A denitrogenative palladium-catalyzed cascade for regioselective synthesis of fluorenes

Article abstract of DOI:10.1039/c9sc04062e

We herein report a denitrogenative palladium-catalyzed cascade for the modular and regioselective synthesis of polysubstituted fluorenes. Hydrazone facilitates the Pd(ii) to Pd(iv) oxidative addition in a Catellani pathway and is also the methylene synthon in the proposed reaction. Aryl iodides and 2-bromoarylaldehyde hydrazones undergo a norbornene-controlled tandem reaction sequence to give a broad scope of fluorenes in the presence of a palladium catalyst. The method described is scalable and adaptable to a three-component reaction with in situ generation of the hydrazone group. Preliminary mechanistic investigations have been conducted.

Full text of DOI:10.1039/c9sc04062e

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A denitrogenative palladium-catalyzed cascade for
regioselective synthesis of fluorenes†
Cite this: DOI: 10.1039/c9sc04062e
*
All publication charges for this article
have been paid for by the Royal Society
of Chemistry
Wai Chung Fu ‡ and Fuk Yee Kwong
We herein report a denitrogenative palladium-catalyzed cascade for the modular and regioselective
synthesis of polysubstituted fluorenes. Hydrazone facilitates the Pd(II) to Pd(IV) oxidative addition in
a Catellani pathway and is also the methylene synthon in the proposed reaction. Aryl iodides and 2-
bromoarylaldehyde hydrazones undergo a norbornene-controlled tandem reaction sequence to give
a broad scope of fluorenes in the presence of a palladium catalyst. The method described is scalable and
adaptable to a three-component reaction with in situ generation of the hydrazone group. Preliminary
mechanistic investigations have been conducted.
Received 14th August 2019
Accepted 17th December 2019
DOI: 10.1039/c9sc04062e
rsc.li/chemical-science
demonstrated the utilization of a deciduous carboxyl group16 to
facilitate the Pd(II)/(IV) oxidative addition in Catellani-type
aromatic p-extension reactions (Fig. 1B).17 As part of our
Introduction
Regioselective functionalization of organic molecules is one of
the most important, yet challenging objectives in modern
synthetic organic chemistry.1 In this regard, the Catellani
reaction, which was discovered by the Catellani group in 1997,2
is a powerful and versatile tool for constructing polysubstituted
arenes in a regioselective fashion via palladium/norbornene
cooperative catalysis.3 The transformation is a tandem difunc-
tionalization of aryl iodides which installs nucleophile ([E]-X)
and electrophile ([Nu]-Y) at both ipso- and ortho-positions
(Fig. 1A).2,3 Aer 20 years of advancements, a large number of
chemical transformations have been successfully incorporated
into the Catellani reaction manifold, which includes Mizoroki–
Heck reaction,2,4 Sonogashira coupling,5 Suzuki coupling,6
enolate coupling,7 amination,8 borylation,9 cyanation,10 direct
C–H arylation,11 thiolation12 and others.13 Recent contributions
in this eld have also revealed that Catellani-type reactions can
be initiated by Pd(II) species with starting materials other than
aryl iodides.14 Amongst the Pd(0) or Pd(II)-initiated Catellani
cycles, directing/chelating groups were oen used to facilitate
the Pd(II)–Pd(IV) oxidative addition or to affect selective arene
C–H activation.15 Nevertheless, these assisting groups oen
remain in the product structure and may not always be
a subsequent synthetic handle for future derivatizations. In
order to address this pitfall, our group have recently
Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The Chinese
University of Hong Kong, Shatin, New Territories, Hong Kong. E-mail: fykwong@
cuhk.edu.hk
† Electronic supplementary information (ESI) available: Detailed experimental
procedures, 1H, 13C NMR spectra, and characterization data of all new
compounds. CCDC 1833356. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c9sc04062e
Fig. 1 (A) A typical Catellani reaction; (B) previous work: decarbox-
ylative aromatic p-extension reactions; (C) hydrazone as a directing
group in Ir-catalyzed C–H borylations; (d) this work: Pd-catalyzed
norbornene-mediated denitrogenative synthesis of fluorenes.
‡ Present address: Department of Chemistry, Massachusetts Institute of
Technology 77 Massachusetts Avenue, Cambridge, MA 02139 (USA).
