Copper-Catalyzed Chemo- and Diastereoselective 1,3-Dipolar Cycloaddition of Carbonyl Ylide and Aldehyde-Tethered-Cyclohexadienone to Access Polycyclic Systems

Article abstract of DOI:10.1002/adsc.202100648

A copper-catalyzed tandem intermolecular ylide formation/intramolecular cycloaddition of diazo compounds and aldehyde-tethered-cyclohexadienones was reported, chemo- and diastereoselectively providing oxapolycyclic frameworks in moderate to excellent yields under mild conditions. This reaction creates two C?C bonds and one C?O bond with five stereocentres including two all-carbon quaternary centres. Moreover, the late-stage diversification of products can be realized via chemoselective substitutions. (Figure presented.).

Full text of DOI:10.1002/adsc.202100648

COMMUNICATIONS
doi.org/10.1002/adsc.202100648
Copper-Catalyzed Chemo- and Diastereoselective 1,3-Dipolar
Cycloaddition of Carbonyl Ylide and Aldehyde-Tethered-
Cyclohexadienone to Access Polycyclic Systems
Shiyong Peng,a,* Hong Zhang,a Yuqi Zhu,a Ting Zhou,a Jieyin He,a Nuan Chen,a
Ming Lang,a Hongguang Li,a and Jian Wanga, b,*
a
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, People’s Republic of China
E-mail: psy880124@mail.nankai.edu.cn
School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorous Chemistry & Chemical Biology (Ministry of
b
Education), Tsinghua University, Beijing, 100084, People’s Republic of China
E-mail: wangjian2012@tsinghua.edu.cn
Manuscript received: May 27, 2021; Revised manuscript received: July 24, 2021;
Version of record online: ■■■, ■■■■
Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.202100648
construction of functionalized oxygen heterocycles
Abstract: A copper-catalyzed tandem intermolecu-
(Scheme 1a).[3] Nevertheless, it has been relatively
lar ylide formation/intramolecular cycloaddition of
restricted in terms of selectivity and substrate scope. In
diazo compounds and aldehyde-tethered-cyclohexa-
the last decades, great attentions have been paid to the
dienones was reported, chemo- and diastereoselec-
intramolecular carbonyl ylide cycloaddition, including
tively providing oxapolycyclic frameworks in mod-
intramolecular ylide formation/intermolecular cyclo-
erate to excellent yields under mild conditions. This
addition (Scheme 1b)[4] and intramolecular ylide for-
reaction creates two CÀ C bonds and one CÀ O bond
with five stereocentres including two all-carbon
quaternary centres. Moreover, the late-stage diversi-
fication of products can be realized via chemo-
selective substitutions.
mation/intramolecular cycloaddition (Scheme 1c),[5] for
the synthesis of complex targets.
In contrast, analogous two component reactions
involving tandem intermolecular ylide formation/intra-
molecular cycloaddition has been relatively limited
(Scheme 1d). In 2001, Johnson and co-workers de-
scribed an interesting example of rhodium-catalyzed
intermolecular ylide for-mation/intramolecular cyclo-
addition of diazosulphone and alkynyl/alkenyl alde-
Keywords: copper catalysis; 1,3-dipolar cycloaddi-
tion; carbonyl ylide; polycyclic structure
hydes,
affording
substituted
furans
or
tetrahydrofurans.[6] Recently, Muthusamy et al. devel-
Transition-metal-catalyzed inter- or intramolecular re- oped a copper-catalyzed tandem reaction of diazoa-
actions of diazo compounds and Lewis bases are mides and O-propargyl salicylaldehydes for the syn-
powerful tools to generate ylides, which are usually thesis
of
spiro-indolofurobenzopyrans
via
highly reactive species and readily undergo further intermolecular ylide formation/intramolecular cyclo-
tandem reactions for the creation of new chemical addition process;[7] in comparison, Bakthadoss et al.
entities.[1] Particularly, carbonyl ylides formed by the reported a similar rhodium-catalyzed protocol of diazo
transition-metal-catalyzed reaction of diazo compounds dicarbonyl compounds and O-allylated salicylalde-
and carbon-oxygen double bonds are reactive inter- hydes for the construction of tricyclic chromeno/
mediates and could undergo diverse transformations, quinolino furan frameworks.[8] Despite these consider-
among which the 1,3-dipolar cy-cloaddition of such able advances, there was still not a general method for
carbonyl ylides has been studied extensively and used the two-component intermolecular ylide formation/
for the construction of complex oxapolycyclic systems intramolecular cycloaddition with broad scope and
containing embedded di- or tetrahydrofuran rings.[2]
The three-component intermolecular carbonyl ylide
control over chemo- and diastereoselectivity.
