Preparation of Heterocycles via Visible-Light-Driven Aerobic Selenation of Olefins with Diselenides

Article abstract of DOI:10.1021/acs.orglett.8b03738

The aerobic dehydrogenative cyclization of alkenes with easily accessible diselenides facilitated by visible light is reported. Notably, the features of this transition-metal-free protocol are pronounced efficiency and practicality, good functional group

Full text of DOI:10.1021/acs.orglett.8b03738

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Preparation of Heterocycles via Visible-Light-Driven Aerobic
Selenation of Olefins with Diselenides
Qing-Bao Zhang,† Pan-Feng Yuan,† Liang-Lin Kai,† Kai Liu,† Yong-Liang Ban,† Xue-Yang Wang,†
Li-Zhu Wu,‡ and Qiang Liu*,†
†State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 South Tianshui Road, Lanzhou 730000, P. R. China
‡Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, the
Chinese Academy of Sciences, Beijing 100190, P. R. China
S
* Supporting Information
ABSTRACT: The aerobic dehydrogenative cyclization of
alkenes with easily accessible diselenides facilitated by visible
light is reported. Notably, the features of this transition-metal-
free protocol are pronounced efficiency and practicality, good
functional group tolerance, atom economy, and high
sustainability, since ambient air and visible light are adequate
for the clean construction of five- and six membered
heterocycles in yields of up to 98%.
rganoselenides, an important class of molecules with
high pharmacological value, are widely found in a great
naturally or biologically active compounds with several
pharmocological properties (e.g., antiobiotic, antitumor, anti-
inflammatory, and antifungal activity, Figure 1).6 Furthermore,
these structures play an important role in asymmetric
synthesis, extensively serving as auxiliaries and ligands.7 For
these reasons, the development of practical and convenient
methods for the construction of oxazolines is highly desirable.
Although there are some approaches to the synthesis of seleno
oxazolines based on a cyclization mode (Scheme 1), these
procedures have certain disadvantages that include the need
for heavy metals and/or heating conditions, the requirement of
excess oxidants, and the generation of equivalents of toxic
byproducts.8
O
number of biologically active compounds and natural products
(Figure 1).1 They also have numerous applications in organic
Scheme 1. Seleno Cyclization of N-Alkenylamides
Figure 1. Examples of biologically active organoselenides and
oxazolines.
synthesis.2 In fact, the seleno group is a very useful and
versatile functionality, because it can be easily removed either
by oxidation or by reduction.3 In recent decades, organo-
selenium-mediated cyclization reactions used in either a
hetero- or carbocyclic ring formation are well documented.4
In particular, the addition of organoselenium cations to
unsaturated compounds has been largely used as a crucial
step in many important synthetic transformations.5 The
transformation is based on the mode of electrophilic
cyclization to produce the corresponding five- or six-
membered heterocycles such as oxazoline, isoxazoline, lactone,
etc. Oxazolines are prevalent units found in a variety of
Received: November 22, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b03738
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Undoubtedly, the employment of diselenides as the
selenylating agent is preferred because diselenides are stable,
easily accessible, and easy to handle during manipulations. In
addition, in a series of independent investigations, both Pandey
et al. and Breder et al. showed that diselenides can be readily
oxidized to generate a PhSe+ intermediate under photo-
chemical conditions in the air.9 Moreover, our group has
reported visible-light-mediated aerobic selenation of (hetero)-
arenes with diselenides through PhSe+ electrophilic addition.10
On the basis of our continuing interest in this field, we design
the seleno functional cyclization of unsaturated compounds by
photoredox catalysis using air as the sole oxidant. To the best
of our knowledge, the use of visible-light catalysis to make
seleno oxazolines through the reaction of olefinic amides with
diselenides has not been reported to date. The method is
considerably more advantageous in terms of green and
sustainable chemistry than the available method because it
(i) is simple to operate and cost-effective, (ii) uses O2 as a
terminal oxidant, and (iii) provides H2O as the primary
byproduct.
nobenzene (4CzIPN) was found to provide the best result,
offering selenation product 3a in 94% yield (entry 10).
