Visible-Light-Mediated Nitrogen-Centered Radical Strategy: Preparation of 3-Acylated Spiro[4,5]trienones

Article abstract of DOI:10.1002/adsc.202100852

A nitrogen-centered radical strategy for the preparation of 3-acylated spiro[4,5]trienones via visible-light-mediated acylation/ipso-cyclization of alkynes with acyl oxime esters is reported. The alkyl- and aryl-substituted acyl radicals, which generate from the cleavage of carbon-carbon σ-bonds in acyl oxime esters via nitrogen-centered radical pathway, attack the carbon-carbon triple bonds in propiolamides and then undergo ipso-cyclization. This method provides a way for the construction of 3-acyl-substituted spiro[4,5]trienones, which can introduce aryl- or alkyl-substituted acyl into spiro[4,5]trienone skeletons. (Figure presented.).

Full text of DOI:10.1002/adsc.202100852

UPDATES
doi.org/10.1002/adsc.202100852
Visible-Light-Mediated Nitrogen-Centered Radical Strategy:
Preparation of 3-Acylated Spiro[4,5]trienones
Pu Chen,+a Jun Xie,+a Zan Chen,a Bi-Quan Xiong,a Yu Liu,a,* Chang-An Yang,a
and Ke-Wen Tanga
a
Department of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, Hunan 414006,
People’s Republic of China
]
E-mail: liuyu@hnist.edu.cn
+
These authors contributed equally to this work
Manuscript received: July 8, 2021; Revised manuscript received: July 21, 2021;
Version of record online: ■■■, ■■■■
Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.202100852
bonds.[4–5,7–10] For example, Xiao[4] and other
Abstract: A nitrogen-centered radical strategy for
the preparation of 3-acylated spiro[4,5]trienones via
visible-light-mediated acylation/ipso-cyclization of
alkynes with acyl oxime esters is reported. The
chemists[5,7–8] have developed a series of ring-opening
of cycloketone oxime derivatives via NCR strategies.
As shown in Scheme 1, Chen (path I),[11a] Wu (path
II),[11b] Yang (path III),[11c] and Wu’s groups (path
alkyl- and aryl-substituted acyl radicals, which
IV)[11d] have developed NCR mediated cleavage of
generate from the cleavage of carbon-carbon σ-
bonds in acyl oxime esters via nitrogen-centered
radical pathway, attack the carbon-carbon triple
bonds in propiolamides and then undergo ipso-
carbon-carbon single bonds in acyl oxime derivatives.
In these methods, acyl oxime esters were used as acyl
precursors to reat with carbon-carbon double bonds.
However, the strategy employing carbon-carbon triple
cyclization. This method provides a way for the
bonds to carpture the acyl radicals, which generate
construction of 3-acyl-substituted spiro[4,5]
from acyl oxime esters, is lacking.
trienones, which can introduce aryl- or alkyl-
substituted acyl into spiro[4,5]trienone skeletons.
Spirocyclic compounds, such as spiro[4,5]
decatrienones, are important motifs usually encoun-
tered in pharmaceutical molecules and natural
products.[12] Among them, spiroquinones are common
Keywords: nitrogen-centered radical; visible-light-
mediated; acyl oxime esters; acylation/ipso-cycliza-
skeletons that can be applied for the construction of
diverse important structures.[13–14] Thus, many organic
tion; spiro[4,5]trienones
chemists have paied their attention in the development
of convenient and efficient strategies for the prepara-
tion of spiroquinones,[15–18] especially spiro[4,5]
Nitrogen-centered radicals (NCRs), which have the decatrienones.[15c–g,16] The electrophilic ipso-cyclization
same highly reactive as that of the classical carbon- strategies are traditional methods for the construction
based radicals, are a common species in organic
synthesis.[1] Due to the N-substitution and hybridization
patterns, NCRs are usually used as nucleophiles or
electrophiles to go through various radical
reactions.[2–3] Thus, NCR strategies have wide applica-
tions in the synthetic chemistry due to their high
reactivity and efficiency.[4–5] Compared with CCR
(carbon-centered radical) strategies,[6] NCR strategies
can be achieved by avoiding usage of strong oxidants
and high temperatures.[7–8]
In recent years, NCR strategies have been widely
used for the cleavage of carbon-carbon single
Scheme 1. CÀ C bond cleavage of acyl oximes via NCR
strategies.
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of substituted spiro[4,5]decatrienones.[17d–k,18fÀ h] Re-
cently, many chemists, such as Zhang,[15a–d] Zhu,[15e–g]
Qiu,[16] Li,[17] Liang,[18a–d] and our group[18e–h] developed
many oxidative radical cyclization approaches for the
preparation of spiro[4,5]decatrienones. Among these
strategies, 3-acylated spiro[4,5]decatrienones could be
prepared by several different pathways, which used
aldehydes,[17k] ketoacids,[19] acyl chlorides[18f] as acyl
precursors. However, most of these methods only
provided aryl substituted acyl radicals, the alkyl
substituted acyl radicals were quite few.
