Divergent Synthesis of Aziridine and Imidazolidine Frameworks under Blue LED Irradiation

Article abstract of DOI:10.1021/acs.orglett.1c00979

We develop a visible light-promoted divergent cycloaddition of α-diazo esters with hexahydro-1,3,5-triazines, leading to a series of aziridine and imidazolidine frameworks in average good yield, by simply changing the reaction media used. It is noteworthy that the reaction occurs under sole visible light irradiation without the need for exogenous photoredox catalysts. More significantly, a reasonable reaction mechanism was proposed on the basis of the control experiments and density functional theory calculation results.

Full text of DOI:10.1021/acs.orglett.1c00979

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Letter
Divergent Synthesis of Aziridine and Imidazolidine Frameworks
under Blue LED Irradiation
Xiao Cheng,∥ Bao-Gui Cai,∥ Hui Mao,∥ Juan Lu, Lei Li, Kun Wang,* and Jun Xuan*
Cite This: Org. Lett. 2021, 23, 4109−4114
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ABSTRACT: We develop a visible light-promoted divergent
cycloaddition of α-diazo esters with hexahydro-1,3,5-triazines,
leading to a series of aziridine and imidazolidine frameworks in
average good yield, by simply changing the reaction media used. It
is noteworthy that the reaction occurs under sole visible light
irradiation without the need for exogenous photoredox catalysts.
More significantly, a reasonable reaction mechanism was proposed
on the basis of the control experiments and density functional
theory calculation results.
early 2013, the group of Cho developed a visible light-
ziridines are some of the smallest nitrogen-containing
Aheterocycles that can be widely found in various natural promoted aminofluoroalkylation of allylic amines for the
synthesis of CF3-containing aziridines with [Ru(bpy)3]Cl2 as
the photoredox catalyst.5 Visible light-induced olefin aziridi-
nation6 and aza-Darzens reaction7 are alternative methods for
the synthesis of these valuable building blocks. Recently, the
Lambert group disclosed a vicinal C−H diamination reaction
for the formation of aziridine derivatives through an electro-
photocatalytic strategy.8 Though elegant advances in light-
induced synthesis of aziridines have been achieved, current
methodologies still depend on metal-based or organic dye
photoredox catalysts. On the contrary, the growing demand for
sustainable chemistry makes development of versatile methods
for the construction of both aziridines and other important
heterocyclic systems from same easily accessed starting
materials under benign conditions still urgent.
isolates, pharmaceuticals, and biologically active molecules
(Scheme 1A).1 Moreover, aziridines are also known as highly
versatile synthetic intermediates to undergo ring-opening
functionalization due to their intrinsic ring strain.2 Despite
the fact that syntheses of aziridines have been extensively
developed in the past several decades,3 visible light-catalyzed
synthesis of three-membered heterocyclic frameworks as a
clean and sustainable route is rarely reported (Scheme 1B).4 In
Scheme 1. Biologically Relevant Compounds Containing
Aziridine Motifs and Their Photopromoted Synthetic
Methods
Since they were first discovered by Reinfield et al. at the
beginning of the past century,9 hexahydro-1,3,5-triazines have
been recognized as efficient 1,m-dipoles in the synthesis of
various important N-containing heterocycles through a cyclo-
addition process.10 Among the reactions developed, α-diazo
esters proved to be ideal cycloaddition partners with
hexahydro-1,3,5-triazines in the presence of Lewis acids or
transition metals.11 Despite the fact that metal-catalyzed
carbene-transfer reactions from α-diazo esters have been
widely investigated for several decades,12 visible light-
promoted carbene generation/functionalization of α-diazo
Received: March 23, 2021
Published: May 14, 2021
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© 2021 American Chemical Society
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esters emerged in only 2018. Under blue LED irradiation, α-
diazo esters can be activated by absorption of light in the
visible region to form free singlet carbene species through
nitrogen gas extrusion.13 The groups of Davis, Zhou, Koenigs,
Xiao, and many others have successfully applied this strategy to
various chemical transformations, such as X−H insertion,14
cyclopropanation and cyclopropenation,15 Doyle−Kirmse
reaction,16 and other valuable reactions.17 Compared with
these well-developed processes, the applications of photo-
generated carbene species using visible light from α-diazo
esters toward the synthesis of important heterocyclic
compounds are rarely reported.18
As part of our ongoing research interest in the development
of heterocycle-oriented methodologies,19 we herein report a
solvent-controlled divergent cycloaddition of α-diazo esters
with hexahydro-1,3,5-triazines promoted by visible light
(Scheme 1c). It was found that aziridine derivatives were
accessed in DMSO with good results. This method can also be
applied to the facile synthesis of imidazolidine frameworks in
DCM media. Appealing features of this protocol include (1)
the use of visible light as a sole clean energy source, (2) the
fact that exogenous photoredox catalysts are not required to
run the process, and (3) the fact that both aziridines and
imidazolidines can be easily accessed through simple
alternation of the reaction solvents used.