On the other hand, these 1,3-dipolar cycloaddition
cycloaddition involving diazo compounds, aldehydes, of carbonyl ylide were commonly catalyzed by
and dipolarophiles is an effective method for the rhodium complexes.[1,2] Inspired by the former reports
Adv. Synth. Catal. 2021, 363, 1–7
1
© 2021 Wiley-VCH GmbH
��
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
lower yield (entry 11), and the reaction did not happen
under low temperature (entry 12). Significantly, the
yield of 3aa was reduced to 27% in the absence of
prestirring of the aldehyde with the copper complex
(entry 13), and no product was isolated without slow
addition of the diazo substrate (entry 14). Control
experiment without copper catalyst yielded no product
(entry 15). It is noteworthy that the carboxylic acid
ligands of rhodium catalysts have obvious effect on the
stereochemistry, which demonstrates that a Rh-ligated
ylide intermediate is probably formed; while different
copper catalysts with or without chiral ligands have no
influence on the stereochemistry indicating that the
reaction might take place via a metal-free ylide under
copper catalysis (Supporting Information). It is pro-
posed that the steric effect for the free carbonyl ylide
resulted better diastereoselectivity, while the steric
effect and ligated-metal for the metal-ligated carbonyl
ylide would make the reaction complex with poor
diastereocontrol.
With the optimal reaction conditions in hand,[12] we
next set out to investigate the scope of diazo
compounds (Table 2). Varying the ester group of diazo
compounds to bulky ethyl or benzyl substitutent gave
lower yields (3aa–ca). Then, the reaction of aldehyde-
tethered-cyclohexadienone 2a with different substi-
tuted aryl diazoacetates bearing electron-donating or
Scheme 1. Previous Reports and Our Strategy.
and in continuation with our interest in catalytic electron-withdrawing substituents at the para- and
copper-carbene transformations for developing novel meta-position of the aryl moiety all proceeded
methodologies on polycyclic skeleton synthesis,[9] smoothly to furnish the desired products (3da–oa),
herein, we report a novel copper-catalyzed tandem while the yield sharply decreased for ortho-substituted
intermolecular ylide formation/intramolecular 1,3-di- diazo compounds, indicating that the steric effect is
polar cycloaddition of diazo compounds and aldehyde- more significant than the electronic factor for this
tethered-cyclohexadienones to access various oxapoly- reaction (3pa–qa). Additionally, different di-substi-
cyclic systems with excellent chemo- and diastereose- tuted phenyl diazoacetates and bulky naphthyl diazo-
lectivities and moderate to excellent yields under mild acetate were also well tolerated for the reaction (3ra–
conditions (Scheme 1e).
ua). When 3-diazo-oxindole substrate was applied to
We first utilized phenyl diazoacetate 1a and the reaction, an interesting spiro-oxindole fused hex-
aldehyde-tethered-cyclohexadienone 2a as model sub- acyclic framework was obtained in one step (3va–wa),
strates to optimize the reaction conditions (Table 1). which is attractive for medicinal chemistry.[13] More-
When the reaction was performed in methylene over, because the structure of diazo compound has a
dichloride (CH2Cl2) at room temperature with large impact on the reaction outcome,[14] other types of
Rh2(OAc)4 as the catalyst, the desired product 3aa was diazo compounds were further tested for this reaction.
