Palladium-Catalyzed Asymmetric [8+2] Dipolar Cycloadditions of Vinyl Carbamates and Photogenerated Ketenes

Article abstract of DOI:10.1002/anie.202005313

Higher-order cycloadditions, particularly [8+2] cycloadditions, are a straightforward and efficient strategy for constructing significant medium-sized architectures. Typically, configuration-restrained conjugated systems are utilized as 8π-components for

Full text of DOI:10.1002/anie.202005313

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Accepted Article
Title: Palladium-Catalyzed Asymmetric [8+2] Dipolar Cycloadditions of
Vinyl Carbamates and Photogenerated Ketenes
Authors: Liang-Qiu Lu, Qun-Liang Zhang, Qin Xiong, Miao-Miao Li,
Wei Xiong, Bing Shi, Yu Lan, and Wen-Jing Xiao
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10.1002/anie.202005313
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Palladium-Catalyzed Asymmetric [8+2] Dipolar Cycloadditions of
Vinyl Carbamates and Photogenerated Ketenes
Qun-Liang Zhang[a], Qin Xiong[b], Miao-Miao Li[a], Wei Xiong[a], Bing Shi[a], Yu Lan*[b,c], Liang-Qiu Lu*[a,d], and
Wen-Jing Xiao[a]
Abstract: Higher-order cycloadditions, particularly [8+2] cycloaddi-
tions, are a straightforward and efficient strategy for constructing
significant medium-sized architectures. Typically, configuration-
restrained conjugated systems are utilized as 8π-components for
higher-order concerted cycloadditions. However, for this reason, 10-
membered monocyclic skeletons have never been constructed via
the catalytic asymmetric [8+2] cycloaddition with high peri- and
stereoselectivity. Here, beyond traditional concerted processes, we
accomplish an enantioselective [8+2] dipolar cycloaddition via the
merger of visible light activation and asymmetric palladium catalysis.
This protocol provides a new route to 10-membered monocyclic
architectures bearing chiral quaternary stereocenters with high
chemo-, peri-, and enantioselectivity. The success of this strategy
relied on the facile in-situ generation of Pd-containing 1,8-dipoles
and their enantioselective trapping by ketene dipolarophiles, which
were formed in situ via a photo-Wolff rearrangement.
heptafulvenes with 2-cycloalkenones, affording polycyclic cy-
cloadducts in moderate yields and high stereoselectivities (Fig-
ure 1B). Despite these great advances, the development of new
concepts and catalysis systems beyond concerted cycloaddi-
tions and the construction of 10-membered monocyclic skele-
tons are still highly desirable.[1b]
Over the past six decades, the importance of higher-order
cycloadditions for the construction of medium-sized heterocyclic
skeletons has been demonstrated.[1] In this context, since the
first work from Doering and Wiley in 1960,[2] a variety of [8+2]
cycloadditions have been developed.[3] These transformations
usually require configuration-restrained, conjugated 8π-
components[4-6] to reduce the reaction complexity and entropic
barriers, i.e., to disfavour intramolecular cyclizations and facili-
tate the periselectivity. Thus, only polycyclic products containing
10-membered units can be obtained with the previous strategies.
In addition to chemo- and periselectivity, good enantiocontrol
remains a formidable challenge in asymmetric [8+2] cycloaddi-
tions. Recently, impressive breakthroughs were achieved by
using reactants bearing cycloheptatriene units.[4,7] For example,
in 2013, the group of Feng[4a] reported the first Lewis acid-
catalyzed enantioselective [8+2] cycloaddition of azaheptaful-
venes with alkylidene malonates, producing cycloheptatriene-
fused pyrroles in high yields and enantioselectivities (Figure 1A).
In 2017, Jørgensen and coworkers[4b] disclosed the first organo-
catalytic asymmetric [8+2] cycloaddition of electron-deficient
Figure 1. Design plan of catalytic asymmetric [8+2] dipolar cycloadditions.
