Vinylboron Self-Promoted Carbonylative Coupling with Cyclobutanone Oxime Esters

Article abstract of DOI:10.1021/acs.orglett.9b00333

Despite the significant progress that has been made in the area of catalyst-dependent chemistry, the exploration of a greener and more environmentally benign catalyst-free reaction remains one of the most important areas in modern chemistry. Herein, we present a vinylboron self-promoted carbonylative coupling with cyclobutanone oxime esters. Various cyclobutanone oxime esters and substituted styrylboronic acids can be transformed into the corresponding enones in moderate to good yields. Detailed EPR investigations and control experiments provide sufficient evidence to show that this reaction goes through a single-electron transfer process.

Full text of DOI:10.1021/acs.orglett.9b00333

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Vinylboron Self-Promoted Carbonylative Coupling with
Cyclobutanone Oxime Esters
̈
Zhiping Yin, Jabor Rabeah, Angelika Bruckner, and Xiao-Feng Wu*
Leibniz-Institut fur Katalyse e.V. an der Universitat Rostock, Albert-Einstein-Straße 29a, 18059 Rostock, Germany
̈
̈
S
* Supporting Information
ABSTRACT: Despite the significant progress that has been made in
the area of catalyst-dependent chemistry, the exploration of a greener
and more environmentally benign catalyst-free reaction remains one
of the most important areas in modern chemistry. Herein, we present
a vinylboron self-promoted carbonylative coupling with cyclo-
butanone oxime esters. Various cyclobutanone oxime esters and
substituted styrylboronic acids can be transformed into the corresponding enones in moderate to good yields. Detailed EPR
investigations and control experiments provide sufficient evidence to show that this reaction goes through a single-electron
transfer process.
ver the past decades, the concept of green chemistry has
aroused a greater awareness and interest in academic and
Scheme 1. Methodologies for the Coupling of
Cyclobutanone Oxime Esters with Styrylboronic Acids
O
industry researchers since it meets environmental and
economic goals.1 Impressive progress has been achieved in
various research areas, such as the exploration for a greener
and more sustainable process, and the design of safer chemicals
and environmentally friendly feedstocks. Recently, investiga-
tions into catalyst-free reactions2 have attracted broad
attention among chemists as well. In general, the catalyst is a
crucial factor for a reaction, which can promote faster chemical
reactions, and better selectivity also can be obtained by using
special catalysts or reagents. Although avoiding the use of a
catalyst is a highly challenging task, many elegant works were
established by different groups since the earliest example of
cycloaddition reaction between furan and maleic anhydride in
water without any catalyst was reported in 1931.3
On the other hand, carbonylation reactions are widely used
in both large and small scales for the production of fine and
bulk chemicals, which provide an efficient method for
introducing a synthetically useful carbonyl group into their
parent molecules. Recently, our group disclosed a series of
nitrogen-centered radicals mediated carbonylation reactions.
These nitrogen radicals were generated from the transition-
metal-catalyzed cleavage of N-halogen bonds and then
captured by CO gas to give the corresponding carbonyl-
containing products.4 Besides, cyclobutanone oxime esters as a
good precursor for generating an iminyl radical received
considerable attention over the years. Different kinds of
transition metals, such as rhodium,5 palladium,6 nickel,7 iron,8
copper,9 and photocatalysts,10 have been successfully used for
the activation of these compounds (Scheme 1). However, the
direct carbonylative coupling of cyclobutanone oxime esters in
the absence of catalyst or light remains unknown in
literature.11
styrylboronic acid were selected as the model substrates to test
our hypotheses. To our delight, after screening various reaction
conditions, we found that the best results can be obtained in
DMAc/H2O (10:1) at 120 °C under 50 bar of CO in the
absence of any additional catalyst, which produced the desired
α,β-unsaturated ketone in 61% isolated yield (for details on
optimization of the reaction conditions; see Supporting
Information).
To gain deeper knowledge regarding the reaction mecha-
nism, the reaction between 1a and 2a was investigated by in
situ electron paramagnetic resonance (EPR) in the presence
and absence of 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a
spin trap to detect the short-lived radicals which might be
formed during the course of the reaction. In the absence of
DMPO, the EPR spectrum of the reaction mixture containing
1a and 2a in CH3CN at 77 °C shows no signal even after
heating the solution for 30 min. However, in the presence of
DMPO, the EPR spectrum shows a six-line signal at g = 2.007
with AN = 13.6 G and AβH = 19.6 G (Figure 1) characteristic
of a DMPO-R spin adduct. A similar EPR signal was observed
when only 2a was heated at 77 °C in CH3CN in the presence
of DMPO suggesting that the catalytic reaction might be
initiated by the formation of a new radical from 2a. Then the
Based on these backgrounds, we turned our attention toward
exploring the possibility of a catalyst-free carbonylation
reaction. Initially, cyclobutanone O-benzoyl oxime and trans-
Received: January 26, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b00333
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Letter
