Selenium-π-Acid Catalyzed Oxidative Functionalization of Alkynes: Facile Access to Ynones and Multisubstituted Oxazoles

Article abstract of DOI:10.1021/acscatal.8b01595

Unprecedented selenium-catalyzed propargylic oxidation of alkynes is disclosed. Various propargylphosphonates and 3-alkynoates were efficiently converted to valuable ynones via unusual C-C triple bond migration and deselenenylation at a vinyl carbon. By the strategies of tautomerization of enamine intermediate and S_N2 displacement, similar conditions were effective for the oxidative difunctionalization of ynamides to afford multisubstituted oxazoles with high regioselectivity. Mechanistic studies revealed these detailed processes.

Full text of DOI:10.1021/acscatal.8b01595

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Letter
Selenium-#-Acid Catalyzed Oxidative Functionalization of
Alkynes: Facile Access to Ynones and Multisubstituted Oxazoles
Lihao Liao, Hang Zhang, and Xiaodan Zhao
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b01595 • Publication Date (Web): 19 Jun 2018
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ACS Catalysis
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Selenium-π-Acid Catalyzed Oxidative Functionalization of Al-
kynes: Facile Access to Ynones and Multisubstituted Oxa-
zoles
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Lihao Liao, Hang Zhang, and Xiaodan Zhao*
Institute of Organic Chemistry & MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun
Yat-Sen University, Guangzhou 510275, P. R. China
Supporting Information Placeholder
ABSTRACT: Unprecedented selenium-catalyzed propargylic oxidation of alkynes is disclosed. Various propargylphosphonates
and 3-alkynoates were efficiently converted to valuable ynones via unusual C–C triple bond migration and deselenenylation at a
vinyl carbon. By the strategies of tautomerization of enamine intermediate and SN2 displacement, the similar conditions were effec-
tive for the oxidative difunctionalization of ynamides to afford multisubstituted oxazoles with high regioselectivity. Mechanistic
studies revealed these detailed processes.
KEYWORDS: selenium catalysis, π-activation, alkyne, propargylic oxidation, difunctionalization
Alkynes are useful building blocks in organic synthesis owing
to the versatile reactivities of C–C triple bonds.1 They can be
converted to a variety of compounds by the powerful strategy
of catalytic π-activation.2-5 In the past decades, alkyne π-
activation has been dominated by metal catalysis.2 Recently,
the activation by organocatalysts such as Brønsted acids,3 or-
ganoborons,4 and organoiodides,5 has been paid much atten-
tion since organocatalysis might enable new reactions.6 De-
spite these efforts, approaches for organocatalytic challenging
alkyne transformations are still limited. Thus, developing new
methods of organocatalytic alkyne π-activation to meet the
requirement of synthetic diversity is highly desirable.
Organoselenium catalysis has emerged as a powerful tool
for the synthesis of various compounds.7-11 As an important
part in this field, selenium-π-acid catalysis through electro-
philic interactions between selenenium and π bond is different
with peroxyseleninic acid catalysis probably through oxygen
transfer to π bond.7a,7b,7f This catalysis has garnered considera-
ble attention in recent years since selenium-π-acid exhibits a
distinct carbophilicity to alkene π bond.8a As a result, catalytic
oxidative functionalization of alkenes has been well estab-
lished.9,10 Generally, this transformation goes through nucleo-
Scheme 1. Selenium-π-Acid Catalyzed Transformations of
Alkenes and Alkynes
philic ring opening of seleniranium intermediate and then oxi-
dation of alkyl selenium species followed by syn-H elimina-
tion or SN2 displacement (Scheme 1a, top). Alkynes have
Restricting the development of this area might be ascribed
similar π bonds to alkenes, which implies the potentiality of
to two issues: (i) vinyl cation, a resonance structure of sele-
oxidative transformation by selenium-π-acid catalysis. How-
nirenium, is much less stable than a secondary carbocation
ever, selenium-π-acid catalyzed reactions of alkynes were
from seleniranium resulting in a limited range of nucleo-
considered to be challenging. Until now, only catalytic oxida-
philes;12 (ii) deselenenylation of vinyl selenium species re-
tion of alkynes to form protected and unprotected 1,2-
quires harsh oxidative conditions in which substrates and
diketones has been reported.11 Important reactions such as
products could not tolerate to lead to more side reactions.12a,13
selenium-π-acid catalyzed propargylic functionalization and
difunctionalization of alkynes have not been developed
(Scheme 1a, bottom).