obtained in 36% yield with moderate diastereoselectiv- Gratifyingly, dimethyl 2-diazomalonate was suitable
ity (entry 1).[10] The reaction was highly sensitive to for this reaction, affording the desired product 3xa in
moisture, and no desired product was detected without 47% yield. However, no target product 3ya was
4 Å MS (entry 2). Inspired by Muthusamy’s report,[7] detected from the reaction mixture when (1-diazoethyl)
copper catalysts were extensively investigated, and benzene was utilized. The structure and relative stereo-
gratifyingly, Cu(COD)(hfac) has been proven to be the chemistry of 3aa were unambiguously confirmed by
best catalyst, affording the desired product 3aa in 34% X-ray diffraction analysis.[15]
yield as single diastereomer (entries 3–5). Next, differ-
Next, various substituted aldehyde-tethered-cyclo-
ent solvents were screened. (Trifluoromethyl)benzene hexadienone substrates were subjected to the optimized
(PhCF3) was the best choice, and the alternative reaction conditions and generally showed somehow
aromatic solvents including toluene, xylenes, and lower efficiency (Table 3). The influence of the R
chlorobenzene (PhCl) gave moderate yields,[11] whereas substituent was first investigated. Changing the R
the other solvents were not suitable for the reaction group of cyclohexadienones from methyl to ethyl or
(entries 6–10). Moreover, high temperature led to a acetyl group had adverse effect on the reaction,
Adv. Synth. Catal. 2021, 363, 1–7
2
© 2021 Wiley-VCH GmbH
��
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
Table 1. Optimization of Reaction Conditions.[a]
Entry
Catalyst
Solvent
Yield
(%)[b]
dr[c]
1
Rh2(OAc)4
Rh2(OAc)4
CuOTf
Cu(COD)(hfac)
Cu(hfac)2
Cu(COD)(hfac)
Cu(COD)(hfac)
Cu(COD)(hfac)
Cu(COD)(hfac)
Cu(COD)(hfac)
Cu(COD)(hfac)
Cu(COD)(hfac)
Cu(COD)(hfac)
Cu(COD)(hfac)
–
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
dioxane
toluene
xylenes
PhCl
PhCF3
PhCF3
PhCF3
PhCF3
PhCF3
PhCF3
36
–
8
4:1
–
2[d]
3
> 20:1
> 20:1
> 20:1
–
> 20:1
> 20:1
> 20:1
> 20:1
> 20:1
–
4
5
6
7
8
9
10
11[e]
12[f]
13[g]
14[h]
15
34
15
–
53
48
64
71
33
–
27
–
–
> 20:1
–
–
[a] Reaction conditions: a mixture of 2a (0.3 mmol), catalyst ([Rh] 5 mol%, [Cu] 10 mol%) and 4 Å MS (300 mg) in solvent
(1.0 mL) was prestirred for 2 h; then, a solution of 1a (0.6 mmol) in solvent (2.0 mL) was injected over 2 h via an automatic
syringe pump; the reaction was continued for 16 h at rt.
[b] Isolated yields.
1
1
[c] Determined by H NMR. When no signals of minor diastereomers were detected in the crude and pure H NMR, the
diastereoselectivity is quoted as>20:1.
[d] Without 4 Å MS.
[e]
°
At 80 C.
[f]
°
At 0 C.
[g] Without prestirring.
[h] 1a (0.6 mmol) in PhCF3 (2.0 mL) was added in one portion.
providing the corresponding products 3ab and 3ac in
42% and 40% yields, respectively. Then, the substitu-
tion pattern on the aryl moiety was examined.
Substrates bearing electron-donating or electron-with-
drawing substituents on the 3-, 4- or 5-position of the
aryl moiety all proceeded smoothly to afford the
corresponding products in moderate to excellent yields
(3ad–al); the 2-substituted product was not obtained
due to the unavailability of the corresponding cyclo-
hexadienone substrate. To our delight, when the asym-
metrical cyclohexadienone with a 3’-chloro group was
employed, the expected product 3am was obtained
regioselectively in 49% yield. Unfortunately, the furan-
derived cyclohexadienone was not applicable for the
reaction (3an).
To further understand the tandem intermolecular
ylide formation/intramolecular cycloaddition process,
several control experiments were conducted
(Scheme 2). When substrate 2o was applied to the
reaction, no desired product 3ao was detected, which
Scheme 2. Control Experiments.
Adv. Synth. Catal. 2021, 363, 1–7
3
© 2021 Wiley-VCH GmbH
��
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
Table 2. Scope of Diazo Substrates.[a,b]
Table 3. Scope of Aldehyde-Tethered-Cyclohexadienone Sub-
strates.[a,b]
[a] Reaction conditions: a mixture of 2 (0.3 mmol), Cu-
(COD)(hfac) (10 mol%) and 4 Å MS (300 mg) in PhCF3
(1.0 mL) was prestirred for 2 h; then, a solution of 1a
(0.6 mmol) in PhCF3 (2.0 mL) was injected over 2 h via an
automatic syringe pump; the reaction was continued for 16 h
at rt.