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Fig. 2 Approaches and difficulties of fluorene syntheses; (A) traditional multistep synthesis of fluorenes; (B) Pd-catalyzed tandem or intra-
molecular synthesis of fluorenes; (C) lack of directing abilities of methylene group in fluorene.
continuing efforts in Pd/norbornene chemistry, we aim to iodotoluene has given uorene 3a in 38% yield in the presence
explore new methods to access other chemical classes. Hydra- of a Pd(OAc)2/PPh3 catalyst and norbornene (Table 1, entry 1).
zones have been reported to be a useful directing group in Pd-, An optimization study of reaction parameters was then under-
Rh- or Ir-catalyzed reactions (Fig. 1C),18 and we sought to adopt taken with a survey of phosphine ligands, solvents bases and
it as an assisting group to facilitate the heterobiaryl formation stoichiometry of reagents. Selected entries of our optimization
in the Catellani cycle. During our investigations, we found that have been shown in Table 1 (please see Tables S1–S3 in ESI† for
aryl iodides reacted with 2-bromoarylaldehyde hydrazone to detailed optimization data). Amongst the trialkyl or triaryl
give uorenes under typical Catellani reaction conditions.
Herein we report the development and results of a novel deni-
trogenative palladium-catalyzed cascade for the modular and
regioselective synthesis of uorenes (Fig. 1D).
Table 1 Selected entries for reaction optimizationa
Although uorene and its derivatives are ubiquitous structural
motifs in light-emitting optoelectronics,19 organic semi-
conductors,20 nanostructures,21 functional polymers,20c,22 chemo-
sensors19a,23 and bioactive compounds,24 we identied a multitude
of challenges on their syntheses based on literature precedents.
Traditional synthesis of substituted uorenes mostly rely on the
post-functionalization of 9H-uorene via lengthy sequences
(Fig. 2A),20a while transition metal-catalyzed reactions have also
been developed to efficiently prepare uorenes in one pot
(Fig. 2B).25 Construction of the methylene group employs intra-
molecular direct C sp3–H activation or cleavage of a C sp3–X bond,
but these biaryl substrates require pre-activation and inherently
offset the methods' accessibility and scope.20c,26 These pre-
functionalized substrates are typically prepared in multiple
synthetic steps and the C9 (methylene) position is oen substituted
with functional groups, which cannot be readily converted into
other moieties, such as alkyl chains that are important for liquid
crystal formation.19a,27 Recently, impressive carbenoid cross-
coupling strategies have been disclosed by the groups of Wang, 15d
Hu and others.28 However, the formation of regioisomers was still
possible due to the unselective oxidative addition of C–Br/Cl bond
and C–H activation. Although cross-dehydrogenative coupling
(CDC) is useful in the preparation of heterocycles (Fig. 2C),29 it is not
applicable for accessing uorenes owing to the lack of directing
abilities of the methylene group in the diarylmethane scaffold.
Entry
Ligand
Base
Solvent
% Yieldb
1
2
3
4
5
6
PPh3
PCy3
PCyPh2
P(4-OMeC6H4)3
cataCXium A
XPhos
PPh2-DavePhos
DPPF
PCyPh2
PCyPh2
PCyPh2
PCyPh2
PCyPh2
PCyPh2
PCyPh2
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
Na2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
DMF
38
57
74
43
13
37
45
31
73
5
80
78
76
35
0
7
8c
9
10
11
12
13
14
NMP
1,4-Dioxane
CH3CN
DMF
a
Reaction conditions: Pd(OAc)2 (10 mol%), ligand (25 mol%), 2-
iodotoluene (0.2 mmol), (2-bromobenzylidene)hydrazine (0.24 mmol),
norbornene (0.3 mmol), base (0.6 mmol), solvent (0.1 M), 130 ꢀC for
18 h under N2. Calibrated GC-FID yields. 12.5 mol% of DPPF was
used. d Reaction without norbornene.