We initially optimized the reaction conditions by reacting
phenyldiazoacetate 1 and PMP-substituted hexahydro-1,3,5-
triazine 2 in DMSO under blue LED irradiation. It was found
that aziridine 3 could be obtained in 85% yield of the isolated
product by using 3.0 equiv of 1 (compared with the in situ-
formed formaldimine from 2). Under the optimal reaction
conditions (for details of the optimization, see the Supporting
Information), the generality and the limitation of visible light-
promoted formal [2+1] cycloaddition were then investigated
(Scheme 2). First, a wide range of mono- or disubstituted α-
diazo esters were examined. α-Diazo esters with different
electron-donating substituents (methyl and acyloxyl) or
electron-withdrawing groups (halogens, e.g., -F, -Cl, or -Br)
transformed to the corresponding formal [2+1] cycloaddition
products in good to high yields (Table 1 in the Supporting
Information, 3−10 and 12). The yields of heterocycles
produced from meta- and ortho-substituted α-diazo esters
were relatively lower than those derived from para-substituted
α-diazo esters because of steric hindrance (6 vs 8 and 9). Note
that aziridine product 11 bearing a naphthyl ring was also
achieved, albeit with a low yield (33%). Next, the effect of the
ester moiety of α-diazo esters was also investigated. We are
grateful that different alkyl ester (13−16)- or cycloalkyl ester
(17 and 18)-derived α-diazo esters showed good compatibility
to produce the corresponding heterocyclic products in good
yields. In addition, several hexahydro-1,3,5-triazines were
applied as formaldimine precursors in this visible light-
promoted formal [2+1] cycloaddition process. To our delight,
when the aryl rings of hexahydro-1,3,5-triazines bearing
different sensitive functional groups (e.g., halogens, alkyne,
ketone, or ester) were used as surrogates of formaldimines, all
reactions proceeded smoothly and furnished the expected
aziridine products in good yields (19−26).
During the reaction optimization, we were pleased to find
that the reaction media had a significant effect on product
formation. When the solvent was changed from DMSO to
DCM, a formal [4+1] cycloaddition adduct, imidazolidine 27,
was obtained in 74% yield of the isolated product after
irradiation for 12 h (for details of the optimization, see the
Supporting Information). As shown in Scheme 3, incorpo-
a
Scheme 3. Reaction Scope of Imidazolidines
a,b
Scheme 2. Reaction Scope of Aziridines
a
Reaction performed with diazoalkane (0.2 mmol) and 1,3,5-triazine
(0.1 mmol) in DCM (2.0 mL) at rt under 24 W blue LED irradiation.
ration of both electron-rich and electron-deficient substituents
on the phenyl ring of α-diazo esters generally afforded the
corresponding imidazolidine in good yields (28−37). The
relatively low yield of 33 might be due to the steric effect.