Based on the pioneering works of Trost[8a] and Tsuji,[8b] di-
polar cycloadditions built upon Pd-catalyzed allylic alkylations
have been established as a powerful tool for carbo- and hetero-
cycle synthesis.[9] In this field, vinyl carbamates were always
utilized as versatile precursors for Pd-containing reactive dipoles
through the oxidative addition of a Pd(0) catalyst followed by the
release of carbon dioxide (CO2) from the resulting zwitterionic
intermediate.[10] Based on the continued interest in transition-
metal-catalyzed dipolar cycloaddition (TMCDC) reactions,[10d,11]
we wondered whether the CO2 unit could be retained,[12] thus
providing a promising opportunity for higher-order dipolar cy-
cloadditions. As proposed in Figure 1C, vinyl carbamates 1 were
in situ converted to Pd-containing 1,8-dipoles I by reacting with
suitable Pd(0) catalysts, and reactive ketene dipolarophiles II[13]
were generated through photo-Wolff rearrangements upon
exposure of α-diazoketone 2 to visible light.[11c,11e,14] Then, the
nucleophilic addition of the carbonate anions to the ketenes and
the subsequent intramolecular allylation of the enolate interme-
diates would result in desired 10-membered monocyclic product
3. Though reasonable in principle, there are three selectivity
issues making the proposed pathway challenging: 1) the intra-
molecular cyclization of intermediate I or its decarboxylative
[a]
Q.-L. Zhang, M.-M. Li, W. Xiong, B. Shi, Prof. L.-Q. Lu, Prof. W.-J.
Xiao
CCNU-uOttawa Joint Research Centre, Key Laboratory of Pesticide
& Chemical Biology, Ministry of Education, College of Chemistry,
Central China Normal University, 152 Luoyu Road, Wuhan, Hubei
430079, China
E-mail: luliangqiu@mail.ccnu.edu.cn
[b]
Q. Xiong, Prof. Y. Lan
School of Chemistry and Chemical Engineering, Chongqing Univer-
sity, Chongqing 400030, China
Email: lanyu@cqu.edu.cn
[b]
[d]
Prof. Y. Lan
College of Chemistry, and Institute of Green Catalysis, Zhengzhou
University, Zhengzhou, Henan, 450001, China
Prof. L.-Q. Lu
State Key Laboratory for Oxo Synthesis and Selective Oxidation,
Lanzhou Institute of Chemical Physics (LICP), Chinese Academy of
Sciences, Lanzhou 730000, P. R. China
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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10.1002/anie.202005313
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COMMUNICATION
variant I' would compete with the designed intermolecular cy-
cloaddition; 2) a periselectivity issue exists during the intermo-
lecular addition to ketene II depending on the release of CO2 or
not, and the intramolecular allylation step of III (linear versus
branched selectivity); 3) the enantioselective formation of chiral
quaternary stereocenters will also be difficult.[15]
Initially, considering the electronic effect of the amine on the
stability of the carbamate, tosyl (Ts)- and 4-MeO-benzyl (PMB)-
substituted vinyl carbamates 1a’ and 1a were prepared and
tested in the Pd-catalyzed higher-order dipolar cycloaddition with
prepared ketene IIa as the dipolarophile and racemic Monophos
L1 as the ligand. The first reaction only provided an inseparable
mixture of 6- and 8-membered cycloadducts 4aa’ and 5aa’,
neither of which had retained the CO2 unit (Figure 2A). To our
delight, the second reaction did indeed deliver desired 10-
membered monocyclic compound 3aa (as the racemate) in a
good yield (Figure 2B).
in TMCDC reactions were evaluated, but no better results were
observed. For example, when chiral monophosphoramidite
ligands (Figure 3B, L1’, L9-L11) were used, cycloadduct 3aa
was generally obtained with much lower yields and er values;
when other standard bidentate ligands, such as Trost ligand L12
or Paltz ligand L13, were utilized, no reaction occurred. Under
the above reaction conditions, replacing ketene IIa with α-
diazoketone 2a under the irradiation of 6 W blue LEDs was
feasible, and the reaction provided the same product in 49%
NMR yield and 96:4 er (Figure 3C, all-in procedure). Later, a
simple modification of the operation remarkably improved the
yield with the same enantioselectivity (Figure 3C, stepwise, one-
pot procedure: 99% NMR yield and 97% isolated yield, 96:4 er).