Results and discussion
b
c
At the outset of our investigation, we found that the reaction
between 2-bromobenzaldehyde hydrazone (2a) and 2-
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monophosphine ligands screened (entries 1–4), PCyPh2 withdrawing group such as –CF3 caused a drop in yield and 3f
provided the highest product yield (74%, entry 3). Either was isolated in 48% yield. Aryl iodides with sterically hindered
increasing or decreasing the electron richness of the phos- ortho-substituents such as phenyl or isopropyl groups under-
phorus donor led to a drop in product yield. Bulky cataCXium A went the transformation smoothly to afford the corresponding
and other biaryl phosphine ligands showed inferior activity in uorenes 3g and 3t in moderate-to-good yields. Heteroatom-
this comparison (entries 5–7). Bidentate phosphine such as containing and polyaromatic substrates were tolerated (3j–3l)
DPPF was not suitable for this reaction (entry 8). Cs2CO3 gave and it is worth to mention that polyaromatic hydrocarbons
a similar yield to that of K2CO3 and the later one was chosen for (PAHs) contribute important properties in light-emitting
further study because of its economical attractiveness (entry 3 devices and uorophores.30 We next turned our attention to
vs. 9). Gratifyingly, the product yield was further increased to the scope of aryl hydrazones 2. We were pleased that the
80% when DMF was employed as solvent (entry 3 vs. 11). Other transformations proceeded efficiently to give multi-substituted
solvents gave comparable performances to that of toluene uorenes 3l–3z with complete regioselectivity (up to 90%
(entries 12–13), except acetonitrile (entry 14). A control experi- yield). The structure of 3s was determined by single crystal X-ray
ment without norbornene was carried out and desired product analysis.31 Aryl hydrazones containing electron-donating and
was not observed (entry 15).
-withdrawing groups were applicable substrates (3m–3s). Poly-
Having identied an optimal reaction conditions, we then cyclic uoreno[1,3]dioxoles 3t and 3u were isolated in 80%
studied the reaction scope of our reaction. Aryl iodides with yield. The alkyl aryl ether (3w) and acetal group (3y) can be
different electron richness and steric bulkiness were rst tested readily transformed into phenol and aldehyde, respectively.
(Table 2, 3a–3l, 3q). Electron-rich and – neutral aryl iodides were Chloro group (3x) was compatible and provides access to further
converted to the desired products in 68–82% isolated yields (3a– functionalizations by palladium-catalyzed cross-couplings.32
3e, 3h–3i). However, substrates bearing an electron- Estrone-derived aryl iodide also reacted under the standard
Table 2 Substrate scopea
a
Reaction conditions: Pd(OAc)2 (10 mol%), PCyPh2 (25 mol%), aryl iodide (0.2 mmol), 2 (0.24 mmol), norbornene (0.3 mmol), K2CO3 (0.6 mmol),
DMF (0.1 M), 130 ꢀC for 18 h under N2. Isolated yields were reported.
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conditions to provide 3z in 75% isolated yield. Interestingly, 73% isolated yield, in which the yield only decreased slightly in
reaction of aryl iodides without ortho-substituents, or with comparison to entry 3a of Table 2.
small ortho-substituents such as uorine, gave norbornene-
A mechanistic proposal of our reaction is illustrated in
embedded heptagon compounds,33 in which it showed that Scheme 2. The cascade initiates with the oxidative addition of
the steric hindrance exerted by the ortho-substituents is critical 2-iodotoluene to Pd(0), followed by a migratory insertion of
for the extrusion of norbornene and thus the ve-membered NBE and palladation of the ortho-C–H bond to give the ANP
ring formation. Further study of this outcome is currently (aryl-norbornene palladacycle). Based on our previous works
underway in our laboratory.
and literature reports, it is reasonable to hypothesize the
To demonstrate the synthetic utility of our method in a wider formation of a Pd(IV) intermediate A from ANP.3,17 The hydra-
scope, we carried out a gram-scale synthesis and 1.26 g of u- zone chelates to the Pd(II) and assists with the oxidative addi-
orene 3a was successfully obtained under standard reaction tion of 2a by allowing the C–Br bond to sit near the Pd centre.
