a Reaction conditions: 1a (0.2 mmol,
1.0 equiv.), metal catalyst (10 mol%), ligand (12-20 mol%), base (20
mol%) at the 100 °C for 24 h. N.P. = No Product.b Yields were determined by1H NMR spectroscopy using
CH2Br2 as an internal standard.c 50 mol%
K3PO4 was added.d Isolated yield is given after chromatography.e 5 mol% (IPr)Pd(allyl)Cl was used.
With the optimal reaction condition in hand, we investigated the
substrates scope of this reaction (Scheme 2). Cyclobutanones bearing two
same aryl groups at the 3-position underwent the ring expansion reaction
smoothly, affording 2a–c in 81%–92% yields. When one of the
phenyl rings was changed to thienyl ring, the C–H bond activation
selectively occurred at more electron-rich thienyl rings instead of
phenyl ring. Cyclobutanones possessing phenyl ring and methyl group were
well suitable. Substrates with electron-donating or electron-withdrawing
groups at para or ortho -position of phenyl ring furnished
the desired products 2g–f in 42–84% yields. The phenyl ring
can be replaced with 1-naphthyl ring to give 2j in 62% yield,
wherein the C–H bond at 2-position of the naphthyl ring was activated.
Besides, the methyl group can also be replaced with ethyl and benzyl
groups as well, providing the indanones 2k–m . The
cyclobutanones bearing a hydrogen atom and a phenyl ring at the
3-position also underwent the desired transformation to offer2n–s in 30%–56% yields. Compared to the 2n ,
introducing electron-donating (2o and 2p ) or
electron-withdrawing groups (2r and 2s ) atpara -position of phenyl ring could promote the reactivity.
Interestingly, when the two substituents at 3-position are benzyl group,
the cyclobutanone would undergo ring expansion from a four-membered ring
to form a six-membered ring and gave 1-tetralone 2t in 74%
yield, which indicates the process involving C–H bond activation
occurred at the ortho -position of phenyl ring of benzyl group.
Scheme 2 Substrate scope for this reaction. Unless otherwise
specified, the reaction was performed under optimized condition:
diphenylcyclobutane 1a (0.2 mmol, 1.0 equiv.), (IPr)Pd(allyl)Cl
(0.02 mmol, 10 mol%), K3PO4 (0.1 mmol,
50 mol%) in PhMe (2 mL) at
100 °C for 24 h.a 120 °C. b 20 mol%
K3PO4 was used.
To investigate the reaction mechanism, we performed several control
experiments. 1a-d10 with two fully
deuterated phenyl rings was subjected to the standard condition and
2a-d10 was obtained in 65% yield (Scheme 3a). The deuterium atom at the
ortho-position of phenyl rings didn’t transferred to the methyl group of2a-d9 , which isn’t consistent with the
previous Rh-catalytic system. Therefore, the pathway involving
intramolecular C–C/C–H σ-bond metathesis could be excluded. Next, we
performed the reaction in the presence of D2O, the
mixture of four products was
obtained in 75% total yield (Scheme 3b). It indicates that the reaction
may undergo protodemetalation process, the proton on methyl comes from
the reaction system. The
competition experiment was also
conducted between 1a and 1a-d10(Schem 3c). This weak kinetic isotope effect implied that C‒H activation
might be not the rate-determining step. It is worth mentioning that when
cutting the reaction time to 5 h, no product was detected. It might can
attribute to the need of a long induction period for C−C bond cleavage.
Scheme 3 Mechanistic
experiments.
On the basis of deuterization experiments and litereature’s reports, we
propose that the reaction is initiated by the oxidative C–C bond
cleavage of clobutenone 1a to give a five-membered palladacycleA , which would undergo an intramolecular electrophilic C‒H
activation to give bridged bicyclic intermediate B . Subsequent
facile C(sp2)-C(sp2) reductive
elimination gives the alkylpalladium species C , followed by
protodemetalation to deliver the final product 2 .
Scheme 4 Proposed catalytic cycle.
Conclusions
In conclusion, this work for the first time demonstrates that
Pd-catalyst is also capable of cleavage of C(carbonyl)−C bonds of
cyclobutanones via oxidative addition, which would provide chance to
find new transformations based on cyclobutanones. According to
Pd-catalyzed condition, we realized the skeletal reorganisation of
cyclobutanones invoving successive cleavage of C(carbonyl)−C bonds and
C−H bond cleavage, delivering diverse indanones. In contrast to the
previous Rh-catalytic system, the Pd-catalytic system herein involves
different mechanism and features several advantages: 1) no need of
directing group to facilitate the C(carbonyl)−C bond cleavage; 2) much
milder reaction condition and 3) simplified work-up.
Experimental
General procedure for Palladium-catalyzed skeletal reorganisation of
cyclobutanones: In an N2-filled glovebox, an oven-dried
25-mL Schlenk tube equipped with a Teflon-coated magnetic stir bar was
charged successively with (IPr)Pd(allyl)Cl (11.4 mg, 0.02 mmol, 10
mol%), K3PO4 (21.2 mg, 0.1 mmol, 0.5
equiv.), cyclobutanones 1 (0.2 mmol, 1.0 equiv. If the compound
is an oil, then it will be injected into the reaction after adding the
solvent) and PhMe (2 mL). The tube then was sealed with a Teflon screw
cap, moved out of the glovebox, and reacted at the assigned temperature
with vigorous stirring. After 24 h, the reaction mixture was cooled to
room temperature, and the solvent was evaporated under vacuum to give
the crude product. The resulting residue was purified by silica gel
flash column chromatography to afford the corresponding indanones2 .
Supporting Information
The supporting information for this article is available on the WWW
under https://doi.org/10.1002/cjoc.2021xxxxx.
Acknowledgement
We thank the National Natural Science Foundation of China (22071114,
22022103, and 21871146), the Haihe Laboratory of Sustainable Chemical
Transformations, the National Key Research and Development Program of
China (2019YFA0210500; 2020YFA0711504), and “Frontiers Science Center
for New Organic Matter,” Nankai University (63181206) for their
financial support. We also thank Jiting Cui and Di Wang from Zhejiang
University for assisting us on the TA spectra measurement. Ke Gao and
Yanna Sun thank the National Natural Science Foundation of China
(52103221and 52172048), and Shandong Provincial Natural Science Foundation
(ZR2021QB179andZR2021ZD06),
the National Key Research and Development Program of China
(2022YFB4200400) funded by MOST and the Fundamental Research Funds of
Shandong University. Finally, we thank the staff of beamlines BL17B1,
BL19U, and BL01B1 at SSRF for providing the beam time and User
Experiment Assist System of SSRF for their help. Yingguo Yang thanks the
National Natural Science Foundation of China (12175298).
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