experiments a−c, and only an 8% GC yield was obtained in
the control experiment d. Then the reaction was conducted
with 1.5 equiv of TEMPO under standard conditions, which
completely inhibited the reaction to form product 3a. The
alkylated TEMPO product was formed in 54% isolated yield.
Finally, (E)-(2-(4-chlorostyryl)-4,5,5-trimethyl-1,3,2-dioxabor-
olan-4-yl)methylium 2h was selected to react with 1a under
the standard conditions. This reaction proceeded smoothly
and gave the corresponding product 3d in 35% isolated yield.
Moreover, (E)-6-phenylhex-5-enenitrile can be obtained in the
absence of carbon monoxide (Scheme 2g).
Based on the results of control experiments and EPR results,
we proposed a possible reaction mechanism, shown in Scheme
3. Initially, promoted by 2a and DMAc, an iminyl radical A was
Scheme 3. Proposed Mechanism
Figure 1. EPR spectra before (black line) and after addition of
DMPO to reaction EPR 1 measured at 20 °C after heating the
mixture at 77 °C for 30 min.
reaction of the new radical with 1a leads to generation of an
iminyl radical intermediate which is also a carbon-centered
radical. For this reason, we cannot distinguish the radical type
between 2a and EPR 1 reaction by EPR since both of them
lead to the formation of DMPO-R spin adducts.
Furthermore, several control experiments were conducted to
further understand the reaction mechanism. As shown in
Scheme 2, styrene was used to replace the trans-styrylboronic
acid 2a as substrates, and a 20 mol % boron source including
PhB(OH)2, bis(pinacolato)diboron ((Bpin)2), BF3·Et2O, and
2a were added into reaction mixtures as the catalyst. However,
no desired product 3a was detected in these control
generated from 1a. Subsequently, the iminyl radical A goes
through a ring-opening process to produce a highly reactive
cyanoalkyl radical B, which will be trapped by CO to give
intermediate C. Addition of the acyl radical C to trans-
styrylboronic acid forms a new benzyl radical D. Finally,
intermediate D will be transformed into the desired α,β-
unsaturated ketone 3a after reaction with substrate 1a.
Scheme 2. Control Experiments
With the optimized reaction conditions in hand, we next
evaluated the substrate scope of this reaction with a range of
cyclobutanone oxime esters and (E)-styrylboronic acid
derivatives. As shown in Table 1, various substituted
styrylboronic acids worked well under the standard conditions.
Electron-withdrawing groups such as fluorine, chloride, and
trifluoromethyl at the para position of the aromatic ring led to
the corresponding α,β-unsaturated ketones in moderate yields
(Table 1, 3b−3d). In addition, electron-donating groups at the
para position also proceed smoothly under the standard
conditions and deliver the desired products in moderate to
good yield (Table 1, 3e−3g). The substrate bearing a para
methyl group gives the ketone product in 75% yield (Table 1,
3f). However, in the cases of α-vinylboron and alkyl
vinylboron such as (1-phenylvinyl)boronic acid and (E)-(2-
cyclohexylvinyl)boronic acid, no desired product could be
detected and substrates decomposed. Subsequently, cyclo-
butanone oxime esters with various functional groups including
phenyl, benzyl, octanoyl, and ester were tested and the
corresponding products were obtained in moderate yields
(Table 1, 3h−3k). Disubstituted cyclobutanone oxime ester
also engaged in this reaction smoothly, leading to the desired
products in 45% and 47% yields respectively (Table 1, 3l, 3m).
It should be noted that the Boc-protected piperidine derivative
showed comparable reactivity and formed the desired α,β-
unsaturated ketone in 40% yield (Table 1, 3n). Finally,
nonsymmetrical cyclobutanone oxime ester derivatives deliv-
ered the corresponding α,β-unsaturated ketones in 33% and
B
DOI: 10.1021/acs.orglett.9b00333
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Letter
Table 1. Scope of Vinylboron Self-Catalyzed
Carbonylation
Table 1. continued
a
b
bar of CO; isolated yields. 1 mmol scale: 1a (1 mmol, 1.0 equiv), 2a
(1.2 mmol, 1.2 equiv) in 5.5 mL of DMAc/H2O (10:1) at 120 °C for
20 h, under 50 bar of CO; isolated yields.
20% yields, in which C−C bond cleavage occurred selectively
at the more hindered position (Table 1, 3o, 3p). However, no
desired product could be detected when cyclopentanone or
cyclohexanone oxime esters were tested with styrylboronic acid
under our standard conditions.
In summary, a new method for the synthesis of diverse
cyano-containing α,β-unsaturated ketone products has been
established. The reaction was conducted in DMAc/H2O in the
absence of any additional catalyst. Various cyclobutanone
oxime esters and substituted styrylboronic acids can be
converted into the corresponding products in moderate to
good yields. In addition, EPR investigations and control
experiments also clearly showed that this reaction goes through
a single-electron transfer pathway.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b00333.
General comments, general procedure, optimization
details, analytic data and NMR spectra (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: xiao-feng.wu@catalysis.de.
ORCID
Zhiping Yin: 0000-0002-4296-8824
Angelika Bruckner: 0000-0003-4647-1273
̈
Xiao-Feng Wu: 0000-0001-6622-3328
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the analytical department of Leibniz-Institute for
Catalysis at the University of Rostock for their excellent
analytical service. We also appreciate the general support from
̈
Professor Armin Borner and Professor Matthias Beller in
LIKAT.
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