[b] Isolated yields.
cyclohexadienone, and benzaldehyde afforded no prod-
uct 3ap or related isomers (Scheme 2b). Based on the
literature reports,[7,16] we tried to open the epoxide ring
by heating to generate the carbonyl ylide, which in
turn will undergo [3+2] cycloaddition. Accordingly,
the epoxide 4aa was tested under elevated temper-
ature, however, no desired product 3aa was isolated
(Scheme 2c).
[a] Reaction conditions: a mixture of 2a (0.3 mmol), Cu-
(COD)(hfac) (10 mol%) and 4 Å MS (300 mg) in PhCF3
(1.0 mL) was prestirred for 2 h; then, a solution of 1
(0.6 mmol) in PhCF3 (2.0 mL) was injected over 2 h via an
automatic syringe pump; the reaction was continued for 16 h
at rt.
[b] Isolated yields.
Based on the above results and related reports,[17]
a
plausible mechanism was illustrated in Scheme 3. The
indicates that the aromatic linker is essential for this catalytic cycle starts with the formation of the copper-
reaction and may stabilize the carbonyl ylide inter- carbene I by the reaction of phenyl diazoacetate 1a
mediate (Scheme 2a). Then, the three-component inter- with copper catalyst. Interaction of the aldehyde group
molecular cycloaddition involving diazo compound, in cyclohexadienone 2a with the copper-carbene I
Adv. Synth. Catal. 2021, 363, 1–7
4
© 2021 Wiley-VCH GmbH
��
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
economical alternative to diverse complex structures
attractive for medicinal chemistry. Further studies
based on this chemistry is in progress in our
laboratory.
Experimental Section
General Procedure for the Preparation of Com-
pounds 3
Scheme 3. Proposed Reaction Mechanism.
A
solution of aldehyde-tethered-cyclohexadienones
2
(0.3 mmol, 1.0 equiv.), 4 Å MS (300 mg) and Cu(COD)(hfac)
(10 mol%) in PhCF3 (1.0 mL) was stirred at rt for 2 h. Then a
solution of diazo compounds 1 (0.6 mmol, 2.0 equiv.) in PhCF3
(2.0 mL) was injected via an automatic syringe pump over 2 h
at rt and continued for another 16 h. The resulting mixture was
filtered via a short pad of celite and washed with EtOAc. The
combined organic phase was concentrated under reduced
pressure and the residue was purified by flash chromatography
(silica gel, EtOAc/hexanes as eluent) to afford the correspond-
ing products 3.
produces the free carbonyl ylide II and its polar-
reversed resonance structure III with the release of
copper catalyst. Here, the necessity of the aromatic
linker could be explained by the stabilization of the
ylide intermediate III. Then, the carbonyl ylide III
undergoes Huisgen intramolecular 1,3-dipolar cyclo-
addition with the alkene dipolarophile would give the
desired product 3aa. The carbonyl ylides II/III
proceed via competitive electrocyclization to yield the
epoxide side product 4aa.
Acknowledgements
The versatility of this copper-catalyzed protocol can
be further exploited in chemoselective substitutions
(Scheme 4). For examples, treatment of 3aa with
The authors are grateful for the financial support from the
Natural Science Foundation of Guangdong Province
(2018A030310680), the Research Foundation of Department of
Education of Guangdong Province (2018KTSCX236,
2020KTSCX154, 2020KCXTD036), the Science Foundation for
Young Teachers of Wuyi University (2019td09), and the College
Students Innovation and Entrepreneurship Training Program of
Wuyi University (2020CX08).