More significantly, disubstituted α-diazo esters were also
amenable substrates to afford product 34 in 76% yield. Apart
from phenyl-derived α-diazo esters, methyl 2-diazo-2-(naph-
thalen-2-yl) acetate reacted well with PMP-protected hexahy-
dro-1,3,5-triazine 2a to give 35 in 71% yield. Importantly, the
a
Reaction performed with diazoalkane (0.45 mmol) and 1,3,5-triazine
(0.05 mmol) in DMSO (2.0 mL) at rt under 24 W blue LED
b
c
irradiation for 12 h. Yield of the isolated product. Diazoalkane (0.15
mmol) and 1,3,5-triazine (0.15 mmol). Diazoalkane (0.15 mmol)
and 1,3,5-triazine (0.05 mmol). Twenty-four hours.
d
e
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Letter
reaction was tolerated well with many sensitive functional
groups, such as esters (36 and 37), a carbon−carbon double
bond (42), and a triple bond (43). It was noteworthy that
carbene cyclopropanation or cyclopropenation products were
not observed in the cases of substrates containing unsaturated
double or triple bonds. Then, substituent modification of the
ester group in diazoalkane components was investigated. It was
found that replacement of the methyl group in 1 with other
primary alkyl groups (38), a secondary alkyl group (39), and
cyclic alkyl groups (40 and 41) all proved to be successful,
providing the corresponding imidazolidine heterocycles in
moderate to good yields (51−69%). To our delight, spiro-
imidazolidine 44 could be successfully obtained in moderate
yield through the reaction of cyclic diazo compounds with
1,3,5-triazine 2a under our optimal reaction conditions.
Moreover, different aryl-substituted hexahydro-1,3,5-triazines
were also examined, thus giving the corresponding imidazo-
lidines in good yields (45−48). Note that alkyl-substituted
hexahydro-1,3,5-triazine was not suitable in the current
reaction system (49).
Scheme 5. Mechanistic Studies
react with α-diazo esters 1a in DMSO under standard reaction
conditions (Scheme 5A). After irradiation for 12 h, the desired
aziridine 3 could be obtained in 64% yield, indicating the
formaldimine was formed during the formation of aziridine. In
addition, performing the reaction of aziridine 3 with 2a under
blue LED irradiation in DCM or DMSO resulted in the
formation of only imidazolidine 27 in very low yield [<5%
(Scheme 5B)]. These results indicated that the formation of
imidazolidine 27 through the ring-opening cycloaddition of
aziridine 3 with in situ-generated formaldimine from 1,3,5-
triazine 2a might not be the predominate way. The reactions of
various aryl-substituted 1,3,5-triazines with methyl 2-diazo-2-
phenylacetate 1a under standard reaction conditions were also
examined (Scheme 5C). After irradiation for 12 h,
imidazolidines 27 and 46 were isolated in 69% and 77%
yields, respectively. In contrast, only a trace amount of the
cross-cycloaddition product was detected by LC-MS analysis,
which further excluded the formation of formaldimine from
hexahydro-1,3,5-triazines in the case of the imidazolidine
formation process.
To further explore the potential application of this method
in the pharmaceutical industry, we tested visible light-
promoted selective cycloaddition chemistry on late-stage
modifications of several biologically active molecules. As
shown in Scheme 4, the [2+1] cycloaddition process could
Scheme 4. Bioactive Molecule Analogue Modifications
On the basis of the experimental results presented above and
previous reports, a plausible reaction mechanism is proposed in
Figure S1.11,13 Under visible light irradiation, photolysis of aryl
diazoacetate gives a carbene species (Int-A) with the release of
nitrogen gas. It is well-known that heteroatom nucleophiles can
react with carbene species to generate ylide intermediates.13
To understand the pathways of this divergent heterocycle
formation process, free energy surfaces are calculated by
gradient-corrected density functional theory with dispersion
corrections (M06-2X/cc-pVTZ) in Gaussian 09 (version
E.01).20 As the reaction was performed in DCM, direct
reaction of 1,3,5-triazine with Int-A provides Int-B by ylide
formation with a reaction free energy of −16.81 kcal/mol. Ring
opening of Int-B gives zwitterionic intermediate C via the
cleavage of the C−N bond with a free energy barrier of 7.33
kcal/mol, which subsequently transfers to C′ through
neighboring σ-C−N bond rotation with a very low energy of
isomerization of 0.1 kcal/mol. In chairlike Int-C, the chair
distortion of the triazine ring corresponds to a very low
frequency mode (41 cm−1), suggesting that the innate
flexibility of the ring is an important factor in the deformation
to facilitate the final cyclization. Finally, an intramolecular
substitution of C′ provides imidazolidine 45, together with the
release of formaldimine. The rate-determining step occurs with
connection of the C−C bond (TS2) in forming product 45.