A
R
O
L3 (R = Ph, R' = Cy):
86% yield, 86:14 er
L4 (R = 2-Np, R' = Cy):
74% yield, 80:20 er
Ph
N
Ph
Ph
N
Ph
PhO
PhO
P
S
Ph
Ar
P
S
R'
Ar
O
R
(Ar = 4-Br-C6H4)
L5 (R = Ph, R' = Ph):
L2: 95% yield, 14:86 er
88% yield, 87:13 er
A
Pd-catalyzed cycloaddition with N-Ts-substituted vinyl carbomates
L6: 84% yield,
28:72 er
R
O
R
Ph
N
Ph
5 mol%
Pd2(dba)3•CHCl3
20 mol% L1
Ts
N
O
O
Ts
O
O
O
Ph
Me
O
•
L7: 60% yield,
24:76 er
N
Ts
Me
Ph
P
N
S
Cy
Ar
P
S
Cy
Ar
N
O
+
+
O
CH2Cl2, rt
L8: 99% yield,
Ph
Ph
Me
L6/7: R = Ph/H
L8
32% yield
(4aa'/5aa' = 1:1)
96:4 er
Ph
Ph
1a'
IIa
4aa'
5aa'
B
B
Pd-catalyzed cycloaddition with N-PMB-substituted vinyl carbomates
Ph
N
O
O
O
5 mol%
Pd2(dba)3•CHCl3
20 mol% L1
P
N
P
N
P
Ph
PMB
O
Me
O
O
•
O
O
O
N
O
O
Ph
+
O
Ph
O
P
N
CH2Cl2, rt
Me 83% yield
L1': 83% yield, 25:75 er
L9: 46% yield, 49:51 er
L10: 45% yield, 78:22 er
N
Ph
3aa
(racemic)
Ph
L1
O
PMB
Ph
Ph
1a
IIa
(racemic)
O
O
O
O
NH HN
P
N
Figure 2. Preliminary trials on the desirgned reaction. dba: dibenzylideneacetone.
PPh2
N
Ph
N2
O
PPh
2 Ph2P
Ph
tBu
L11: 24% yield, 91:9 er
L12: no reaction
L13: no reaction
Encouraged by the above result, the asymmetric version
was explored by applying chiral P,S ligands that were developed
in our group. As illustrated in Figure 3A, chiral ligand L2 bearing
a biphenyl phosphoramidite unit, which had a good performance
in our previous asymmetric [4+2] dipolar cycloadditions of vinyl
benzoxazinones and ketenes,[11c] can also promote this asym-
metric higher-order cycloaddition in a good efficiency and enan-
tioselectivity (L2: 95% yield, 14:86 er). The use of 3,3’-modified
BINOL-derived P,S ligands L3 and L4, which gave the best
results in our recently reported Pd-catalyzed asymmetric [4+2]
cycloadditions[11f] and Cu-catalyzed asymmetric [3+2] cycloaddi-
tions,[11d] could not provide better results on the enantioselectivi-
ty (L3: 86% yield, 86:14 er; L4: 74% yield, 80:20 er). Next, these
chiral P,S ligands were modified to further improve the stereose-
lectivity. Changing the substituent on the nitrogen atom did not
affect the enantiocontrol (L5: 88% yield, 87:13 er), and removing
the substituents on the 3,3’-positions of the BINOL skeleton or
two phenyl groups of the diphenylethyl skeleton decreased the
enantioselectivities (L6: 84% yield, 28:72 er; L7: 60% yield,
24:76 er). To our surprise, reversing the relative configurations
of the BINOL and diphenylethyl skeletons produced chiral cy-
cloadduct 3aa in an excellent yield and enantioselectivity (L8:
99% yield, 96:4 er). Comparing the enantio-inductions of chiral
ligands L1 and L6-L8, we concluded that both the chirality of the
BINOL and the diphenylethyl skeleton contribute significantly to
the stereoselectivity of the reaction, and the match between
these two different chiral factors is important for high level of
enantiocontrol. Many other standard ligands that are widely used
C
PMB
Ph
Me
O
O
5 mol% Pd2(dba)3•CHCl3
N
12 mol% L8
Me
Ph
O
+
O
Ph
CH2Cl2, rt
6 W blue LEDs
96:4 er
N
O
O
Ph
PMB
3aa
1a
2a
All-in procedure: 49% yield; stepwise, one-pot procedure: 99% yield.