°
EtMgBr in THF at 0 C followed by quenching with
water furnished the ketone product 5 in 60% yield;[15]
the site-selective iron-catalyzed Friedel-Crafts aryla-
tion of 3ba with trimethoxybenzene proceeded
smoothly to offer product 6 in 83% yield.[18]
In summary, we have developed a copper-catalyzed
tandem intermolecular ylide formation/intramolecular
cycloaddition of diazo compounds and aldehyde-
tethered-cyclohexadienones to afford polycyclic struc-
tures in moderate to excellent yields under mild
conditions. This reaction creates two CÀ C bonds and
one CÀ O bond with five stereocentres including two
all-carbon quaternary centers with high chemo- and
diastereoselectivities. It is believed that the continued
and renewed investigation on the copper-catalyzed 1,3-
dipolar cycloaddition of carbonyl ylide will provide an
References
[1] For typical reviews, see: a) A. Padwa, S. F. Hornbuckle,
Chem. Rev. 1991, 91, 263–309; b) T. Ye, M. A.
McKervey, Chem. Rev. 1994, 94, 1091–1160; c) A. Ford,
H. Miel, A. Ring, C. N. Slattery, A. R. Maguire, M. A.
McKervey, Chem. Rev. 2015, 115, 9981–10080.
[2] For typical reviews, see: a) A. Padwa, M. D. Weingarten,
Chem. Rev. 1996, 96, 223–270; b) D. M. Hodgson,
F. Y. T. M. Pierard, P. A. Stupple, Chem. Soc. Rev. 2001,
30, 50–61; c) G. Mehta, S. Muthusamy, Tetrahedron
2002, 58, 9477–9504; d) A. Padwa, Chem. Soc. Rev.
2009, 38, 3072–3081; e) S. France, L. H. Phun, Curr.
Org. Synth. 2010, 7, 332–347.
[3] For typical reports, see: a) M. P. Doyle, D. C. Forbes,
M. N. Protopopova, S. A. Stanley, M. M. Vasbinder,
K. R. Xavier, J. Org. Chem. 1997, 62, 7210–7215; b) S.
Torssell, M. Kienle, P. Somfai, Angew. Chem. Int. Ed.
2005, 44, 3096–3099; Angew. Chem. 2005, 117, 3156–
3159; c) A. DeAngelis, M. T. Taylor, J. M. Fox, J. Am.
Chem. Soc. 2009, 131, 1101–1105; d) X. Xu, X. Guo, X.
Han, L. Yang, W.-H. Hu, Org. Chem. Front. 2014, 1,
181–185; e) T. Rajasekaran, B. Sridhar, B. V. Subba R-
eddy, Tetrahedron 2016, 72, 2102–2108; f) Y. Toda, W.
Kaku, M. Tsuruoka, S. Shinogaki, T. Abe, H. Kamiya, A.
Scheme 4. Transformation of Products.
Adv. Synth. Catal. 2021, 363, 1–7
5
© 2021 Wiley-VCH GmbH
��
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
Kikuchi, K. Itoh, H. Suga, Org. Lett. 2018, 20, 2659–
2662.
d) N. Chen, M. He, T. Zhou, Y. Zhu, H. Zhang, S. Peng,
Synthesis 2021, 53, 611–622.
[4] For typical reports, see: a) H. Suga, H. Ishida, T. Ibata, [10] Although the diastereomers are not separable, the dr ratio
Tetrahedron Lett. 1998, 39, 3165–3166; b) S. Kitagaki,
M. Anada, O. Kataoka, K. Matsuno, C. Umeda, N.
could be easily determined via 1H NMR. Please see
Supporting Information for details.
Watanabe, S.-i. Hashimoto, J. Am. Chem. Soc. 1999, 121, [11] In general, aromatic solvents are suitable for this
1417–1418; c) A. Padwa, J. P. Snyder, E. A. Curtis,
S. M. Sheehan, K. J. Worsencroft, C. O. Kappe, J. Am.
reaction. It is proposed that the higher polarity of PhCF3
would contribute to the better result.
Chem. Soc. 2000, 122, 8155–8167; d) H. Suga, K. Inoue, [12] After extensive optimizations, the main epoxide side
S. Inoue, A. Kakehi, J. Am. Chem. Soc. 2002, 124,
14836–14837; e) D. M. Hodgson, T. Brückl, R. Glen,
A. H. Labande, D. A. Selden, A. G. Dossetter, A. J.
Redgrave, Proc. Natl. Acad. Sci. U.S.A. 2004, 101,
5450–5454.
reaction could not completely suppressed regardless of
the catalytic system, which is a major reason for the
general low efficiency of this reaction. However, pure
4aa is difficult to isolate and could only be obtained by
repeated preparative thin layer chromatography. Thus,
the amount of 4aa and others is not reported. By control
experiments shown in Scheme 2c, 4aa is quite stable to
the copper catalyst and the reaction conditions.