be further applied to the synthesis of aziridines containing
biologically important complex molecules by using L-menthol,
citronellol, L-(−)-borneol, and metronidazole as examples
(50−53, respectively). We also introduced some natural
products or drug-derived complex molecules, such as estrone,
propofol, pterostilbene, gemfibrozil, L-(−)-borneol, citronellol,
and cholesterol, into diazoalkane starting materials. To our
satisfaction, all o fthese α-diazo esters reacted well in DCM
under only blue LED irradiation, affording the corresponding
imidazolidine-modified complex structures in good yields
(54−60, 55−87% yields).
Some control experiments were conducted as shown in
Scheme 5 to better understand the reaction mechanism.
Initially, formaldimine 61 was presynthesized and applied to
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The free energy of 9.61 kcal/mol for this step (at 298 K) is
consistent with the experimental temperature.
AUTHOR INFORMATION
Corresponding Authors
■
To experimentally explain the formation of aziridine, a
formal [2+1] cycloaddition is first proposed in Figure S1b
(path A) with the solvent effect of DMSO. The reaction is
triggered by mixing Int-A and formaldimine (Int-D), where
Int-D is generated by dissolution of 1,3,5-triazine. Then, the
reaction of the nitrogen atom of formaldimine with carbene
species A gives ylide Int-E. The combination of two reactants
with very high reactivity decreases the free energy of −38.54
kcal/mol for the system. The Mulliken charge distribution of
Int-E reveals a substantial polarization of the C1N−C2
bonds [q(C1) = −0.28, and q(C2) = 0.30], indicating the
possibility of the connection of two polarized C atoms.
Therefore, Int-E subsequently undergoes intramolecular
cyclization via TS3 to provide aziridine 19 with a barrier of
only 8.19 kcal/mol. In addition to this [2+1] cycloaddition
mechanism, we also tried to consider an alternative pathway
shown in Figure S1b (path B). With the solvent effect of
DMSO, chairlike Int-C is generated by the ring opening of Int-
B via TS1 (in DMSO) with a barrier of 6.93 kcal/mol, which
might also lead to the formation of aziridines. However, DFT
calculation reveals that the energy barrier reaches 41.9 kcal/
mol upon cyclization to form aziridines 19 with the departure
of two groups of formaldimine. On the basis of natural
population analysis of Int-C (in DMSO), we hypothesize the
electrostatic attraction between the polarized C3N−C4
[q(C3) = −0.08, and q(C4) = −0.36] has difficulty in
triggering the dissociation of the ring. Therefore, the favored
pathway in the formation of aziridine 19 is the [2+1]
cycloaddition shown in path A with a rate-determining free
energy barrier of 8.19 kcal/mol.
In summary, we developed a visible light-promoted
divergent cycloaddition of α-diazo esters with hexahydro-
1,3,5-triazines. Under environmentally benign blue LED
irradiation, series of aziridine and imidazolidine frameworks
could be obtained in good to excellent yields by simply
changing the reaction solvent. In addition, the synthetic value
of this benign protocol was further demonstrated by successful
construction of aziridines and imidazolidines containing
important natural isolates and drug-based complex molecules.
Mechanistic studies based on control experiment results and
DFT calculations revealed that both 1,3,5-triazines and the in
situ formation of formaldimines could serve as carbene
trapping reagents to form key nitrogen ylide intermediates.
