 2, entry 16). We also examined the reaction
of 1b with ethyl acrylate 2k, and it gave the product 3q in a low
yield (Table 2, entry 17).
To understand the role of radical species in this carbonylative
Mizoroki−Heck reaction, we examined the reaction of
(iodomethyl)cyclopropane 1h, CO, and 2a (Scheme 2). The
reaction gave 3-butenyl styryl ketone 3r in 53% yield with no
trace of cyclopropylcarbinyl ketone 3s. This suggests that in this
system a cyclopropylcarbinyl radical forms and undergoes quick
isomerization to a homoallyl radical.13
a
Reaction conditions: 1 (0.3 mmol), CO (45 atm), 2 (3 mmol),
Pd(PPh3)4 (5 mol %), DBU (2 equiv), BTF (benzotrifluoride) (8
mL), hν (xenon lamp, Pyrex), 16 h. 2k (2 equiv).
b
We checked into whether the E/Z geometry of the enones
changes under photoirradiation. When the isolated E-3a or Z-3a
was irradiated with no reagents, both E and Z forms of 3a were
isomerized to another isomer, giving the same E/Z ratio (Scheme
3). Upon further heating of the E/Z mixture of 3a under dark
conditions at 80 °C for 16 h, only E-3a was obtained.
B
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Scheme 2. Carbonylative Mizoroki−Heck Reaction Using
(Iodomethyl)cyclopropane 1h
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.5b02302.
Detailed experimental procedures and spectroscopic data
(PDF)
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: ryu@c.s.osakafu-u.ac.jp.
Notes
Scheme 3. Isomerization of 3a under Photoirradiation
Conditions
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by a Grant-in-Aid for Scientific
Research from the JSPS and MEXT. S.S. acknowledges a
Research Fellowship of the JSPS for Young Scientists.
REFERENCES
■
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