Moreover, the absence of light irradiation completely
quenched the reaction, proving that a light mediated reaction
was involved (entry 11).
With the optimized cyclization reaction conditions in hand,
we examined the scope by first varying the allylic amides
(Scheme 2). Various unsaturated amides were competent
a b
,
Scheme 2. Scope of Cyclization of N-Alkenylamides
We commenced our study by using N-allyl-1-naphthamide
(1a) and diphenyl diselenide (2a) as the model substrates for
optimizing the reaction conditions, and the results are shown
in Table 1. The selenative intramolecular cyclization of 1a with
a
Table 1. Optimization of Reaction Conditions
b
entry
catalyst
solvent
time (h)
yield (%)
1
2
3
4
5
6
7
8
9
−
−
−
−
acetone
THF
DCE
24
24
24
24
24
14
10
11
2
19
22
50
73
62
76
81
85
90
94
0
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
a
Reaction conditions: 1 (0.1 mmol), 2a (0.06 mmol), and 4CzIPN (2
Riboflavin
Eosin Y
FIrPic
Fluorescein
Acr-Mes+
4-CzIPN
4-CzIPN
mol %) in CH3CN (2.0 mL) were irradiated with 3 W blue LEDs in
b
air at rt. The reaction was monitored by TLC. Isolated yield.
electrophilic addition partners: N-allylamides 1 with electron-
donating substituents, such as 1-naphthyl, phenyl, 4-methyl
and 4-methoxy groups, performed well with diphenyl
diselenide (2a), affording the desired seleno oxazoline
products 3aa, 3ca−3ea with 85−94% yields. 1,1-Disubstituted
alkene 1b was subjected to the reaction conditions and gave
methyl derivative 3ba in 97% yield. Synthetically attractive
groups (F, Cl, Br, CF3) in substrates 1 were also tolerated in
this reaction providing the products 3fa−3ia in high to
excellent yields. The reaction of heteroaryl substituted amides
proceeded smoothly to afford the corresponding products 3ja
and 3ka in 90% and 44% yields, respectively. Surprisingly,
benzyl substituted amides 1l furnished oxo-oxazoline 3la with a
53% yield.
Next, a diverse array of substituted diselenides were
employed as substrates to explore the scope of this reaction
(Scheme 3). Different electron-donating groups (Me, OMe) or
1-naphthyl (2b, 2c, 2g, 2h) were tolerated with very limited
influence on the yields (71%−80% yields), whereas 1,2-
bis(3,4,5-trimethoxyphenyl) diselane gave the product (3ae) in
moderate yield. Furthermore, steric effects did not significantly
affect the reaction, and on using ortho-substituted diselenides
the corresponding products (3ad, 3af) were obtained in 75%
10
11
4
24
c
a
Reaction conditions: (R1 = naphthalene-1-yl), 1a (0.1 mmol), 2a
(0.06 mmol), catalyst (2 mol %), solvent (2 mL), in air at room
temperature, irradiated by 3 W blue LEDs. The reaction was
monitored by TLC. Isolated yield. Reaction was carried out in the
dark.
b
c
2a was studied in the absence of a photocatalyst under blue
LEDs irradiation using air as the oxidant to form oxazoline 3a
(entries 1−4). After investigating the effect of the solvent on
this cyclization, CH3CN was found to be the best solvent
(entry 4); poor yields (19−50%) of 3a were obtained when
acetone, THF, and DCE were used as the solvent (entries 1−
3). For further optimization, various photoredox catalysts were
examined (entries 5−10). We were delighted to obtain the
desired product 3a in 90% yield of isolated product, when
using 2 mol % of 9-mesityl-10-methylacridinium perchlorate
(Mes-Acr+) as the photocatalyst (entry 9), presumably owing
to the high oxidative power of Mes-Acr+ (E*red = 2.06 V vs
SCE) compared to that of other catalysts.11 Notably, the
organo photocatalyst 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicya-
B
DOI: 10.1021/acs.orglett.8b03738
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a b
,
enoate and 2-allylphenol were efficient substrates and afforded
products (5ca, 5ea) in 71% and 98% yields. The selenocycliza-
tion of enol resulted in 84% and 85% yields of seleno
tetrahydrofuran (5da) and a tetrahydro-2H-pyran derivative
(5fa). Using the alkenoic acids as substrates, we observed the
construction of five- and six-membered lactone rings (5ga−
5la) in moderate to excellent yields. Notably, 5ha was isolated
as an ∼1:1 mixture of diastereomers in 91% combined yield.