Kun Wang − Anhui Province Key Laboratory of Chemistry for
Inorganic/Organic Hybrid Functionalized Materials, College
of Chemistry & Chemical Engineering, Anhui University,
Hefei, Anhui 230601, People’s Republic of China;
orcid.org/0000-0003-2175-1105; Email: wangkun@
ahu.edu.cn
Jun Xuan − Anhui Province Key Laboratory of Chemistry for
Inorganic/Organic Hybrid Functionalized Materials, College
of Chemistry & Chemical Engineering, Anhui University,
Hefei, Anhui 230601, People’s Republic of China; Key
Laboratory of Structure and Functional Regulation of Hybrid
Materials (Anhui University), Ministry of Education, Hefei
230601, People’s Republic of China; Key Laboratory of
Precise Synthesis of Functional Molecules of Zhejiang
Province, School of Science, Westlake University, Hangzhou
310024, Zhejiang, China; orcid.org/0000-0003-0578-
9330; Email: xuanjun@ahu.edu.cn
Authors
Xiao Cheng − Anhui Province Key Laboratory of Chemistry
for Inorganic/Organic Hybrid Functionalized Materials,
College of Chemistry & Chemical Engineering, Anhui
University, Hefei, Anhui 230601, People’s Republic of China
Bao-Gui Cai − Anhui Province Key Laboratory of Chemistry
for Inorganic/Organic Hybrid Functionalized Materials,
College of Chemistry & Chemical Engineering, Anhui
University, Hefei, Anhui 230601, People’s Republic of China
Hui Mao − Anhui Province Key Laboratory of Chemistry for
Inorganic/Organic Hybrid Functionalized Materials, College
of Chemistry & Chemical Engineering, Anhui University,
Hefei, Anhui 230601, People’s Republic of China
Juan Lu − Anhui Province Key Laboratory of Chemistry for
Inorganic/Organic Hybrid Functionalized Materials, College
of Chemistry & Chemical Engineering, Anhui University,
Hefei, Anhui 230601, People’s Republic of China
Lei Li − Anhui Province Key Laboratory of Chemistry for
Inorganic/Organic Hybrid Functionalized Materials, College
of Chemistry & Chemical Engineering, Anhui University,
Hefei, Anhui 230601, People’s Republic of China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c00979
Author Contributions
∥X.C., B.-G.C., and H.M. contributed equally to this work.
ASSOCIATED CONTENT
■
Notes
sı
* Supporting Information
The authors declare no competing financial interest.
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c00979.
ACKNOWLEDGMENTS
■
The authors are grateful to the National Natural Science
Foundation of China (21971001, 21702001, and 21701001)
and the Natural Science Research Project of Anhui Province
(KJ2020ZD04) for their financial support of this work.
1
Experimental procedures, characterization data, and H
and 13C NMR spectra (PDF)
Accession Codes
CCDC 2058385 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
REFERENCES
■
(1) (a) Ismail, F. M. D.; Levitsky, D. O.; Dembitsky, V. M. Aziridine
alkaloids as potential therapeutic agents. Eur. J. Med. Chem. 2009, 44,
3373−3387. (b) Thibodeaux, C. J.; Chang, W.-C.; Liu, H.-W.
Enzymatic chemistry of cyclopropane, epoxide, and aziridine biosyn-
thesis. Chem. Rev. 2012, 112, 1681−1709.
4112
https://doi.org/10.1021/acs.orglett.1c00979
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Organic Letters
pubs.acs.org/OrgLett
Letter
(2) (a) Kametani, T.; Honda, T. Application of aziridines to the
synthesis of natural products. Adv. Heterocycl. Chem. 1986, 39, 181−
236. (c) Rotstein, B. H.; Zaretsky, S.; Rai, V.; Yudin, A. K. Small
heterocycles in multicomponent reactions. Chem. Rev. 2014, 114,
8323−8359.
704−724. (c) Zhu, S.-F.; Zhou, Q.-L. Iron-catalyzed transformations
of diazo compounds. Natl. Sci. Rev. 2014, 1, 580−603. (d) Bauer, I.;
Knolker, H.-J. Iron Catalysis in Organic Synthesis. Chem. Rev. 2015,
115, 3170−3387. (e) Xia, Y.; Qiu, D.; Wang, J. Transition-metal-
catalyzed cross-couplings through carbene migratory insertion. Chem.
Rev. 2017, 117, 13810−13889.
(13) (a) Ciszewski, L. W.; Rybicka-Jasinska, K.; Gryko, D. Recent
developments in photochemical reactions of diazo compounds. Org.
Biomol. Chem. 2019, 17, 432−448. (b) Yang, Z.; Stivanin, M. L.;
Jurberg, I. D.; Koenigs, R. M. Visible light-promoted reactions with
diazo compounds: a mild and practical strategy towards free carbene
intermediates. Chem. Soc. Rev. 2020, 49, 6833−6847.