Table 1. Screening optimal conditions.[a]
Entry Variation from the standard conditions
Isolated
yield (%)
Visible-light-catalysis is a powerful and convenient
method, which is usually employed in organic syn-
thesis and drug synthesis.[20] Visible-light-catalysis
possesses a series of advantages, such as high
efficiency, availability, safety, simple and mild
conditions.[20–21] Herein, we develop a nitrogen-cen-
tered radical strategy for the preparation of 3-acylated
spiro[4,5]trienones via visible-light-mediated acyla-
tion/ipso-cyclization of alkynes with acyl oxime esters,
in which a carbon-carbon σ-bond is severed and two
new carbon-carbon bonds are constructed (Scheme 2).
To obtain the best reaction conditions, we started to
test the reaction between propiolamide 1a (0.2 mmol)
and 3-(4-(trifluoromethyl)benzoyloxyimino)butan-2-
one (2a, 1.5 equiv.) (Table 1). Conducting the reaction
in the presence of Ir(ppy)3 (1 mol%), H2O (3 equiv.),
1
2
3
4
5
6
7
8
9
none
84
58
51
47
43
46
63
53
38
0
2a–1 instead of 2a
2a–2 instead of 2a
2a–3 instead of 2a
2a–4 instead of 2a
2a–5 instead of 2a
2a–6 instead of 2a
2a–7 instead of 2a
2a–8 instead of 2a
10[b] without Ir(ppy)3
11
12
Ir(ppy)3 (2 mol%)
Ru(bpy)3Cl2 (10 mol%) instead of Ir(ppy)3 10
83
13[b] Eosin Y (10 mol%) instead of Ir(ppy)3
14[b] Na2-Eosin Y (10 mol%) instead of Ir(ppy)3
15[b] Mes-Acr+ (2 mol%) instead of Ir(ppy)3
16[b] without additional light
8
6
15
0
44
72
82
9
11
80
78
18
0
58
66
70
25
83
51
17[c]
18[c]
19[c]
36 W compact fluorescent light
3 W blue LED light
12 W blue LED light
°
CH3CN (2 mL) at 80 C irradiated by 5 W blue LED
light for 24 h could form the target product 3aa in
84% yield (entry 1). Next, several other O-benzoic
substrates 2a–1-2a–7, including 4-NO2C6H4CO, 4-
20[b] DMSO instead of CH3CN
21[b] DMF instead of CH3CN
22
23
DCE instead of CH3CN
FC6H4CO,
4-MeC6H4CO,
4-OMeC6H4CO,
2-
nBuOAc instead of CH3CN
NO2C6H4CO, C6F5CO and C6H5CO, were examined
(entries 2–8). The results suggested that different acyl
moieties of the oximes affected the reaction yields
obviously. OÀ 4-CF3 C6H4CO substrate 2a still afforded
the highest yield (entries 2–8 vs entry 1). Additionally,
O-acetic substrate 2a–8 was also suitable for this
transformation, but it could not give higher yield than
that of 2a (entry 9). Conducting the ipso-cyclization
reaction in the absence of Ir(ppy)3 could not form the
target product 3aa (entry 10). Increasing the dosage of
Ir(ppy)3 to 2 mol% afforded the same yield as 1 mol%
of Ir(ppy)3 (entry 11). Then, other phtotocatalysts, such
as Ru(bpy)3Cl2, Eosin Y, Na2-Eosin Y and Mes-Acr+,
were screened (entries 12–15). The reaction yields
showed that Ir(ppy)3 was the best choice. The
acylation/ipso-cyclization transformation could not
24[b] toluene instead of CH3CN
25[d] THF instead of CH3CN
26
27
H2O (1 equiv.)
H2O (5 equiv.)
°
28[b] at 100 C
29[b] at 60 C
°
30
for 48 h
none
31[e]
[a] Reaction conditions: 1a (0.2 mmol), 2a (0.3 mmol,
1.5 equiv.), H2O (3 equiv., 10.8 mg), Ir(ppy)3 (1.3 mg,
1 mol%), CH3CN (2 mL) at 80 C irradiated by 5 W blue
LED light for 24 h.
°
[b] The rest of substrate 1a was recovered.
[c] Instead of 5 W blue LED light.
[d] Most of 1a was decomposed.
[e] 1a (1.0 g, 3.77 mmol), 2a (1.5 equiv.), Ir(ppy)3 (1 mol%),
°
H2O (3 equiv.) and MeCN (40 mL) at 80 C for 64 h.
occur when the reaction was conducted in the absence
of additional light irradiation (entry16). These results
showed that both photocatalyst and visible-light were
indispensable for this NCRs reaction (entries 10 and
16). Next, the test of other different light source
indicated that 5 W blue LED light was suitable light
Scheme 2. NCR strategies for tandem acylation/ipso-cyclization
of alkynes.