conditions (Scheme 1A). A diiodide substrate underwent the The reductive elimination of A generates the biarylpalladium(II)
transformation successfully to form a dialkyl ether-linked species B in a regioselective fashion and subsequent b-carbon
diuorene 4 in 51% yield (Scheme 1B). To circumvent the elimination of norbornene gives the key intermediate C. We
access of hydrazones in this tandem reaction, we sought to have observed a trace amount of intermediate E on GC-MS
adapt our system to a three-component reaction with in situ during the optimization studies, which suggests a possible
generation of the aryl hydrazone using 2-bromobenzaldehyde C–H activation on the hydrazone to form palladacycle D. The
and hydrazine (Scheme 1C). All commercially available mate- Wolff–Kishner reduction of E gives the nal product 3a.34
rials were employed and the desired product 3a was given in Alternatively, another possible pathway could be similar to the
cross-coupling of Umpolung aldehydes, which were very
recently reported by Li and co-workers.35 The deprotonation of
hydrazone forms a carbon nucleophile, which upon substitu-
tion with the bromide would yield palladacycle F. Reductive
elimination of F regenerates Pd(0) and affords intermediate G,
which undergoes denitrogenation to give 3a under a basic
condition. Although a deuterium labelling study was attempted
(Scheme S1†), the results were not conclusive due to the H/D
exchange nature of the C9-proton (pKa ¼ 22.6 in DMSO for
uorene) under basic conditions.36 The Wolff–Kishner reduc-
tion was also tested by subjecting hydrazone 5 under standard
reaction conditions in the absence of palladium catalyst
(Scheme 3A) and 50% yield of uorene 6 was obtained.
However, the addition of 10 mol% Pd catalyst to the system
increased the product yield of 6 to 73%, in which it is possible
that the reduction could be assisted by a palladium process.
Control experiments regarding the reaction pathway were
carried out (Scheme 3B). An N-tosyl hydrazone 7 was subjected
to the reaction system but no desired product was obtained,
indicating the absence of a carbene migratory insertion within
Scheme 1 Synthetic utilities of our reaction; (A) scalability of our
intermediate C. When the ketone-derived hydrazone 8 was
reaction; (B) reaction of a diiodide substrate; (C) in situ generation of
used, no corresponding product was detected, in which it
hydrazone in a three-component reaction.
Scheme 2 Mechanistic proposal.
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Ed., 2015, 54, 66; (c) H. Ito, K. Ozaki and K. Itami, Angew.
Chem., Int. Ed., 2017, 56, 11144; (d) J. Jeon, H. Ryu, C. Lee,
D. Cho, M.-H. Baik and S. Hong, J. Am. Chem. Soc., 2019,
141, 10048.
2 M. Catellani, F. Frignani and A. Rangoni, Angew. Chem., Int.
Ed., 1997, 36, 119.
3 Recent reviews on the Catellani reaction: (a) M. Catellani,
E. Motti and N. Della Ca', Acc. Chem. Res., 2008, 41, 1512;
(b) A. Martins, B. Mariampillai and M. Lautens, Top. Curr.
Chem., 2009, 292, 1; (c) R. Ferraccioli, Synthesis, 2013, 45,
581; (d) J. Ye and M. Lautens, Nat. Chem., 2015, 7, 863; (e)
N. Della Ca', M. Fontana, E. Motti and M. Catellani, Acc.
Chem. Res., 2016, 49, 1389; (f) J. Wang and G. Dong, Chem.
Rev., 2019, 119, 7478.
4 (a) M. Lautens and S. Piguel, Angew. Chem., Int. Ed., 2000, 39,
1045; (b) F. Faccini, E. Motti and M. Catellani, J. Am. Chem.
Soc., 2004, 126, 78.
5 E. Motti, M. Rossetti, G. Bocelli and M. Catellani, J.
Organomet. Chem., 2004, 689, 3741.
Scheme 3 (A) Wolff-Kishner reaction of 9-fluorenone hydrazone
under standard conditions as shown in Table 2, [Pd] ¼ 10 mol%
Pd(OAc)2 and 25 mol% PCyPh2; (B) mechanistic studies.
6 (a) M. Catellni, E. Motti and M. Minari, Chem. Commun.,
2000, 157; (b) C. Ye, H. Zhu and Z. Chen, J. Org. Chem.,
2014, 79, 8900.
reveals the importance of the C–H site for intramolecular C–H
activation by the Pd(II) centre.
7 (a) G. Maestri, N. Della Ca' and M. Catellani, Chem.