As our continuous interest in chalcogenide catalysis,14 espe-
cially selenium-π-acid catalysis,10 we would like to solve these
issues by new strategies to pave a route for oxidative function-
alization of alkynes. We hypothesized that the limited range of
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nucleophiles resulted from the less stability of vinyl cation
Page 2 of 7
bulky N–F oxidant [TMPy][OTf] in the presence of PhSeSePh
(10 mol%) at room temperature. H2O was used as nucleophile
to generate propargylic alcohol as expected product. Instead, a
propargylic oxidation product 2a was formed via triple bond
migration and further oxidation of hydroxy group (entry 1).
Although the yield was only 5%, this result reflected that dese-
lenenylation of vinyl selenide could occur and propargylic
functionalization was possible. To accelerate deselenenylation
of intermediate, reaction temperature was elevated. When the
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could be handled by using an intramolecular nucleophile to
reduce the energy barrier or a heteroatom-substituted substrate
to stabilize vinyl cation via p-π conjugation. Since N–F type
oxidants were effective in mild deselenenylation of alkyl sele-
nium species with good compatibility,8b it might be suitable
for deselenenylation of vinyl selenium species, which is the
most challenging step for alkyne functionalizations. By using
N–F/diselenide system, we rationalized that challenging pro-
pargylic functionalization and difunctionalization of alkynes
were feasible based on the diverse conversion of vinyl seleni-
um intermediate in Scheme 1b. If R2 on vinyl selenium inter-
mediate I is an electron-withdrawing group, tautomerization
becomes easier to give II. At the same time, the acidity of the
vinyl proton increases, which could benefit the following β-H
elimination to give the final product III (Scheme 1b, left).
Furthermore, we envisioned that when I is an enamine, tau-
tomerization occurs to generate alkyl selenium species IV.
The following oxidative deselenenylation at the sp3 carbon by
SN2 displacement is easier. Then, a second tautomerization
forms C–C double bond to give a difunctionalization product
V (Scheme 1b, right). Herein, we report our discovery that
propargylphosphonates and 3-alkynoates could undergo un-
precedented propargylic oxidation to afford ynones by seleni-
um-π-acid catalysis (Scheme 1c, left). The similar conditions
was effective for oxidative N,O-difunctionalization of yna-
mides to give oxazoles (Scheme 1c, right).
o
reaction was carried out at 80 C, 2a was obtained in 65%
9
yield (entry 3). Other oxidants were tested for the reaction
(entries 4-8). [PyF][OTf] gave slightly better yield (entry 5)
and NFSI led to moderate yield (entry 6). In both reactions,
competitive byproducts that could be possibly formed by the
addition of endogenous nitrogen nucleophiles to substrates
were not observed.9b,10d Next, different solvents were tested
(entries 9 and 10). DCE was found to be slightly more effec-
tive than MeCN and EtOAc, and led to 70% isolated yield of
2a (entry 10). When water or ethanol was utilized as the sol-
vent, ynone product was not observed and most of starting
material remained after the reaction. Other catalyst precursors
of diselenides were evaluated. None of them gave better re-
sults than (PhSe)2 (entries 11-13). The reaction did not work in
the absence of diselenides (entry 14). It is noteworthy that
there are rare methods available for the synthesis of phospho-
nate-substituted ynones.16 Our method is a significant supple-
ment.