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source (entry 17). The solvents screening suggested of substrates could also go through the acylation/ipso-
that none of them gave a better result than that of cyclization smoothly. Propiolamides 1l–v bearing
MeCN (entries 20–25). Employing DCE or nBuOAc as different substituents, including alkyl, phenyl, halo,
solvents could give thefinal product 3aa in 80% and OMe, CF3, and CN groups, on the aromatic ring
78% yields, respectively (entries 22–23). Subsequently, connected with carbon-carbon triple bond were good
the amount of H2O was investigated. We found that candidates (products 3la–va). The steric effect and
H2O was important for the reaction and 3 equiv. of electronic effect of the substituents had important
H2O was beneficial to generate the product (en- effect on the yields of ipso-cyclization products. The
tries 26–27 vs entry 1). Changing the reaction temper- propiolamides bearing para-substituents could afford
°
°
ature to 100 C or 60 C could not afford higher yields higher yields than substrates bearing ortho- and meta-
(entries 28–29). A longer reaction time could also not substituents (products 3la, 3ma and 3oa). The
furnish a higher the reaction yield (entry 30). An propiolamides bearing electron-withdrawing substitu-
amplified experiment could generate the product 3aa ents provided lower yields than substrates bearing
in moderate yield (entry 31).
electron-donating substituents. The propiolamides 1w
Based on the acquired standard conditions, we (R1 =naphthyl) and 1x (R1 =thienyl) could furnish the
began to examine the scope of propiolamides 1 in the ipso-cyclization products 3wa and 3xa in moderate
presence of acyl oxime ester 2a (Table 2). First, yields. However, the alkyl-substituted alkynes 1y–z
several kinds of propiolamides 1a–e bearing different and terminal alkyne 1aa could not undergo the
substituents on N atom were tested. All of them could acylation/ipso-cyclization under the standard condi-
afford the corresponding products 3aa–ea in 70–84% tions with most of the starting materials decomposed
yields. However, the substrate 1f bearing a H on the N (products 3ya–aaa).
atom could not undergo this ipso-cyclization and most
After the investigation of propiolamides, we next
of the starting materials were recovered (product 3fa). examined the scope of acyl oxime esters 2 in the
Next, we investigated the propiolamides 1g–k bearing presence of propiolamide 1a (Table 3). For R5=Me, a
different substituents on the N-aryl moiety. This type variety of different acyl oxime esters 2b–g bearing
alkyl groups on the acyl moieties, including Et, nPr, iPr,
nBu, nC5H11 and 2-methylbutyl, were researched. All of
Table 2. Scope of propiolamides (1).[a]
Table 3. Scope of acyl oxime esters (2).[a]
[a] Reaction conditions: 1 (0.2 mmol), 2a (1.5 equiv.), H2O
°
(3 equiv.), Ir(ppy)3 (1 mol%), CH3CN (2 mL) at 80 C
irradiated by 5 W blue LED light for 24 h.
[b] Most of the substrate 1 was recovered.
[c] Most of the substrate 1 was decomposed.
[a] Reaction conditions: 1a (0.2 mmol), 2 (1.5 equiv.), H2O
°
(3 equiv.), Ir(ppy)3 (1 mol%), CH3CN (2 mL) at 80 C
irradiated by 5 W blue LED light for 24 h.
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them could generate the 3-acylated spiro[4,5]trienones Scheme 3). The results indicated that H2O offered an O
3ab–ag in 70–80% yields. Aryl-substituted acyl oxime atom for building carbonyl group.
esters 2h–n were also suitable for this ipso-cyclization,
The 2-IBn substituted ipso-product 3ca could
affording the target products 3ah–an in moderate undergo intramolecular Heck reaction to afford aza-
yields. The thienyl-substituted acylation product 3ao quaternary tricyclic product
could be furnished from propiolamide 1a and 1- (Scheme 4).[17j]
6
in 70% yield
(thiophen-2-yl)-2-(4-(trifluoromethyl)
Based on the above results and existing
benzoyloxyimino)propan-1-one 2o. For R5=Et, three literature,[11,16–18,20À 22] we propose a plausible mecha-
acyl oxime esters 2p–r were screened and offered the nism for the acylation/ipso-cyclization of alkynes with
corresponding products 3ab, 3ac and 3ah in 77%, acyl oxime esters via visible-light-mediated nitrogen-
71% and 70% yields, respectively.
centered radical pathway (Scheme 5). As irradiated by
To obtain a deeper insight of the mechanism of the visible-light, Ir3+ is tansformed into Ir3+*. The photo-
acylation/ipso-cyclization, several control experiments excited Ir3+* gives a single electron to acyl oxime ester
were conducted (Scheme 3). The reactions between 2a, to form the radical anion A and Ir4+. Then, the
propiolamide 1a and acyl oxime ester 2, which were intermediate A decomposes into ROÀ and iminyl
carried out under the best conditions in the presence of radical B, which deliveres acyl radical C and
BHT, TEMPO or 1,1-diphenylethene as radical inhib- acetonitrile.[11] The substrate 1a converts into benzyl
itors, were suppressed (eqs 1–3, Scheme 3). As em- radical D via the addition of the intermediate C to the
ploying TEMPO in the reaction, the acyl captured carbon-carbon triple bond of 1a. The intermediate D
product 4 could be isolated in 46% yield (eq 2, undergoes ipso-cyclization to furnish the radical E,
Scheme 3). The acyl-trapping product 5 could be which goes through SET to afford the carbocation F
obtained in 44% when 1,1-diphenylethene was used in under the oxidation of Ir4+, regenerating Ir3+. The
the reaction (eq 3, Scheme 3). Then, the reaction hydroxide ion, which comes from H2O under the action
between 1a and 2a was conducted in the presence of ROÀ , attacks the carbocation F to assemble the
18
Ir(ppy)3 (1 mol%), H2 O (3 equiv.), CH3CN (2 mL) at intermediate G.[17d–k,18fÀ h] The intermediate G occurrs
80 C irradiated by 5 W blue LED light for 24 h (eq 4, release of OMeÀ and H+ to provide the target product
°
3aa.