The similar diselenide-mediated aerobic intramolecular cycli-
zations of alkenoic acids and alcohols have been disclosed by
Breder and co-workers.12 In all these cases, however, seleno-
free heterocycles were produced instead of seleno-containing
structures.
Scheme 3. Scope of the Reaction of Diselenides
To demonstrate the utility of this visible-light-mediated
protocol, we conducted the reaction between 1i (5 mmol, 1.15
g) and 2a (3 mmol, 0.94 g) in the presence of 4CzIPN (0.5
mol %) on a gram scale (Scheme 5). To our delight, the
Scheme 5. Gram-Scale Seleno Cyclization of 1i and
Derivatization of Oxazoline 3ia
a
Reaction conditions: (R1 = naphthalene-1-yl) 1a (0.1 mmol), 2
(0.06 mmol), and 4CzIPN (2 mol %) in CH3CN (2.0 mL) were
irradiated with 3 W blue LEDs in air at rt. The reaction was
b
monitored by TLC. Isolated yield.
and 70% yields, respectively. Importantly, the dialkyl
diselenides were good reaction partners and provided oxazo-
line (3ai, 3aj) in good yields.
Encouraged by our results with allylic amides, we shifted our
focus to investigate the scope of the nucleopilic reagent
(Scheme 4). As we expected, formation of Ts-protected
pyrrolidine 5aa proceeded in 98% yield while isoxazoline 5ba
was formed in a moderate 67% yield. Ethyl 2-benzoylpent-4-
corresponding product 3ia was obtained in 80% isolated yield
with a prolonged time. Furthermore, functional group
transformations of 3ia were also pursued. Treatment of
selenide 3ia with H2O2 lead to the formation of selenoxides
6a in 89% yield. Besides, the oxazoline moiety of 3ia could also
be easily hydrolyzed at room temperature, delivering vicinal
amino alcohol 6b in high yield.
The photoluminescence of 4CzIPN was quenched by
diphenyl diselenide (2a) with a rate constant of 6.03 × 102
L·mol−1. In contrast, the quenching rate constant of 4CzIPN
with N-allyl-1-naphthamide (1a) was much smaller (1.16 ×
102 L·mol−1) (see SI, Figure S3). This result indicated that the
photoreaction may be mainly initiated by the interaction
between the excited 4CzIPN and diselenide. The oxidation
potential of diphenyl diselenide 2a is 1.35 V (vs SCE),13 and
the reduction potential of the excited 4CzIPN is 1.35 V (vs
SCE).14 Thus, the electron transfer from 2a to the excited
4CzIPN is thermodynamically feasible for seleno intra-
molecular cyclization.
Scheme 4. Scope of Cyclization of Unsaturated
a b
,
Compounds
On the basis of our observations and literature reports,12a,15
a plausible mechanism is proposed in Scheme 6. Under visible-
light irradiation, 4CzIPN is converted to the excited 4CzIPN*.
A single electron transfer between diphenyl diselenide 2a and
4CzIPN* affords the 2a•+ radical cation and generates the
4CzIPN•− radical anion. The photoredox cycle is completed
by the molecular oxygen oxidation of 4CzIPN•− to the ground
state. Subsequent reaction of diselane radical cation 2a•+ with
N-alkenylamide 1c produces seleniranium cation A and 0.5
equiv of diphenyl diselenide 2a.16 Finally, the desired product
3c is generated via intramolecular nucleophilic cyclization of
intermidate A.
a
Reaction conditions: 4 (0.1 mmol), 2a (0.06 mmol), and 4CzIPN (2
mol %) in CH3CN (2.0 mL) were irradiated with 3 W blue LEDs in
air at rt. The reaction was monitored by TLC. Isolated yield.
b
C
DOI: 10.1021/acs.orglett.8b03738
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
1636. (e) Yu, J.-M.; Cai, C. Org. Biomol. Chem. 2018, 16, 490−498.