Commun., 2009, 4892; (b) W. C. Fu, B. Zheng, Q. Zhao,
W. T. K. Chan and F. Y. Kwong, Org. Lett., 2017, 19, 4335.
8 (a) P. Thansandote, M. Raemy, A. Rudolph and M. Lautens,
Org. Lett., 2007, 9, 5255; (b) D. A. Candito and M. Lautens,
Org. Lett., 2010, 12, 3312.
9 H. Shi, D. J. Babinski and T. Ritter, J. Am. Chem. Soc., 2015,
137, 3775.
10 (a) B. Mariampillai, D. Alberico, V. Bidau and M. Lautens, J.
Am. Chem. Soc., 2006, 127, 14436; (b) B. Luo, J.-M. Gao and
M. Lautens, Org. Lett., 2016, 18, 4166.
Conclusions
In summary, a denitrogenative palladium-catalyzed cascade has
been developed to allow for facile assembly of polysubstituted
uorenes. Hydrazone was utilized as a deciduous chelating
group to facilitate the Pd(II)/Pd(IV) oxidative addition in a Cat-
ellani cycle while it also served as a methylene synthon for the
uorene C-9 carbon. This modular synthesis exhibited complete
regioselectivity and provided uorenes with various substitu-
tion patterns in good-to-excellent product yields. In situ gener-
ation of hydrazones from aldehydes has also been illustrated in
a three-component cross-coupling reaction. We believe that the
reaction scope, as well as the use of a commercial catalyst and
easily available reactants, would render our method attractive
and versatile for synthetic applications in material science,
medicinal chemistry and organic chemistry.
11 C. Bressy, D. Alberico and M. Lautens, J. Am. Chem. Soc.,
2005, 127, 13148.
12 F. Sun, M. Li, C. He, B. Wang, B. Li, X. Sui and Z. Gu, J. Am.
Chem. Soc., 2016, 138, 7456.
13 Recent examples of Catellani-type reactions: (a) Z. Dong and
G. Dong, J. Am. Chem. Soc., 2013, 135, 18350; (b) P.-X. Zhou,
Y.-Y. Ye, C. Liu, L.-B. Zhao, J.-Y. Hou, D.-Q. Chen, Q. Tang,
A.-Q. Wang, J.-Y. Zhang, Q.-X. Huang, P.-F. Xu and
Y.-M. Liang, ACS Catal., 2015, 5, 4927; (c) Z. Dong, J. Wang,
Z. Ren and G. Dong, Angew. Chem., Int. Ed., 2015, 54,
12664; (d) X. Sui, L. Ding and Z. Gu, Chem. Commun., 2016,
52, 13999; (e) L. Fan, J. Liu, L. Bai, Y. Wang and X. Luan,
Angew. Chem., Int. Ed., 2017, 56, 14257; (f) G. Qian, M. Bai,
S. Gao, H. Chen, S. Zhou, H.-G. Cheng, W. Yan and
Q. Zhou, Angew. Chem., Int. Ed., 2018, 57, 10980; (g)
Z. Dong, G. Lu, J. Wang, P. Liu and G. Dong, J. Am. Chem.
Soc., 2018, 140, 8551; (h) L. Bai, J. Liu, W. Hu, K. Li,
Y. Wang and X. Luan, Angew. Chem., Int. Ed., 2018, 57,
5151; (i) Y. Yang, B. Zhou, X. Zhu, G. Deng, Y. Liang and
Y. Yang, Org. Lett., 2018, 20, 5402; (j) H. Zhou, W. Chen
and Z. Chen, Org. Lett., 2018, 20, 2590; (k) J. Wang, R. Li,
Z. Dong, P. Liu and G. Dong, Nat. Chem., 2018, 10, 866; (l)
A. Whyte, M. E. Olson and M. Lautens, Org. Lett., 2018, 20,
345; (m) J. Nan, Y. Yuan, L. Bai, J. Liu and X. Luan, Org.
Conflicts of interest
There are no conicts to declare.
Acknowledgements
We thank RGC of Hong Kong (GRF: 14307418) for nancial
support. CUHK direct grant (4053269, 4053322, 4442122) is
gratefully acknowledged. We thank Dr Pui Ying Choy (CUHK)
for helpful discussions. We also thank the nancial support
from Innovation and Technology Commission (HKSAR, China)
to the State Key Laboratory of Synthetic Chemistry.