In conclusion, we have reported a nitrogen-centered
radical strategy for the preparation of 3-acylated spiro
[4,5]trienones via visible-light-mediated acylation/
ipso-cyclization of alkynes with acyl oxime esters. The
alkyl- or aryl-substituted acyl radicals, which generate
from the cleavage of carbon-carbon σ-bonds in acyl
oxime esters via nitrogen-centered radical pathway,
attack the carbon-carbon triple bonds in propiolamides
and then undergo ipso-cyclization. This method pro-
vides a way for the construction of 3-acyl-substituted
spiro[4,5]trienones, which can introduce aryl- or alkyl-
Scheme 3. Control Experiments.
Scheme 4. Applications.
Scheme 5. Possible Mechanisms.
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Lett. 2017, 19, 3620–3623; d) X.-Q. Hu, J.-R. Chen, Q.
Wei, F.-L. Liu, Q.-H. Deng, A.-M. Beauchemin, W.-J.
Xiao, Angew. Chem. Int. Ed. 2014, 53, 12163–12167;
Angew. Chem. 2014, 126, 12359–12363; e) J. Chen, H.-
M. Guo, Q.-Q. Zhao, J.-R. Chen, W.-J. Xiao, Chem.
Commun. 2018, 54, 6780–6783; f) H. Kim, T. Kim, D.-
G. Lee, S.-W. Roh, C. Lee, Chem. Commun. 2014, 50,
9273–9276.
substituted acyl into spiro[4,5]trienone skeletons. The
further study and application of nitrogen-centered
radical strategy are currently undergoing in our
laboratory.
Experimental Section
Typical Experimental Procedure for the Synthesis
of 3-Acylated Spiro[4,5]trienones
[4] a) B. Lu, Y. Cheng, L.-Y. Chen, J.-R. Chen, W.-J. Xiao,
ACS Catal. 2019, 9, 8159–8164; b) X.-Y. Yu, J.-R. Chen,
P.-Z. Wang, M.-N. Yang, D. Liang, W.-J. Xiao, Angew.
Chem. Int. Ed. 2018, 57, 738–743; Angew. Chem. 2018,
130, 746–751; c) X.-S. Zhou, Y. Cheng, J. Chen, X.-Y.
Yu, W.-J. Xiao, J.-R. Chen, Angew. Chem. Int. Ed. 2019,
11, 5300–5305; d) B.-Q. He, X.-Y. Yu, P.-Z. Wang, J.-R.
Chen, W.-J. Xiao, Chem. Commun. 2018, 54, 12262–
12265; e) J. Chen, P.-Z. Wang, B. Lu, D. Liang, X.-Y.
Yu, W.-J. Xiao, J.-R. Chen, Org. Lett. 2019, 21, 9763–
9768; f) J. Chen, B.-Q. He, P.-Z. Wang, X.-Y. Yu, Q.-Q.
Zhao, J.-R. Chen, W.-J. Xiao, Org. Lett. 2019, 21, 4359–
4364.
[5] a) T. Nishimura, T. Yoshinaka, Y. Nishiguchi, Y. Maeda,
S. Uemura, Org. Lett. 2005, 7, 2425–2427; b) T.
Nishimura, S. Uemura, J. Am. Chem. Soc. 2000, 122,
12049–12050; c) H.-B. Yang, N. Selander, Chem. Eur. J.
2017, 23, 1779–1783; d) H.-B. Yang, S. R. Pathipati, N.
Selander, ACS Catal. 2017, 7, 8441–8455; e) Y.-Q. Tang,
J.-C. Yang, L. Wang, M.-J. Fan, L.-N. Guo, Org. Lett.
2019, 21, 5178–5182; f) J. Wu, J.-Y. Zhang, P. Gao, S.-
L. Xu, L.-N. Guo, J. Org. Chem. 2018, 83, 1046–1055.
[6] a) I.-B. Krylov, O.-O. Segida, A.-S. Budnikov, A.-O.
Terent’ev, Adv. Synth. Catal. 2021, 363, 2502–2528;
b) C. Chen, J. Zhao, X. Shi, L. Liu, Y.-P. Zhu, W. Sun,
B. Zhu, Org. Chem. Front. 2020, 7, 1948–1969; c) F.
Xiao, Y. Guo, Y.-F. Zeng, Adv. Synth. Catal. 2021, 363,
120–143; d) T. Xiao, H. Huang, D. Anand, L. Zhou,
Synthesis 2020, 52, 1585–1601; e) X.-Y. Yu, J.-R. Chen,
W.-J. Xiao, Chem. Rev. 2021, 121, 506–561; f) S.