(14) (a) Jurberg, I.; Davies, H. M. L. Blue light-promoted photolysis
of aryldiazoacetates. Chem. Sci. 2018, 9, 5112−5118. (b) Jana, S.;
Yang, Z.; Li, F.; Empel, C.; Ho, J.; Koenigs, R. M. Photoinduced
proton-transfer reactions for mild O-H functionalization of unreactive
alcohols. Angew. Chem., Int. Ed. 2020, 59, 5562−5566.
(15) (a) Guo, Y.; Nguyen, T. V.; Koenigs, R. M. Norcaradiene
synthesis via visible-light-mediated cyclopropanation reactions of
arenes. Org. Lett. 2019, 21, 8814−8818. (b) Hommelsheim, R.; Guo,
Y.; Yang, Z.; Empel, C.; Koenigs, R. M. Blue-light-induced carbene-
transfer reactions of diazoalkanes. Angew. Chem., Int. Ed. 2019, 58,
1203−1207.
(3) (a) Callebaut, G.; Meiresonne, T.; De Kimpe, N.; Mangelinckx,
S. Synthesis and reactivity of 2-(carboxymethyl)aziridine derivatives.
Chem. Rev. 2014, 114, 7954−8015. (b) Mukherjee, A.; Ghosal, N. C.;
Zyryanov, G. V.; Majee, A.; Santra, S. An updated library on the
synthesis of aziridines. Current Green Chem. 2019, 6, 226−241.
(4) (a) Narayanam, J. M. R.; Stephenson, C. R. J. Visible light
photoredox catalysis: applications in organic synthesis. Chem. Soc. Rev.
2011, 40, 102−113. (b) Prier, C. K.; Rankic, D. A.; MacMillan, D. W.
C. Visible light photoredox catalysis with transition metal complexes:
applications in organic synthesis. Chem. Rev. 2013, 113, 5322−5363.
(c) Marzo, L.; Pagire, S.; Reiser, O.; König, B. Visible-light
photocatalysis: does it make a difference in organic synthesis?
Angew. Chem., Int. Ed. 2018, 57, 10034−10072. (d) Cai, B.-G.; Xuan,
J.; Xiao, W.-J. Visible light-mediated C-P bond formation reactions.
Sci. Bull. 2019, 64, 337−350. (e) Chen, Y.; Lu, L.-Q.; Yu, D.-G.; Zhu,
C.-J.; Xiao, W.-J. Visible light-driven organic photochemical synthesis
in China. Sci. China: Chem. 2019, 62, 24−57. (f) Xuan, J.; He, X.-K.;
Xiao, W.-J. Visible light-promoted ring-opening functionalization of
three-membered carbo- and heterocycles. Chem. Soc. Rev. 2020, 49,
2546−2556.
(16) (a) Yang, J.; Wang, J.; Huang, H.; Qin, G.; Jiang, Y.; Xiao, T.
gem-difluoroallylation of aryl diazoesters via catalyst-free, blue-light-
mediated formal Doyle−Kirmse reaction. Org. Lett. 2019, 21, 2654−
2657. (b) Yang, Z.; Guo, Y.; Koenigs, R. M. Photochemical, metal-
free sigmatropic rearrangement reactions of sulfur ylides. Chem. - Eur.
(5) Kim, E.; Choi, S.; Kim, H.; Cho, E. J. Generation of CF3-
containing epoxides and aziridines by visible-light-driven trifluor-
omethylation of allylic alcohols and amines. Chem. - Eur. J. 2013, 19,
6209−6212.
́
J. 2019, 25, 6703−6706. (c) Orłowska, K.; Rybicka-Jasinska, K.;
(6) (a) Scholz, S. O.; Farney, E. P.; Kim, S.; Bates, D. M.; Yoon, T.
P. Spin-selective generation of triplet nitrenes: olefin aziridination
through visible-light photosensitization of azidoformates. Angew.
Chem., Int. Ed. 2016, 55, 2239−2242. (b) Yu, W.-L.; Chen, J.-Q.;
Wei, Y.-L.; Wang, Z.-Y.; Xu, P.-F. Alkene functionalization for the
stereospecific synthesis of substituted aziridines by visible-light
photoredox catalysis. Chem. Commun. 2018, 54, 1948−1951.