(f) Chen, Y.; Cho, C. H.; Larock, R. C. Org. Lett. 2009, 11, 173−176.
(g) Gay, R. M.; Manarin, F.; Caroline, C.; Schneider, C. C.;
Barancelli, D. A.; Costa, M. D.; Zeni, G. J. Org. Chem. 2010, 75,
5701−5706. (h) Mitamura, T.; Iwata, K.; Nomoto, A.; Ogawa, A. Org.
Biomol. Chem. 2011, 9, 3768−3775.
Scheme 6. Postulated Cyclization Reaction Mechanism
(3) (a) Pandey, G.; Sekhar, B. B. V.S.; Bhalerao, U. T. J. Am. Chem.
Soc. 1990, 112, 5650−5651. (b) Pandey, G.; Tiwari, S. K.; Singh, B.;
Vanka, K.; Jain, S. Chem. Commun. 2017, 53, 12337−12340.
(c) Barton, D. H. R.; Csiba, M. A.; Jaszberenyi, J. C. Tetrahedron
Lett. 1994, 35, 2869−2872. (d) Spell, M.; Wang, X. P.; Wahba, A. E.;
Conner, E.; Ragains, J. Carbohydr. Res. 2013, 369, 42−47.
(4) (a) Tsuchii, K.; Doi, M.; Hirao, T.; Ogawa, A. Angew. Chem., Int.
Ed. 2003, 42, 3490−3493. (b) Sahoo, H.; Mandal, A.; Dana, S.;
Baidya, M. Adv. Synth. Catal. 2018, 360, 1099−1103. (c) Stein, A. L.;
Bilheri, F. N.; Back, D. F.; Zeni, G. Adv. Synth. Catal. 2014, 356, 501−
508.
(5) (a) Pandey, G.; Gadre, S. R. Acc. Chem. Res. 2004, 37, 201−210.
(b) Conner, E. S.; Crocker, K. E.; Fernando, R. G.; Fronczek, F. R.;
Stanley, G. G.; Ragains, J. R. Org. Lett. 2013, 15, 5558−5561.
(c) Nicolaou, K. C.; Magolda, R. L.; Sipio, W. J.; Barnette, W. E.;
Lysenko, Z.; Joullie, M. J. Am. Chem. Soc. 1980, 102, 3784−3793.
(d) Nicolaou, K. C. Tetrahedron 1981, 37, 4097−4109. (e) Kon-
In conclusion, we have developed an economical and highly
efficient methodology for the synthesis of heterocycles through
selenation of alkenes with diselenides using molecular oxygen
as a terminal oxidant under visible-light irradiation. Various
aryl/alkyl diselenides and alkenes were suitable for this
transformation and afforded heterocycles (such as oxazoline,
isoxazoline, pyrrolidine, lactone, etc.) in excellent yields.
Notably, the products can be used as direct precursors to
construct an array of important molecules.
́
́
́
́
stantinovic, S.; Vukicevic, R.; Mihailovic, M. L. Tetrahedron Lett.
̌
́
́
1987, 28, 6511−6512. (f) Bugarcic, Z. M.; Mojsilovic, B. M.; Vera,
M.; Divac, V. M. J. Mol. Catal. A: Chem. 2007, 272, 288−292. (g) Shi,
H. W.; Yu, C.; Zhu, M.; Yan, J. Synthesis 2015, 48, 57−64. (h) Tiecco,
M.; Testaferri, L.; Temperini, A.; Bagnoli, L.; Marini, F.; Santi, C.