Murarka, Adv. Synth. Catal. 2018, 360, 1735–1753; g) P.
Niu, J. Li, Y. Zhang, C. Huo, Eur. J. Org. Chem. 2020,
36, 5801–5814; h) S.-Q. He, H.-C. Li, X.-L. Chen, I.-B.
Krylov, A.-O. Terent’ev, L.-B. Qu, B. Yu, Chin. J. Org.
Chem. 2021, 41. doi: 10.6023/cjoc202105041.
[7] a) J.-J. Zhang, X.-H. Duan, Y. Wu, J.-C. Yang, L.-N.
Guo, Chem. Sci. 2019, 10, 161–166; b) J. Lou, Y. He, Y.-
L. Li, Z.-K. Yu, Adv. Synth. Catal. 2019, 361, 3787–
3799; c) Y. He, J. Lou, K.-K. Wu, H.-M. Wang, Z.-K.
Yu, J. Org. Chem. 2019, 84, 2178–2190; d) Z.-P. Yin, J.
Rabeah, A. Bruckner, X.-F. Wu, ACS Catal. 2018, 8,
10926–10930; e) Z.-P. Yin, J. Rabeah, A. Bruckner, X.-
F. Wu, Org. Lett. 2019, 21, 1766–1769.
[8] a) J.-X. Xu, F. Teng, J.-N. Xiang, W. Deng, J.-H. Li,
Org. Lett. 2019, 21, 9434–9437; b) Y. Liu, Q.-L. Wang,
Z. Chen, H. Li, B.-Q. Xiong, P.-L. Zhang, K.-W. Tang,
Chem. Commun. 2020, 56, 3011–3014; c) Z. Chen, Q.
Zhou, Q.-L. Wang, P. Chen, B.-Q. Xiong, Y. Liang, K.-
W. Tang, Y. Liu, Adv. Synth. Catal. 2019, 362, 3004–
3010; d) P. Chen, Z. Chen, B.-Q. Xiong, Y. Liang, K.-W.
To a Schlenk tube were added propiolamides 1 (0.2 mmol,
0.1 M), acyl oxime esters compounds 2 (1.5 equiv.), Ir(ppy)3
°
(1 mol%), H2O (3 equiv.) and MeCN (2 mL) at 80 C under
irradiation of 5 W blue light for 24 h. Until complete
consumption of the starting material was observed by TLC and/
or GC-MS analysis. After the reaction was finished, the reaction
mixture removal of the solvent, the crude product was purified
by column chromatography (petroleum ether/ethyl acetate, 3:1)
to provide the desired products 3. A scaled-up experiment
conducted in the presence of 1a (1 g, 3.77 mmol), 2a
(1.5 equiv.), Ir(ppy)3 (1 mol%), H2O (3 equiv.) and MeCN
°
(40 mL) at 80 C under irradiation of 5 W blue light for 64 h
gave the target product 3aa in 51% yield (563.6 mg).
Acknowledgements
We thank the National Natural Science Foundation of China
(No. 22078084 and 51874132), Scientific Research Fund of
Hunan Provincial Education Department (No. 20 A224 and
18 A319), Science and Technology Planning Project of Hunan
Province (No. 2020RC3056 and 2018TP1017) and Natural
Science Foundation of Hunan Province (No. 2020JJ5221 and
2020JJ5212) for financial support.
References
[1] a) S.-Z. Zard, Chem. Soc. Rev. 2008, 37, 1603–1618;
b) J.-R. Chen, X.-Q. Hu, L.-Q. Lu, W.-J. Xiao, Chem.
Soc. Rev. 2016, 45, 2044–2056; c) T. Xiong, Q. Zhang,
Chem. Soc. Rev. 2016, 45, 3069–3087; d) J. Davies, S. P.
Morcillo, J. J. Douglas, D. Leonori, Chem. Eur. J. 2018,
24, 12154–12163; e) M. D. Kärkäs, ACS Catal. 2017, 7,
4999–5022; f) Y. Zhao, W. Xia, Chem. Soc. Rev. 2018,
47, 2591–2608.
[2] a) Z. Hu, L. Fu, P. Chen, W. Cao, G. Liu, Org. Lett.
2021, 23, 129–134; b) E.-C. Gentry, R.-R. Knowles, Acc.
Chem. Res. 2016, 49, 1546–1556; c) Y. Zhang, S. Zhang,
Z. Sun, K. He, Q. Chen, Y. Yuan, X. Jia, J. Org. Chem.
2019, 84, 14202–14208; d) H. Chen, W. Jin, S. Yu, Org.
Lett. 2020, 22, 5910–5914; e) W. Shang, C. Zhu, F.
Peng, Z. Pan, Y. Ding, C. Xia, Org. Lett. 2021, 23, 1222–
1227; f) X.-D. An, Y.-Y. Jiao, H. Zhang, Y. Gao, S. Yu,
Org. Lett. 2018, 20, 401–404.