(c) Govaerts, S.; Angelini, L.; Hampton, C.; Malet-Sanz, L.;
Ruffoni, A.; Leonori, D. Photoinduced olefin diamination with
alkylamines. Angew. Chem., Int. Ed. 2020, 59, 15021−15028. (d) Guo,
Y.; Pei, C.; Jana, S.; Koenigs, R. M. Synthesis of trifluoromethylated
aziridines via photocatalytic amination reaction. ACS Catal. 2021, 11,
337−342.
Krajewski, P.; Gryko, D. Photochemical Doyle−Kirmse reaction: a
route to allenes. Org. Lett. 2020, 22, 1018−1021.
(17) (a) Xiao, T.; Mei, M.; He, Y.; Zhou, L. Blue light-promoted
cross-coupling of aryldiazoacetates and diazocarbonyl compounds.
Chem. Commun. 2018, 54, 8865−8868. (b) Wei, Y.; Liu, S.; Li, M.-M.;
Li, Y.; Lan, Y.; Lu, L.-Q.; Xiao, W.-J. Enantioselective trapping of Pd-
containing 1,5-dipoles by photogenerated ketenes: access to 7-
membered lactones bearing chiral quaternary stereocenters. J. Am.
Chem. Soc. 2019, 141, 133−137. (c) da Silva, A. F.; Afonso, M. A. S.;
Cormanich, R. A.; Jurberg, I. D. Room temperature coupling of
aryldiazoacetates with boronic acids enhanced by blue light
irradiation. Chem. - Eur. J. 2020, 26, 5648−5653. (d) Cheng, R.;
Qi, C.; Wang, L.; Xiong, W.; Liu, H.; Jiang, H. Visible light-promoted
synthesis of organic carbamates from carbon dioxide under catalyst-
and additive-free conditions. Green Chem. 2020, 22, 4890−4895.
(e) Cai, B.-G.; Luo, S.-S.; Li, L.; Li, L.; Xuan, J.; Xiao, W.-J. Visible
light-promoted amide bond formation via one-pot nitrone in situ
formation/rearrangement cascade. CCS Chem. 2020, 2, 2764−2771.
(f) Ye, C.; Cai, B.-G.; Lu, J.; Cheng, X.; Li, L.; Pan, Z.-W.; Xuan, J.
Visible-light-promoted polysubstituted olefins synthesis involving
sulfur ylides as carbene trapping reagents. J. Org. Chem. 2021, 86,
1012−1022.
(7) Liu, Y.; Dong, X.; Deng, G.; Zhou, L. Synthesis of aziridines by
visible-light induced decarboxylative cyclization of N-aryl glycines and
diazo compounds. Sci. China: Chem. 2016, 59, 199−202.
(8) Shen, T.; Lambert, T. H. Electrophotocatalytic diamination of
vicinal C−H bonds. Science 2021, 371, 620−626.
(9) Bischoff, C. A.; Reinfeld, F. Formaldehydderivate aromatischer
Basen. Ber. Dtsch. Chem. Ges. 1903, 36, 41−53.
(10) Liang, D.; Xiao, W.-J.; Chen, J.-R. Recent advances of 1,3,5-
triazinanes in aminomethylation and cycloaddition reactions. Synthesis
2020, 52, 2469−2482. and references cited therein
(18) (a) Jana, S.; Yang, Z.; Pei, C.; Xu, X.; Koenigs, R. M.
Photochemical ring expansion reactions: synthesis of tetrahydrofuran
derivatives and mechanism studies. Chem. Sci. 2019, 10, 10129−
10134. (b) Ansari, M. A.; Yadav, D.; Singh, M. S. Visible-light-driven
photocatalyst-and additive-free cross-coupling of β-ketothioamides
with α-diazo 1,3-diketones: access to highly functionalized thiazolines.
Chem. - Eur. J. 2020, 26, 8083−8089. (c) Chen, J.; Liu, S.; Lv, X.;
Hong, K.; Lei, J.; Xu, X.; Hu, W. Blue light-promoted formal [4 + 1]-
annulation of diazoacetates with o-aminoacetophenones: synthesis of
polysubstituted indolines and computational study. J. Org. Chem.