Synlett 2001, 2001, 1767−1771. (i) Tingoli, M.; Diana, R.; Panunzi,
B. Tetrahedron Lett. 2006, 47, 7529−7537.
ASSOCIATED CONTENT
* Supporting Information
■
S
(6) (a) Onishi, H. R.; Pelak, B. A.; Lynn, S.; Gerckens, L. S.; Silver,
L. L.; Kahan, F. M.; Chen, M.-H.; Patchett, A. A.; Galloway, S. M.;
Hyland, S. A.; Anderson, M. S.; Raetz, C. R. H. Science 1996, 274,
980−982. (b) Li, Q.; Woods, K. W.; Claiborne, A.; Gwaltney, S. L., II;
Barr, K. J.; Liu, G.; Gehrke, L.; Credo, R. B.; Hui, Y. H.; Lee, J.;
Warner, R. B.; Kovar, P.; Nukkala, M. A.; Zielinski, N. A.; Tahir, S. K.;
Fitzgerald, M.; Kim, K. H.; Marsh, K.; Frost, D.; Ng, S. C.; Rosenberg,
S.; Sham, H. L. Bioorg. Med. Chem. Lett. 2002, 12, 465−469. (c) Faizi,
S.; Farooqi, F.; Zikr-Ur-Rehman, S.; Naz, A.; Noor, F.; Ansari, F.;
Ahmad, A.; Khan, S. A. Tetrahedron 2009, 65, 998−1004.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b03738.
Detailed experimental procedures, mechanism studies,
and full spectroscopic data for all new compounds
(PDF)
AUTHOR INFORMATION
■
(7) (a) McManus, H. A.; Guiry, P. J. Chem. Rev. 2004, 104, 4151−
4202. (b) Desimoni, G.; Faita, G.; Jørgensen, K. A. Chem. Rev. 2006,
106, 3561−3651. (c) Hargaden, G. C.; Guiry, P. J. Chem. Rev. 2009,
109, 2505−2550.
Corresponding Author
*E-mail: liuqiang@lzu.edu.cn.
ORCID
́
(8) (a) Chretien, F.; Chapleur, Y. J. Org. Chem. 1988, 53, 3615−
Li-Zhu Wu: 0000-0002-5561-9922
Qiang Liu: 0000-0001-8845-1874
Notes
3617. (b) Tiecco, M.; Testaferri, L.; Tingoli, M.; Bartoli, D.; Balducci,
R. J. Org. Chem. 1990, 55, 429−434. (c) Engman, L. J. Org. Chem.
1991, 56, 3425−3430. (d) Tingoli, M.; Tiecco, M.; Testaferri, L.;
Temperini, A. Synth. Commun. 1998, 28, 1769−1778. (e) Berkowitz,
D. B.; McFadden, J. M.; Chisowa, E.; Semerad, C. L. J. Am. Chem. Soc.
2000, 122, 11031−11032.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(9) (a) Pandey, G.; Rao, V. J.; Bhalerao, U. T. J. Chem. Soc., Chem.
Commun. 1989, 416−417. (b) Ortgies, S.; Depken, C.; Breder, A. Org.
We are grateful for financial support from the NSFC (Nos.
21572090 and 21871123) and the Fundamental Research
Funds for the Central Universities (lzujbky-2017-k05).
̈
Lett. 2016, 18, 2856−2859. (c) Depken, C.; Kratzschmar, F.; Rieger,
R.; Rode, K.; Breder, A. Angew. Chem., Int. Ed. 2018, 57, 2459−2463.
(10) Zhang, Q.-B.; Ban, Y.-L.; Yuan, P. − F.; Peng, S.-J.; Fang, J.-G.;
Wu, L.-Z.; Liu, Q. Green Chem. 2017, 19, 5559−5563.
(11) (a) Hamilton, D. S.; Nicewicz, D. A. J. Am. Chem. Soc. 2012,
134, 18577−18580. (b) Fukuzumi, S.; Kotani, H.; Ohkubo, K.; Ogo,
S.; Tkachenko, N. V.; Lemmetyinen, H. J. Am. Chem. Soc. 2004, 126,
1600−1601.
REFERENCES
■
(1) (a) Nogueira, C. W.; Zeni, G.; Rocha, J. B. T. Chem. Rev. 2004,
104, 6255−6285. (b) Mugesh, G.; du Mont, W.-W.; Sies, H. Chem.