[3] a) Q.-Q. Zhao, J. Chen, X.-S. Zhou, X.-Y. Yu, J.-R.
Chen, W.-J. Xiao, Chem. Eur. J. 2019, 25, 8024–8029;
b) Q.-Q. Zhao, X.-Q. Hu, M.-N. Yang, J.-R. Chen, W.-J.
Xiao, Chem. Commun. 2016, 52, 12749–12752; c) Q.-Q.
Zhao, J. Chen, D.-M. Yan, J.-R. Chen, W.-J. Xiao, Org.
Adv. Synth. Catal. 2021, 363, 1–8
5
© 2021 Wiley-VCH GmbH
��
These are not the final page numbers!

UPDATES
asc.wiley-vch.de
Tang, J. Xie, Y. Liu, Org. Biomol. Chem. 2021, 19,
3181–3190.
1360; c) M.-G. Donahue, N.-G. Jentsch, E.-C. Realini,
Tetrahedron Lett. 2017, 58, 3219–3222; d) A. Verma, L.-
S. Banjara, R. Meena, S. Kumar, Asian J. Org. Chem.
2020, 9, 105–110; e) R. Pan, L. Hu, C. Han, A. Lin, H.
Yao, Org. Lett. 2018, 20, 1974–1977; f) W. Dong, L. Qi,
J.-Y. Song, J.-M. Chen, J.-X. Guo, S. Shen, L.-J. Li, W.
Li, L.-J. Wang, Org. Lett. 2020, 22, 1830–1835; g) P.
Qian, B. Du, R. Song, X. Wu, H. Mei, J. Han, Y. Pan, J.
Org. Chem. 2016, 81, 6546–6553.
[9] a) Q.-Q. Zhao, M. Li, X.-S. Xue, J.-R. Chen, W.-J. Xiao,
Org. Lett. 2019, 21, 3861–3865; b) L.-Q. Nguyen, R.-R.
Knowles, ACS Catal. 2016, 6, 2894–2903; c) M.-D.
Abreu, M. Selkti, P. Belmontand, E. Brachet, Adv. Synth.
Catal. 2020, 362, 2216–2222; d) J. Davies, S.-G. Booth,
S. Essafi, R.-A.-W. Dryfe, D. Leonori, Angew. Chem. Int.
Ed. 2015, 54, 14017–14021; Angew. Chem. 2015, 127,
14223–14227; e) J. Hioe, D. Šakić, V. Vrček, H. Zipse, [15] a) W. Dong, Y. Yuan, C. Liang, F. Wu, S. Zhang, X. Xie,
Org. Biomol. Chem. 2015, 13, 157–169.
Z. Zhang, J. Org. Chem. 2021, 86, 3697–3705; b) W.
Dong, Y. Yuan, X. Gao, M. Keranmu, W. Li, X. Xie, Z.
Zhang, J. Org. Chem. 2019, 84, 1461–1467; c) W. Dong,
Y. Yuan, X. Gao, M. Keranmu, W. Li, X. Xie, Z. Zhang,
Org. Lett. 2018, 20, 5762–5765; d) W. Dong, Y. Yuan,
X. Xie, Z. Zhang, Org. Lett. 2020, 22, 528–532; e) Z.
Gu, H. Zhang, P. Xu, Y. Cheng, C. Zhu, Adv. Synth.
Catal. 2015, 357, 3057–3063; f) H. Zhang, Z. Gu, P. Xu,
H. Hu, Y. Cheng, C. Zhu, Chem. Commun. 2016, 52,
477–480; g) H. Zhang, C. Zhu, Org. Chem. Front. 2017,
4, 1272–1275.
[10] a) E. Brachet, L. Marzob, M. Selktic, B. König, P.
Belmont, Chem. Sci. 2016, 7, 5002–5006; b) A.-M.
Carestia, D. Ravelli, E.-J. Alexanian, Chem. Sci. 2018, 9,
5360–5365; c) X.-Q. Hu, J. Chen, J.-R. Chen, D.-M.
Yan, W.-J. Xiao, Chem. Eur. J. 2016, 22, 14141–14146;
d) A.-J. Musacchio, L.-Q. Nguyen, G.-H. Beard, R.-R.
Knowles, J. Am. Chem. Soc. 2014, 136, 12217–12220;
e) Z. Li, J.-P. Cheng, J. Org. Chem. 2003, 68, 7350–
7360.
[11] a) B.-Q. He, Y. Gao, P.-Z. Wang, H. Wu, H.-B. Zhou, X.-
P. Liu, J.-R. Chen, Synlett. 2021, 32, 373–377; b) X. Fan, [16] a) Y. He, G. Qiu, Org. Biomol. Chem. 2017, 15, 3485–
T. Lei, B. Chen, C.-H. Tung, L.-Z. Wu, Org. Lett. 2019,
21, 4153–4158; c) L. Zheng, P.-J. Xia, Q.-L. Zhao, Y.-E.
3490; b) G. Qiu, Z.-F. Chen, W. Xie, H. Zhou, Eur. J.
Org. Chem. 2019, 2019, 4327–4333.