2020, 85, 13920−13928.
(19) (a) Xuan, J.; Studer, A. Radical cascade cyclization of 1,n-
enynes and diynes for the synthesis of carbocycles and heterocycles.
Chem. Soc. Rev. 2017, 46, 4329−4346. (b) Cheng, X.; Cao, X.; Xuan,
J.; Xiao, W.-J. Silver(I)- and base-mediated [3 + 3]-cycloaddition of
C,N-cyclic azomethine imines with aza-oxyallyl cations. Org. Lett.
2018, 20, 52−55. (c) Cao, X.; Cheng, X.; Xuan, J. Arylsulfonyl radical
triggered 1,6-enyne cyclization: synthesis of γ-lactams containing
(11) (a) Ha, H.-J.; Kang, K.-H.; Suh, J.-M.; Ahn, Y.-G. A new
synthesis of aziridine-2-carboxylates by reaction of hexahydro-1,3,5-
triazines with alkyldiazoacetates in the presence of Tin(IV) chloride.
Tetrahedron Lett. 1996, 37, 7069−7070. (b) Ha, H.-J.; Suh, J.-M.;
Kang, K.-H.; Ahn, Y.-G.; Han, O. A new synthesis of aziridine-2-
carboxylates: Reaction of hexahydro-1,3,5-triazines or N-methoxyme-
thylanilines with alkyl diazoacetates in the presence of Lewis acid.
Tetrahedron 1998, 54, 851−858. (c) Zhu, C.-H.; Xu, G.-Y.; Sun, J.-T.
Gold-catalyzed formal [4 + 1]/[4 + 3] cycloadditions of diazo esters
with triazines. Angew. Chem., Int. Ed. 2016, 55, 11867−11871.
(d) Liu, P.; Zhu, C.-H.; Xu, G.-Y.; Sun, J.-T. Iron-catalyzed
intermolecular cycloaddition of diazo surrogates with hexahydro-
1,3,5-triazines. Org. Biomol. Chem. 2017, 15, 7743−7746.
(12) (a) Davies, H. M. L.; Manning, J. R. Catalytic C−H
functionalization by metal carbenoid and nitrenoid insertion. Nature
2008, 451, 417−424. (b) Doyle, M. P.; Duffy, R.; Ratnikov, M.; Zhou,
Z. Catalytic carbene insertion into C−H bonds. Chem. Rev. 2010, 110,
4113
https://doi.org/10.1021/acs.orglett.1c00979
Org. Lett. 2021, 23, 4109−4114

Organic Letters
pubs.acs.org/OrgLett
Letter
alkenyl C−X bonds. Org. Lett. 2018, 20, 449−452. (d) Cai, B.-G.;
Chen, Z.-L.; Xu, G.-Y.; Xuan, J.; Xiao, W.-J. [3 + 2]-cycloaddition of
2H-azirines with nitrosoarenes: visible-light-promoted synthesis of
2,5-dihydro-1,2,4-oxadiazoles. Org. Lett. 2019, 21, 4234−4238.
(e) He, X.-K.; Lu, J.; Zhang, A.-J.; Zhang, Q.-Q.; Xu, G.-Y.; Xuan,
J. BI-OAc-accelerated C3−H alkylation of quinoxalin-2(1H)-ones
under visible-light irradiation. Org. Lett. 2020, 22, 5984−5989.
(20) (a) Zhao, Y.; Truhlar, D. G. The M06 suite of density
functionals for main group thermochemistry, thermochemical
kinetics, noncovalent interactions, excited states, and transition
elements: two new functionals and systematic testing of four M06-
class functionals and 12 other functionals. Theor. Chem. Acc. 2008,
120, 215−241. (b) Dunning, T. H. Gaussian basis sets for use in
correlated molecular calculations. I. The atoms boron through neon
and hydrogen. J. Chem. Phys. 1989, 90, 1007−1023.
4114
https://doi.org/10.1021/acs.orglett.1c00979
Org. Lett. 2021, 23, 4109−4114