Notes and references
1 (a) J. F. Hartwig, Chem. Soc. Rev., 2011, 40, 1992; (b)
Y. Segawa, T. Maekawa and K. Itami, Angew. Chem., Int.
This journal is © The Royal Society of Chemistry 2019
Chem. Sci.

View Article Online
Chemical Science
Edge Article
Lett., 2018, 20, 7731; (n) A. Casnati, M. Fontana, G. Coruzzi, 20 (a) J. Locklin, M. M. Ling, A. Sung, M. E. Roberts and Z. Bao,
B. M. Aresta, N. Corriero, R. Maggi, G. Maestri, E. Motti and
N. Della Ca', ChemCatChem, 2018, 10, 4346; (o) R. Li and
G. Dong, Angew. Chem., Int. Ed., 2018, 57, 1967; (p) W. Li,
W. Chen, B. Zhou, Y. Xu, G. Deng, Y. Liang and Y. Yang,
Org. Lett., 2019, 21, 2718; (q) P. Wang, S. Chen, Z. Zhou,
H.-G. Cheng and Q. Zhou, Org. Lett., 2019, 21, 3323; (r)
S. Chen, P. Wang, H.-G. Cheng, C. Yang and Q. Zhou,
Chem. Sci., 2019, 10, 8384–8389.
Adv. Mater., 2006, 18, 2989; (b) T. Qi, Y. Liu, W. Qiu,
H. Zhang, X. Gao, Y. Liu, K. Lu, C. Du, G. Yu and D. Zhu, J.
Mater. Chem., 2008, 18, 1131; (c) H. Chen, M. Hurhangee,
M. Nikolka, W. Zhang, M. Kirkus, M. Neophytou,
S. J. Cryer, D. Harkin, P. Hayoz, M. Abdi-Jalebi,
C. R. McNeill, H. Sirringhaus and I. McCulloch, Adv.
Mater., 2017, 29, 1702523.
21 (a) L. Wang, G.-W. Zhang, C.-J. Ou, L.-H. Xie, J.-Y. Lin,
Y.-Y. Liu and W. Huang, Org. Lett., 2014, 16, 1748; (b)
H. Zhong, C. Liu, Y. Wang, R. Wang and M. Hong, Chem.
Sci., 2016, 7, 2188; (c) L. Wang, B. Dong, R. Ge, F. Jiang
and J. Xu, ACS Appl. Mater. Interfaces, 2017, 9, 7108.
14 H.-G. Cheng, S. Chen, R. Chen and Q. Zhou, Angew. Chem.,
Int. Ed., 2019, 58, 5832.
15 For the use of directing groups in Catellani-type reactions:
(a) Y.-B. Zhao, B. Mariampillai, D. A. Candito, B. Laleu,
´
M. Li and M. Lautens, Angew. Chem., Int. Ed., 2009, 48, 22 (a) A. Donat-Bouillud, I. Levesque, Y. Tao, M. D'lorio,
´
1849; (b) P. Thansandote, E. Cheng, K.-O. Feldmann and
M. Lautens, J. Org. Chem., 2010, 75, 3495; (c) A. Martins,
D. A. Candito and M. Lautens, Org. Lett., 2010, 12, 5186;
S. Beaupre, P. Blondin, M. Ranger, J. Bouchard and
M. Leclerc, Chem. Mater., 2000, 12, 1931; (b) Q. Chen,
J.-X. Wang, Q. Wang, N. Bian, Z.-H. Li, C.-G. Yan and
B.-H. Han, Marcomolecules, 2011, 44, 7987; (c)
K. Nakabayashi, T. Imai, M.-C. Fu, S. Ando, T. Higashihara
and M. Ueda, Marcomolecules, 2016, 49, 5849.