Qian, W.-N. Jiang, H.-Y. Xiang, H. Yang, J. Org. Chem. [17] a) M. Hu, J.-H. Fan, Y. Liu, X.-H. Ouyang, R.-J. Song,
2020, 85, 11989–11996; d) Y.-Y. Cheng, T. Lei, L. Su, X.
Fan, B. Chen, C.-H. Tung, L.-Z. Wu, Org. Lett. 2019, 21,
8789–8794.
J.-H. Li, Angew. Chem. Int. Ed. 2015, 54, 9577–9580;
Angew. Chem. 2015, 127, 9713–9716; b) H.-Y. Liu, Y.
Lu, Y. Li, J.-H. Li, Org. Lett. 2020, 22, 8819–8823;
c) M. Hu, L.-Y. Guo, Y. Han, F.-L. Tan, R.-J. Song, J.-H.
Li, Chem. Commun. 2017, 53, 6081–6084; d) P.-C. Qian,
Y. Liu, R.-J. Song, J.-N. Xiang, J.-H. Li, Synlett. 2015,
26, 1213–1216; e) W.-T. Wei, R.-J. Song, X.-H. Ouyang,
Y. Li, H.-B. Li, J.-H. Li, Org. Chem. Front. 2014, 1,
484–489; f) X.-H. Ouyang, R.-J. Song, B. Liu, J.-H. Li,
Chem. Commun. 2016, 52, 2573–2576; g) L.-J. Wu, F.-
L. Tan, M. Li, R.-J. Song, J.-H. Li, Org. Chem. Front.
2017, 4, 350–353; h) X.-H. Yang, X.-H. Ouyang, W.-T.
Wei, R.-J. Song, J.-H. Li, Adv. Synth. Catal. 2015, 357,
1161–1166; i) M. Li, R.-J. Song, J.-H. Li, Chin. J. Chem.
2017, 35, 299–302; j) B.-X. Tang, Y.-H. Zhang, R.-J.
Song, D.-J. Tang, G.-B. Deng, Z.-Q. Wang, Y.-X. Xie,
Y.-Z. Xia, J.-H. Li, J. Org. Chem. 2012, 77, 2837–2849;
k) X.-H. Ouyang, R.-J. Song, Y. Li, B. Liu, J.-H. Li, J.
Org. Chem. 2014, 79, 4582–4589.
[12] a) C.-H. Heathcock, S.-L. Graham, M.-C. Pirrung, F.
Plavac, C.-T. White, The Total Synthesis of Natural
Products, Vol. 5 Apsimon, J., Ed.; Wiley-Interscience:
New York 1983, 1; b) K. Yoneda, E. Yamagata, T.
Nakanishi, T. Nagashima, I. Kawasaki, T. Yoshida, H.
Mori, I. Miura, Phytochemistry 1984, 23, 2068–2069;
c) Y.-S. Cai, Y.-W. Guo, K. Krohn, Nat. Prod. Rep. 2010,
27, 1840–1870; d) W.-T. Wu, L. Zhang, S.-L. You,
Chem. Soc. Rev. 2016, 45, 1570–1580; e) R. Ramon,
Chem. Soc. Rev. 2012, 41, 1060–1074; f) Y.-L. Yang, F.-
R. Chang, Y.-C. Wu, Helv. Chim. Acta. 2004, 87, 1392–
1399; g) Z. Jin, Nat. Prod. Rep. 2005, 22, 111–126;
h) V.-A. D’yakonov, O.-A. Trapeznikova, A.-D. Meijere,
U.-M. Dzhemilev, Chem. Rev. 2014, 114, 5775–5814.
[13] a) Z.-Q. Wang, B.-X. Tang, H.-P. Zhang, F. Wang, J.-H.
Li, Synthesis 2009, 2009, 891–902; b) F.-G.-L. Turiso,
Org. Lett. 2005, 7, 151–154; c) W. Wei, H.-H. Cui, D.-S. [18] a) D.-P. Jin, P. Gao, D.-Q. Chen, S. Chen, J. Wang, X.-Y.
Yang, H.-L. Yue, C.-L. He, Y.-L. Zhang, H. Wang, Green
Chem. 2017, 19, 5608–5613; d) H.-H. Cui, W. Wei, D.-
S. Yang, J.-M. Zhang, Z.-H. Xu, J.-W. Wen, H. Wang,
RSC Adv. 2015, 5, 84657–84661; e) Y. Zhou, X. Zhang,
Y. Zhang, L.-X. Ruan, J.-C. Zhang, D. Zhang-Negrerie,
Y.-F. Du, Org. Lett. 2017, 19, 150–153; f) T. Liu, Y. Li,
L. Jiang, J. Wang, K. Jin, R. Zhang, C. Duan, Org.
Biomol. Chem. 2020, 18, 1933–1939.