Figure 3. The effect of chiral ligands and procedures on the Pd-catalyzed
asymmetric [8+2] cycloaddition.
With the optimal conditions in hand, the generality of this
catalytic asymmetric [8+2] dipolar cycloaddition was explored.
As highlighted in Table 1, a wide range of vinyl carbamates
bearing different aryl groups could readily participate in this
higher-order dipolar cycloaddition. For example, variation of the
electronic (i.e., H, MeO, F, and Cl) or steric (i.e., t-Bu and Ph)
effect of aryl ring at the para-position were tolerated in the cata-
lytic system, affording the corresponding products in high yields
and er values (Table 1, entries 1-6, 3aa-3fa: 88-97% yields and
96:4-97:3 er). Specifically, vinyl carbamates with sensitive aryl
groups, such as 4-styrenyl, which is prone to polymerization,
were suitable for this cycloaddition (Table 1, entry 7, 3ga: 90%
yield and 95:5 er). Furthermore, variation of the substitution
pattern, for example, 3-OMe- and 3,5-diMe-substituted phenyl
groups as well as β-naphthyl and 3,4-benzodioxolane-fused
systems, was proven compatible, delivering the desired cy-
cloadducts with good reaction efficiencies and high levels of
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10.1002/anie.202005313
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COMMUNICATION
enantiocontrol (Table 1, entries 8-11, 3ha-3ka: 87-93% yields
and 95:5-97:3 er). Vinyl carbamate 1l bearing a heteroaryl moie-
ty, 2-thienyl, was suitable for this reaction, too. Corresponding
cycloadduct 3la was afforded in 86% yield and 94:6 er (Table 1,
entry 12). The success of this asymmetric [8+2] cycloaddition
could be further extended to substrate 1m bearing an unsaturat-
ed vinyl group, albeit with a slightly decreased reaction efficiency
and enantioselectivity (Table 1, entry 13, 3ma:71% yield and
87:13 er). Notably, 2-aryl or alkyl-substituted vinyl carbamates
are not currently applicable in this higher-order cycloaddition.
alkyl groups, such as ethyl, n-butyl, and benzyl ether-containing
propyl groups, were examined, and they led to corresponding
cycloadducts 3am-3ao in 54-94% yields and 95:5-96:4 er values.