Rev. 2001, 101, 2125−2180. (c) Sancineto, L.; Mariotti, A.; Bagnoli,
L.; Marini, F.; Desantis, J.; Iraci, N.; Santi, C.; Pannecouque, C.;
Tabarrini, O. J. Med. Chem. 2015, 58, 9601−9614. (d) Sahu, P. K.;
Umme, T.; Yu, J.; Nayak, K.; Kim, G.; Noh, M.; Lee, J.-Y.; Kim, D.-
D.; Jeong, L. S. J. Med. Chem. 2015, 58, 8734−8738.
(12) (a) Ortgies, S.; Rieger, R.; Rode, K.; Koszinowski, K.; Kind, J.;
Thiele, C. M.; Rehbein, J.; Breder, A. ACS Catal. 2017, 7, 7578−7586.
(b) Rode, K.; Palomba, M.; Ortgies, S.; Rieger, R.; Breder, A. Synthesis
2018, 50, 3875−3885.
(13) Kunai, A.; Harada, J.; Izumi, J.; Tachihara, H.; Sasaki, K.
Electrochim. Acta 1983, 28, 1361−1366.
(14) (a) Uoyama, H.; Goushi, K.; Shizu, K.; Nomura, H.; Adachi, C.
Nature 2012, 492, 234−240. (b) Luo, J.; Zhang, J. ACS Catal. 2016,
(2) (a) Mugesh, G.; Singh, H. B. Chem. Soc. Rev. 2000, 29, 347−357.
̃
(b) Perin, G.; Lenardao, E. J.; Jacob, R. G.; Panatieri, R. B. Chem. Rev.
2009, 109, 1277−1301. (c) Mukherjee, A. J.; Sanjio, S.; Zade, S. S.;
Singh, H. B.; Sunoj, R. B. Chem. Rev. 2010, 110, 4357−4416.
(d) Beletskaya, I. P.; Ananikov, V. P. Chem. Rev. 2011, 111, 1596−
D
DOI: 10.1021/acs.orglett.8b03738
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
6, 873−877. (c) Lu, J.; Pattengale, B.; Liu, Q.; Yang, S.; Shi, W.; Li, S.;
Huang, J.; Zhang, J. J. Am. Chem. Soc. 2018, 140, 13719−13725.
(15) (a) Wilken, M.; Ortgies, S.; Breder, A.; Siewert, I. ACS Catal.
2018, 8, 10901−10912. (b) Minakata, S.; Morino, Y.; Oderaotoshi,
Y.; Komatsu, M. Org. Lett. 2006, 8, 3335−3337. (c) Alhalib, A.;
Kamouka, S.; Moran, W. J. Org. Lett. 2015, 17, 1453−1456.
(d) Nagaraju, K.; Rajesh, N.; Krishna, P. R. Synth. Commun. 2018,
48, 1001−1007. (e) Liu, G. − Q.; Yang, C. − H.; Li, Y. − M. J. Org.
Chem. 2015, 80, 11339−11350. (f) Vieira, A. A.; Azeredo, J. B.;
́
Godoi, M.; Santi, C.; Junior, E. N. S.; Braga, A. L. J. Org. Chem. 2015,
80, 2120−2127.
(16) The detailed procedure for the reaction of diselane radical
cation 2a•+ with N-alkenylamides 1c is still unclear at this point.
Diselane radical cation 2a•+ may undergo heterolytic cleavage of the
Se−Se bond to generate the cation [PhSe]+ and the radical [PhSe·] or
dimerize to a tetrameric dication [(PhSe)4]2+. Both [PhSe]+ and
[(PhSe)4]2+ are efficient selenium-π-acid intermediates, which could
be trapped by N-alkenylamide 1c. For a detailed kinetic and
thermodynamic analysis of the diselenide mediated anodic cyclizaion,
please see ref 15a.
E
DOI: 10.1021/acs.orglett.8b03738
Org. Lett. XXXX, XXX, XXX−XXX