[5] For typical reports, see: a) D. M. Hodgson, P. A. Stupple,
C. Johnstone, Tetrahedron Lett. 1997, 38, 6471–6472;
b) M. A. Brodney, A. Padwa, J. Org. Chem. 1999, 64,
556–565; c) J. M. Mejía-Oneto, A. Padwa, Org. Lett. [13] G. S. Singh, Z. Y. Desta, Chem. Rev. 2012, 112, 6104–
2004, 6, 3241–3244; d) D. M. Hodgson, D. Angrish, 6155.
A. H. Labande, Chem. Commun. 2006, 627–628; e) X. [14] M. P. Doyle, M. A. McKervey, T. Ye, Modern Catalytic
Zhang, R. Y. Y. Ko, S. Li, R. Miao, P. Chiu, Synlett 2006,
2006, 1197–1200; f) D. B. England, J. M. Eagan, G.
Methods for Organic Synthesis with Diazo Compounds;
John Wiley & Sons: New York, 1998.
Merey, O. Anac, A. Padwa, Tetrahedron 2008, 64, 988– [15] CCDC 2072373 (3aa) and CCDC 2073472 (5) contain
1001; g) B. Shi, S. Merten, D. K. Y. Wong, J. C. K. Chu,
L. L. Liu, S. K. Lam, A. Jäger, W.-T. Wong, P. Chiu, P.
Metz, Adv. Synth. Catal. 2009, 351, 3128–3132.
[6] T. Johnson, D. R. Cheshire, M. J. Stocks, V. T. Thurston,
Synlett 2001, 646–648.
[7] S. Muthusamy, A. Prabu, E. Suresh, Org. Biomol. Chem.
2019, 17, 8088–8093.
[8] M. Bakthadoss, V. Agarwal, J. Org. Chem. 2020, 85,
15221–15231.
the crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_re-
quest/cif.
[16] a) R. Huisgen, Angew. Chem. Int. Ed. 1977, 16, 572–
585; Angew. Chem. 1977, 89, 589–602; b) W. Eberbach,
J. Brokatzky, H. Fritz, Angew. Chem. Int. Ed. 1980, 19,
47–48; Angew. Chem. 1980, 92, 48–49.
[17] a) B. V. S. Reddy, G. Karthik, T. Rajasekaran, B. Sridhar,
Eur. J. Org. Chem. 2015, 2038–2041; b) L. Qiu, D.
Wang, Y. Lei, L. Gao, S. Liu, J. Li, W. Hu, Eur. J. Org.
Chem. 2016, 2671–2680.
[9] a) M. He, N. Chen, T. Zhou, Q. Li, H. Li, M. Lang, J.
Wang, S. Peng, Org. Lett. 2019, 21, 9559–9563; b) M.
He, N. Chen, L. Liu, Y. Zhu, Q. Li, H. Li, M. Lang, J.
Wang, S. Peng, J. Org. Chem. 2020, 85, 4418–4429; [18] Y. Sawama, M. Masuda, R. Nakatani, H. Yokoyama, Y.
c) N. Chen, T. Zhou, H. Zhang, Y. Zhu, M. Lang, J.
Wang, S. Peng, J. Org. Chem. 2021, 86, 4714–4732;
Monguchi, T. Dohi, Y. Kita, H. Sajikia, Adv. Synth.
Catal. 2016, 358, 3683–3687.
Adv. Synth. Catal. 2021, 363, 1–7
6
© 2021 Wiley-VCH GmbH
��
These are not the final page numbers!

COMMUNICATIONS
Copper-Catalyzed Chemo- and Diastereoselective 1,3-
Dipolar Cycloaddition of Carbonyl Ylide and Aldehyde-
Tethered-Cyclohexadienone to Access Polycyclic Systems
Adv. Synth. Catal. 2021, 363, 1–7
S. Peng*, H. Zhang, Y. Zhu, T. Zhou, J. He, N. Chen, M.
Lang, H. Li, J. Wang*