While, α-diazoketones bearing alkenyl functional group and 2-
aryl group, cannot participate in this transformation, and it is not
yet clear why. To show the utility of the present methodology, a
gram-scale reaction was performed with substrates 1a and 2a
under the standard conditions. Desired product 3aa can be
obtained in 81% isolated yield with 96:4 er (Eq. 1). Additionally,
the treatment of compound 3aa with trace N-methylpiperidine
under solvent-free conditions at 180 °C for 30 mins produced 8-
membered monocycle 5aa in a moderate yield with retention of
the optical purity (Eq. 2).[18]
Table 1: Scope of the Vinyl Carbomate Partners[a]
Table 2: Scope of the α-Diazoketone Partners[a]
Ar
PMB
O
O
Alk
N2
N
Alk
Ph
O
Pd
O
+
Ar
entry
1
1: R
3
yield (%)[b]
Er[c]
96:4
97:3
96:4
96:4
96:4
96:4
95:5
97:3
95:5
97:3
N
O
O
Ph
PMB
1a: Ph
3aa
3ba
3ca
3da
3ea
3fa
3ga
3ha
3ia
97
95
94
91
97
88
90
93
90
87
1a
2
3
entry
2: Ar, Alk
3
yield(%)[b]
91
Er[c]
95:5
95:5
96:4
95:5
97:3
96:4
94:6
97:3
96:4
96:4
95:5
96:4
95:5
96:4
2
1b: 4-MeO-C6H4
1c: 4-F-C6H4
1d: 4-Cl-C6H4
1e: 4-t-Bu-C6H4
1f: 4-Ph-C6H4
1g: 4-Vinyl-C6H4
1h: 3-MeO-C6H4
1i: 3,5-2Me-C6H3
1j: β-Naphthyl
1
2
2b: 4-Me-C6H4, Me
2c: 4-F-C6H4, Me
2d: 4-Cl-C6H4, Me
2e: 4-Br-C6H4, Me
2f: 4-CO2Me-C6H4, Me
2g: 4-CF3-C6H4, Me
2h: 4-Ph-C6H4, Me
2i: 3-MeO-C6H4, Me
2j: 3-F-C6H4, Me
2k: 3-Cl-C6H4, Me
2l: β-Naphthyl, Me
2m: Ph, Et
3ab
3ac
3ad
3ae
3af
3
91
4
3[d]
4[d]
5[d]
6[d]
7
81
5
72
6
89
7
3ag
3ah
3ai
72
8
90
9
8
92
10
3ja
9[d]
10[d]
11
12
13
14
3aj
70
11
3ka
89
97:3
1k:
3ak
3al
74
12
13
1l: 2-Thienyl
1m: Vinyl
3la
86
71
94:6
90
3ma
87:13
3am
3an
3ao
94
[a]Conditions: irradiate 2a (0.6 mmol) in 1.5 mL of CH2Cl2 with 6 W blue
LEDs at rt for 5 hours, then transfer the generated ketene solution to a
mixture of 1 (0.3 mmol), Pd2(dba)3•CHCl3 (5 mol%) and chiral ligand L8
(12 mol%) in CH2Cl2 (1.5 mL) and stir at rt for another 10 hours. [b]Isolated
yields. [c]Determined by chiral HPLC analysis.
2n: Ph, n-Bu
79
2o: Ph, BnO(CH2)3
54
[a-c]The same with Table 1. [d]Reaction conditions B (all-in operation): mix
Pd2(dba)3•CHCl3 (5 mol%) and chiral ligand L3 (12 mol%) in 1-
chlorobutane/1,2-dichloroethane (3 mL, 1:1) and stir at rt for 30 min, then
introduce 1a (0.3 mmol) and 2 (0.6 mmol) and stir for another 10 hours
under the irradiation of 6 W blue LEDs; others are the same with reaction
conditions A.