´
(d) M. Larraue, G. Maestri, A. Beaume, E. Derat,
ˆ
C. Ollivier, L. Fensterbank, C. Courillon, E. Lacote,
M. Catellani and M. Malacria, Angew. Chem., Int. Ed., 2011,
50, 12253; (e) Z. Dong, J. Wang and G. Dong, J. Am. Chem. 23 (a) S. Yao, H.-Y. Ahn, X. Wang, J. Fu, E. W. V. Stryland,
Soc., 2015, 137, 5887; (f) J. Han, L. Zhang, Y. Zhu,
Y. Zheng, X. Chen, Z.-B. Huang, D.-Q. Shi and Y. Zhao,
Chem. Commun., 2016, 52, 6903; (g) D. Rasina, A. Kahler-
Quesada, S. Ziarelli, S. Warratz, H. Cao, S. Santoro,
L. Ackermann and L. Vaccaro, Green Chem., 2016, 18, 5025;
D. J. Hagan and K. D. Beleld, J. Org. Chem., 2010, 75,
3965; (b) K. D. Beleld, M. V. Bondar, A. Frazer,
A. R. Morales, O. D. Kachkovsky, I. A. Mikhailov,
A. E. Masunov and O. V. Przhonska, J. Phys. Chem. B, 2010,
114, 9313.
(h) P.-X. Ling, K. Chen and B.-F. Shi, Chem. Commun., 24 (a) G. Kumar, R. Agarwal and S. Swaminathan, Chem.
2017, 53, 2166.
Commun., 2012, 48, 2412; (b) Y. Shi and S. Gao,
Tetrahedron, 2016, 72, 1717.
16 Gooßen and co-workers rst introduced carboxyl group as
a deciduous directing group: (a) L. Huang, A. Biafora, 25 (a) K. Funchibe and T. Akiyama, J. Am. Chem. Soc., 2006, 128,
G. Zhang, V. Bragoni and L. J. Gooßen, Angew. Chem., Int.
Ed., 2016, 55, 6933; (b) A. Biafora and L. J. Gooßen, Synlett,
2017, 28, 1885. For selected examples on the use of
deciduous carboxylates in transition metal-catalyzed
reactions: (c) J. Tang, D. Hackenberger and L. J. Gooßen,
Angew. Chem., Int. Ed., 2016, 55, 11296; (d) A. Biafora,
B. A. Khan, J. Bahri, J. M. Hewer and L. J. Gooßen, Org.
1434; (b) N. Chernyak and V. Gevorgyan, J. Am. Chem. Soc.,
2008, 130, 5636; (c) D. J. Gorin, I. D. G. Watson and
F. D. Toste, J. Am. Chem. Soc., 2008, 130, 3736; (d) S. Zhu,
L. Wu and X. Huang, Org. Biomol. Chem., 2012, 10, 3696;
(e) Z. Liu, H. Tan, L. Wang, T. Fu, Y. Xia, Y. Zhang and
J. Wang, Angew. Chem., Int. Ed., 2015, 54, 3056; (f) Z.-J. Cai,
F.-H. Li, S.-Y. Wang and S.-J. Ji, Org. Lett., 2016, 18, 4810.
Lett., 2017, 19, 1232; (e) K. R. Bettadapur, V. Lanke and 26 (a) S. J. Hwang, H. J. Kim and S. Chang, Org. Lett., 2009, 11,
K. R. Prabhu, Chem. Commun., 2017, 53, 6251; (f)
R. N. P. Tulichala, M. Shankar and K. C. K Swamy, J. Org.
Chem., 2018, 83, 4375.
4588; (b) C.-C. Hsiao, Y.-K. Lin, C.-J. Liu, T.-C. Wu and
Y.-T. Wu, Adv. Synth. Catal., 2010, 352, 3267.
27 X. Zhang, L. Bu, Y. Qu, L. Wang, Y. Geng and F. Wang, J.
Mater. Chem., 2009, 19, 399.
17 (a) W. C. Fu, Z. Wang, W. T. K. Chan, Z. Lin and F. Y. Kwong,
Angew. Chem., Int. Ed., 2017, 56, 7166; (b) Q. Zhao, W. C. Fu 28 (a) C.-G. Dong and Q.-S. Hu, Org. Lett., 2006, 8, 5057; (b)
and F. Y. Kwong, Angew. Chem., Int. Ed., 2018, 57, 3381.