Liu, Y.-M. Liang, Org. Lett. 2016, 18, 3486–3489; b) L.-
J. Wang, A.-Q. Wang, Y. Xia, X.-X. Wu, X.-Y. Liu, Y.-
M. Liang, Chem. Commun. 2014, 50, 13998–14001;
c) Z.-Z. Zhou, L. Zheng, X.-B. Yan, D.-P. Jin, Y.-T. He,
Y.-M. Liang, Org. Biomol. Chem. 2016, 14, 4507–4510;
d) H.-L. Hua, Y.-T. He, Y.-F. Qiu, Y.-X. Li, B. Song, P.
Gao, X.-R. Song, D.-H. Guo, X.-Y. Liu, Y.-M. Liang,
Chem. Eur. J. 2014, 21, 1468–1473; e) Y. Liu, J.-L.
Zhang, M.-B. Zhou, R.-J. Song, J.-H. Li, Chem.
Commun. 2014, 50, 14412–14414; f) Y. Liu, Q.-L.
Wang, C.-S. Zhou, B. Xiong, P.-L. Zhang, C.-A. Yang,
K.-W. Tang, J. Org. Chem. 2018, 83, 2210–2218; g) Y.
Liu, Q.-L. Wang, B.-Q. Xiong, P.-L. Zhang, C.-A. Yang,
[14] a) S. Manna, P.-K.-S. Ashwathappa, K.-R. Prabhu,
Chem. Commun. 2020, 56, 13165–13168; b) H.-E. Ho,
A. Pagano, J.-A. Rossi-Ashton, J.-R. Donald, R.-G.
Epton, J.-C. Churchill, M.-J. James, P. O’Brien, R.-J.-K.
Taylor, W.-P. Unsworth, Chem. Sci. 2020, 11, 1353–
Adv. Synth. Catal. 2021, 363, 1–8
6
© 2021 Wiley-VCH GmbH
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These are not the final page numbers!

UPDATES
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Y.-X. Gong, J. Liao, Q. Zhou, Synlett. 2018, 29, 2396– [21] a) Q. L. Wang, W.-Z. Zhang, Q. Zhou, C.-S. Zhou, B.-Q.
2403; h) Y. Liu, Q.-L. Wang, Z. Chen, Q. -Zhou, B.-Q.
Xiong, P.-L. Zhang, K.-W. Tang, Chem. Commun. 2019,
55, 12212–12215.
Xiong, K.-W. Tang, Y. Liu, Org. Biomol. Chem. 2019,
17, 7918–7926; b) Y. Liu, Z. Chen, Q.-L. Wang, P. Chen,
J. Xie, B. Xiong, P.-L. Zhang, K.-W. Tang, J. Org. Chem.
2020, 85, 2385–2394; c) Y. Liu, Q.-L. Wang, Z. Chen, P.
Chen, K.-W. Tang, Q. Zhou, J. Xie, Org. Biomol. Chem.
2019, 17, 10020–10029; d) Y. Liu, Q.-L. Wang, Z. Chen,
Q. Zhou, H. Li, C.-S. Zhou, B.-Q. Xiong, P.-L. Zhang,
K.-W. Tang, J. Org. Chem. 2019, 84, 2829–2839.
[19] a) C.-R. Reddy, D.-H. Kolgave, M. Subbarao, M. Aila,
S.-K. Prajapti, Org. Lett. 2020, 22, 5342–5346; b) A.-M.
Nair, A.-H. Shinde, S. Kumar, C.-M.-R. Volla, Chem.
Commun. 2020, 56, 12367–12370; c) H.-L. Zhu, F.-L.
Zeng, X.-L. Chen, K. Sun, H.-C. Li, X.-Y. Yuan, L.-B.
Qu, B. Yu, Org. Lett. 2021, 23, 2976–2980.
[20] a) B.-G. Cai, Z.-L. Chen, G.-Y. Xu, J. Xuan, W.-J. Xiao,
Org. Lett. 2019, 21, 4234–4238; b) H.-H. Zhang, J.-J.
Zhao, S.-Y. Yu, J. Am. Chem. Soc. 2018, 140, 16914–
16919; c) J.-J. Zhao, H.-H. Zhang, X. Shen, S.-Y. Yu,
Org. Lett. 2019, 21, 913–916; d) X. Wang, Y.-F. Han, X.-
H. Ouyang, R.-J. Song, J.-H. Li, Chem. Commun. 2019,
55, 14637–14640.
[22] a) X.-Y. Yu, Q.-Q. Zhao, J. Chen, W.-J. Xiao, J.-R. Chen,
Acc. Chem. Res. 2020, 53, 1066–1083; b) W. Yin, X.
Wang, New J. Chem. 2019, 43, 3254–3264; c) S.-B.
Höfling, M.-R. Heinrich, Synthesis 2011, 2, 173–189;
d) W.-C. Yang, M.-M. Zhang, J.-G. Feng, Adv. Synth.
Catal. 2015, 362, 4446–4461.
Adv. Synth. Catal. 2021, 363, 1–8
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Visible-Light-Mediated Nitrogen-Centered Radical Strategy:
Preparation of 3-Acylated Spiro[4,5]trienones
Adv. Synth. Catal. 2021, 363, 1–8
P. Chen, J. Xie, Z. Chen, B.-Q. Xiong, Y. Liu*, C.-A. Yang,
K.-W. Tang