Next, the variation of α-diazoketones was studied under the
standard reaction conditions. As shown in Table 2, the introduc-
tion of electronically different substituents at the 4-position of the
phenyl ring was compatible with this catalytic asymmetric [8+2]
cycloaddition, producing enantioenriched 10-membered mono-
cyclic compounds in moderate to high yields with high enanti-
oselectivities (Table 2, entries 1-7, 3ab-3ah: 72-91% yields and
94:6-97:3 er values). Notably, the structure and absolute
configuration of 10-memered product 3ah were unambiguously
established by single-crystal X-ray diffraction; the structures of
other cycloadducts were assigned by analogy.[17] Moreover, α-
diazoketones bearing 3-substituted aryl moieties (Table 2, en-
tries 8-10) or a β-naphthyl group (Table 2, entry 11) were found
to be suitable feedstock for this asymmetric cycloaddition, af-
fording medium-sized cycloadducts in 70-92% yields and with
≥95:5 er values. In addition to methyl, α-diazoketones with other
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10.1002/anie.202005313
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[4]
a) M. Xie, X. Liu, X. Wu, Y. Cai, L. Lin, X. Feng, Angew. Chem. Int. Ed.
2013, 52, 5604-5607; b) R. Mose, G. Preegel, J. Larsen, S. Jakobsen, E.
H. Iversen, K. A. Jørgensen, Nat. Chem. 2017, 9, 487-492.
Furthermore, preliminary density functional theory (DFT) cal-
culations were performed to elucidate the origin of the observed
chemo- and periselectivity.[16] A simplified variant of optimal
ligand L8 (Ph and Cy groups were replaced with Me groups)
was used for the cycloadditions of both vinyl carbamate 1a
(PMB) and 1a’ (Ts). As shown in Figures S2 and S3 in Support-
ing Information, the oxidative addition of the Pd catalyst to sub-
strates 1a and 1a’ is the rate-determined step in each reaction
(for 1a, ∆G = 25.3 kcal/mol; for 1a', ∆G = 21.5 kcal/mol). Fur-
thermore, compared with the nucleophilic addition to the ketene
dipolarophile, it is much more difficult for resulting zwitterionic
intermediate PMP-II to release CO2 (for addition, ∆G = 12.5
kcal/mol; for CO2 release, ∆G = 17.9 kcal/mol), while in the case
of Ts-II, the opposite trend was observed by analyzing the dif-
ference in the activation energies. As illustrated Figure S4, com-
parisons of bond order (BO) and bond length (BL) confirmed that
it is more difficult to break the C-N bond to release CO2 from
[5]
[6]
M. Aginagalde, Y. Vara, A. Arrieta, R. Zangi, V. L. Cebolla, A. Delgado-
Camón, F. P. Cossío, J. Org. Chem. 2010, 75, 2776-2784.
a) Y. Chen, S. Ye, L. Jiao, Y. Liang, D. K. Sinha-Mahapatra, J. W.
Herndon, Z.-X. Yu, J. Am. Chem. Soc. 2007, 129, 10773-10785; b) P.
Roy, B. K. Ghorai, Tetrahedron Lett. 2011, 52, 5668-5671.
[7]
For more catalytic asymmetric [8+2] cycloadditions, see: a) S. Wang, C.
Rodríguez-Escrich, M. A. Pericàs, Angew. Chem. Int. Ed. 2017, 56,
15068-15072, and references therein; b) S. Wang, C. Rodríguez-Escrich,
M. Fianchini, F. Maseras, M. A. Pericàs, Org. Lett. 2019, 21, 3187-3192;
c) C. He, Z. Li, H. Zhou, J. Xu, Org. Lett. 2019, 21, 8022-8026; d) S.
Frankowski, A. Skrzyńska, Ł. Albrecht, Chem. Commun. 2019, 55,
11675-11678.
[8]
[9]
a) B. M. Trost, D. M. T. Chan, J. Am. Chem. Soc. 1979, 101, 6429-6432;
b) I. Shimizu, Y. Ohashi, J. Tsuji, Tetrahedron Lett. 1984, 25, 5183-5186.
Selected reviews on Pd-catalyzed dipolar cycloadditions: a) J. Tsuji,
Tetrahedron 1986, 42, 4361-4401; b) J. D. Weaver, A. Recio, III; A.
J.Grenning, J. A. Tunge, Chem. Rev. 2011, 111, 1846-1913 c) B. D. W.