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Table 1. Condition Evaluationa
Table 2. Substrate Scope for Propargylic Oxidationa
temp. (oC)
RT
45
solvent
yield (%)b
entry
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2
3
4
5
6
7
8
R
oxidant
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
[TMPy][OTf] MeCN
[TMPy][OTf] MeCN
[TMPy][OTf] MeCN
[TMPy][BF4] MeCN
5
21
65
61
69
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69
72 (70)
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0
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80
80
[Py][OTf]
NFSI
MeCN
MeCN
MeCN
MeCN
EtOAc
DCE
DCE
DCE
DCE
DCE
Selectfluor
PhI(TFA)2
[Py][OTf]
[Py][OTf]
[Py][OTf]
[Py][OTf]
[Py][OTf]
[Py][OTf]
9
10
11 p-MeOC6H4
12 p-CF3C6H4
13
Bn
-
14c
aConditions: 1 (0.15 mmol), (PhSe)2 (10 mol%), [PyF][OTf] (2.2
aConditions: 1a (0.05 mmol), (RSe)2 (10 mol%), oxidant (2.2
equiv), solvent (2 mL), H2O (2.0 equiv), temp., 12 h. Refers to
o
equiv), DCE (6 mL), H2O (2.0 equiv), 80 C, 12 h. For the reac-
b
tions of 3-alkynoates, 1 (0.10 mmol) and [TMPyF][OTf] (2.2
equiv) were used.
NMR yield with BzOBn as the internal standard; isolated yield is
in parentheses in 0.15 mmol scale. cNo (RSe)2.
With the optimal conditions in hand, the scope of propar-
gylphosphonates was evaluated (Table 2). Different dialkyl 3-
phenylpropargylphosphonates efficiently underwent oxidative
migration to afford ynones 2b-d in good yields. Substituents
such as Me–, F–, Cl–, Br–, CF3–, and MeO2C– at the para-,
meta- or ortho-position of the phenyl group did not have a big
impact on this transformation. The corresponding aryl-
substituted ynones were obtained in good yields (2e-l, 60-
Based on our assumption, placing phosphonate group, a
class of important functional groups,15 at the propargylic posi-
tion of substrate could benefit tautomerization and dese-
lenenylation to afford propargylic functionalization product.
So we began our study with easily prepared diethyl (3-phenyl-
2-propynyl)phosphonate (1a) as the model substrate using a
N–F/diselenide system (Table 1). First, 1a was treated with
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74%). 3-Alkylpropargylphosphonates including 1o bearing a
fluor as the oxidant at room temperature (Table 3). It is well-
known that oxazoles are privileged scaffolds in natural prod-
ucts and bioactive molecules.17 Although cycloaddition of
alkynes is a facile method to form oxazoles,18,19 the known
multicomponent cycloaddition of ynamides to substituted oxa-
zoles suffered from limited substrate scope.18f In comparison,
the scope of our reaction is relatively broad. In the reactions, a
series of protecting groups, i.e., Ms–, PhSO2–, Ts–, Ns–, and
carbamate, on the nitrogen atom were well tolerated (4a-e, 80-
94%). Ynimides and ynamines underwent the similar cycload-
dition to give the products nicely (4f-h, 55-79%). When N-aryl
and -alkyl ynamides even bearing a double bond or another
triple bond that could be reactive in selenium catalysis were
used, the reactions worked efficiently without the influence of
the functional groups except that the reaction of TBDMS-
protected ynamide 3o gave the deprotecting product 4o (4i-o,
68-94%). The effect of various substituents on the triple bonds
was studied. It was found that electron-rich and -deficient aryl,
heteroaryl, styryl, and functionalized alkyl groups were well
tolerated (4p-u, 82-96%). It is noted that when terminal yna-
mide substrate was used, the reaction still worked well to give
regioisomer oxazoles (4v+4v', 45%, 6.5:1). When butyroni-
trile was used as solvent, the desired product could be ob-
tained. In addition, the conditions were effective for the syn-
thesis of oxazoles in an intramolecular way. When N-
propargylamides 5 were utilized, cyclization gave oxazole
aldehydes 5a-c in excellent yields (eq. 1).