T.-P. Liu, C.-H. Xing and Q.-S. Hu, Angew. Chem., Int. Ed.,
2010, 49, 2909; (c) S. Xu, X. Shangguan, H. Li, Y. Zhang
and J. Wang, J. Org. Chem., 2015, 80, 7779; (d) G. Shi,
D. Chen, H. Jiang, Y. Zhang and Y. Zhang, Org. Lett., 2016,
18, 2958; (e) J. Song, W. Sun, Y. Li, F. Wei, C. Liu, Y. Qian
and S. Chen, Chem.–Asian J., 2016, 11, 211; (f) S. Xu,
R. Chen, Z. Fu, Q. Zhou, Y. Zhang and J. Wang, ACS Catal.,
2017, 7, 1993.
´
´
´
18 (a) A. Ros, R. Lopez-Rodrıguez, B. Estepa, E. Alvarez,
´
R. Fernandez and J. M. Lassaletta, J. Am. Chem. Soc., 2012,
134, 4573; (b) Z. Huang, C. Wang and G. Dong, Angew.
Chem., Int. Ed., 2016, 55, 5299; (c) P. Xu, G. Wang, Z. Wu,
S. Li and C. Zhu, Chem. Sci., 2017, 8, 1303.
19 (a) M. P. Aldred, A. J. Eastwood, S. M. Kelly, P. Vlachos,
A. E. A. Contoret, S. R. Farrar, B. Mansoor, M. O'Neill and
´
W. C. Tsoi, Chem. Mater., 2004, 16, 4928; (b) J. U. Wallace 29 (a) B. Liegault, D. Lee, M. P. Huestis, D. R. Stuart and
and S. H. Chen, in Polyuorenes Advances in Polymer
Science, ed. U. Scherf and D. Neher, Springer, Berlin,
Heidelberg, 2008, pp. 145–186; (c) R. Abbel,
A. P. H. J. Schenning and E. W. Meijer, J. Polym. Sci., Part
A: Polym. Chem., 2009, 47, 4215.
K. Fagnou, J. Org. Chem., 2008, 73, 5022; (b) R. Che, Z. Wu,
Z. Li, H. Xiang and X. Zhou, Chem.–Eur. J., 2014, 20, 7258;
(c) D.-D. Guo, B. Li, D.-Y. Wang, Y.-R. Gao, S.-H. Guo,
G.-F. Pan and Y.-Q. Wang, Org. Lett., 2017, 19, 798.
Chem. Sci.
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30 (a) Z. Sun, Q. Ye, C. Chi and J. Wu, Chem. Soc. Rev., 2012, 41, 34 (a) N. Kishner, J. Russ. Phys.-Chem. Soc., 1911, 43, 582; (b)
7857; (b) M. Li, C. An, T. Marszalek, X. Guo, Y.-Z. Long,
L. Wolff, Justus Liebigs Ann. Chem., 1912, 394, 86; Recent
literature: (c) M. E. Furrow and A. G. Myers, J. Am. Chem.
Soc., 2004, 126, 5436; (d) X.-J. Dai and C.-J. Li, J. Am. Chem.
Soc., 2016, 138, 5433.
¨
H. Yin, C. Gu, M. Baumgarten, W. Pisula and K. Mullen,
Chem. Mater., 2015, 27, 2218.
31 The X-ray crystallographic data for 3s (CCDC 1833356).
32 (a) T. Jia, A. Bellomo, K. E. Baina, S. D. Dreher and 35 (a) D. Zhu, L. Lv, C.-C. Li, S. Ung, J. Gao and C.-J. Li, Angew.
P. J. Walsh, J. Am. Chem. Soc., 2013, 135, 3740; (b) J. Zhang,
A. Bellomo, N. Trongsiriwat, T. Jia, P. J. Carroll,
S. D. Dreher, M. T. Tudge, H. Yin, J. R. Robinson,
E. J. Schelter and P. J. Walsh, J. Am. Chem. Soc., 2014, 136,
6276.
Chem., Int. Ed., 2018, 57, 16520; (b) L. Lv, D. Zhu, J. Tang,
Z. Qiu, C.-C. Li, J. Gao and C.-J. Li, ACS Catal., 2018, 8,
4622; (c) D. Zhu, L. Lv, Z. Qiu and C.-J. Li, J. Org. Chem.,
2019, 84, 6312.
36 F. G. Bordwell, Acc. Chem. Res., 1988, 21, 456.
33 The general structure is 4b,6,7,8,8a,9-hexahydro-5H-5,8-
methanotribenzo[a,c,e][7]annulene.
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