Allen, C. P. Lakeland, J. P. A. Harrity, Chem. Eur. J. 2017, 23, 13830-
13857; d) N. De, E. J. Yoo, ACS Catal. 2018, 8, 48-58; e) W. Guo, J. E.
Gomez, A. Cristofol, J. Xie, A. W. Kleij, Angew. Chem. Int. Ed. 2018, 57,
13735-13747; f) B. M. Trost, D. L. Van Vranken, Chem. Rev. 1996, 96,
395-422; g) Z. Lu, S. Ma, Angew. Chem. Int. Ed. 2008, 47, 258-297; h) N.
Butt, W. Zhang, Chem. Soc. Rev. 2015, 44, 7929-7967; i) J. Fu, , X. Huo,
B. Li, W. Zhang, Org. Biomol. Chem. 2017, 15, 9747-9759.
PMP-II (BOC-N = 1.1954; BLC-N = 1.44 Å) than from Ts-II (BOC-N
=
0.5844; BLC-N = 1.50 Å). In the case of substrate 1a, two possi-
bilities for the intramolecular allylic alkylation of the adduct of
PMP-II with ketene 2a were investigated: the linear selectivity
leading to the 10-membered cyclic product seems to be favored
over the branched selectivity leading to the 8-membered cyclic
product based on their activation energies (∆G = 5.3 kcal/mol vs
9.0 kcal/mol). These DFT results were in accordance with the
experimentally observed chemo- and periselectivity of these
higher-order cycloadditions of 1a and 1a'.
In conclusion, we have successfully developed the first Pd-
catalyzed asymmetric [8+2] dipolar cycloaddition of vinyl carba-
mates with photogenerated ketenes. This transformation pro-
vides a mild and highly selective protocol for accessing a wide
range of enantioenriched 10-membered monocyclic compounds
with chiral quaternary stereocenters. Moreover, preliminary DFT
calculations were performed to rationalize the high chemo- and
periselectivity. Although further analysis of the stereochemical
outcome is ongoing, this catalytic asymmetric [8+2] dipolar cy-
cloaddition provides a new platform for the higher-order cy-
cloaddition and enantioselective construction of medium-sized
monocyclic architectures.
[10] For selected examples with vinyl carbomates, see: a) J. G. Knight, S. W.
Ainge, A. M. Harm, S. J. Harwood, H. I. Maughan, D. R. Armour, D. M.
Hollinshead, A. A. Jaxa-Chamiec, J. Am. Chem. Soc. 2000, 122, 2944-
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Acknowledgements
We are grateful to the National Science Foundation of China (No.
21822103, 21820102003, 21822303, 21772052, 21772053 and
91956201), the Program of Introducing Talents of Discipline to
Universities of China (111 Program, B17019), the Natural Sci-
ence Foundation of Hubei Province (2017AHB047) and the
International Joint Research Center for Intelligent Biosensing
Technology and Health for support of this research.
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Keywords: [8+2] cycloaddition • medium-sized ring • palladium
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10.1002/anie.202005313
Angewandte Chemie International Edition
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Qun-Liang Zhang, Qin Xiong, Miao-
Miao Li, Wei Xiong, Bing Shi, Yu Lan*,
Liang-Qiu Lu*, and Wen-Jing Xiao
Page No. – Page No
Palladium-Catalyzed Asymmetric [8+2]
Dipolar Cycloadditions of Vinyl
Carbamates and Photogenerated
Ketenes
With the help of visible light irradiation and chiral palladium catalyst, an
enantioselective [8+2] cycloaddition of vinyl carbomates and α‐diazoketones has been
accomplished with high peri‐, chemo‐ and stereoselectivity. This protocol provides an
unprecedented and straightforward route to 10‐membered monocyclic products
bearing chiral quaternary stereocenters under extremely mild conditions (i.e., room
temperature and 6 W blue LEDs).
This article is protected by copyright. All rights reserved.