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7
8
bulky tert-butyl group also underwent the same migration to
form ynones 2m-o in moderate yields. In comparison with aryl
alkyne substrates, alkyl alkynes with less reactivities gave the
products in lower yields. Although the yields are moderate,
these results indicate the generality of this method. To the best
of our knowledge, this work is the first example of catalytic
conversion of sp3 C–P to sp C–P bond. Besides, 3-alkynoates
could also be transformed to the corresponding ester-
substituted ynones under the similar conditions (2p-w, 41-
85%). Similarly, the reactions worked better with aryl-
substituted substrates (1p-1t) than alkyl-substituted those (1u-
1w).
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Table 3. Substrate Scope for N,O-Difunctionalizationa
Scheme 2. Further Transformations of Ynone 2a
aConditions: 3 (0.10 mmol), (PhSe)2 (10 mol%), Selectfluor (1.2
b
equiv), H2O (1.0 equiv), R3CN (8 mL), RT, 12 h. [PyF][OTf]
The obtained phosphonate ynones are good precursors for
the synthesis of valuable heteroaryl phosphonates. For exam-
ple, ynone 2a could be easily converted into polysubstituted
pyridines, pyrimidines and pyrazoles via condensation reac-
tions (Scheme 2, 7a-d). When it was treated with BnN3 or 1-
aminopyridinium iodide, the direct cycloaddition products,
triazole 7e and pyrazolo[1,5-a]pyridine 7f, respectively, were
efficiently formed in excellent regioselectivity.
To elucidate the reaction mechanisms, control experiments
have been conducted. When 1a was treated with 50 mol% of
(PhSe)2 in the presence of different amount of [PyF][OTf] at
different temperature, a selenenylated intermediate 8 with
single configuration was formed, and its yield relied on the
amount of [PyF][OTf] and was slightly affected by tempera-
ture (eq. 2). The more the oxidant was added, the more 8 was
formed. Intermediate 8 could be deselenenylated to give ynone
2a by oxidation (eq. 3). Elevating temperature favored the
(1.2 equiv) was used as the oxidant; MeCN (4 mL). cTBDMS
protected alcohol was utilized as the substrate. dRegioisomers
were formed.
To stabilize vinyl cation from selenirenium and promote
tautomerization of enamine intermediate, ynamides were se-
lected as substrates and acetonitrile was used as nucleophile
and nitrogen source. To our delight, a formal difunctionaliza-
tion product, polysubstituted oxazoles, was formed by this
selenium-π-acid catalysis. The reactions could run with Select-
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deselenenylation process, which is consistent with the results
SN2 displacement is superior to the competitive β-H elimina-
tion in all the reactions of alkyl ynamides.
o
that higher yields were attained at 80 C in Table 1. The 18O
1
labeling experiments were also conducted. The reaction of 1a
with H218O gave 18O labeled pyrimidines, which indicates that
the 18O from H218O was transferred to the phosphonate group,
not triple bond motif (eq. 4). This process offers a good route
for the synthesis of aromatic compounds bearing an 18O-
labeled phosphonate group. Similarly, a selenenylated inter-
mediate 9 was formed when ynamide 3d was treated with 50
mol% of (PhSe)2 and Selectfluor. As expected, oxazole 4d was
formed in high yield through the deselenenylation of 9 with
equimolar Selectfluor. When H218O was used, 18O labeled
oxazole was generated, which indicates that the oxygen on
oxazole comes from H2O.
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Scheme 3. Proposed Mechanism
In summary, we have developed an efficient method for se-
lenium-π-acid catalyzed synthesis of ynones with pro-
parylphosphonates and 3-alkynoates via oxidative triple bond
migration. The similar conditions could be applied to the syn-
thesis of multisubstituted oxazoles by an oxidative difunction-
alization. Mechanistic studies revealed intramolecular oxygen
transfer and oxidative elimination of PhSe group at the sp2
carbon in the formation of ynones as well as the conversion of
sp2 C–Se to sp3 C–Se bond and a SN2 displacement in the for-
mation of oxazoles. Our discovery enriched the mechanism of
selenium catalysis and promoted further design of new reac-
tions by selenium-π-acid catalysis.
Based on the mechanistic studies and previous reports,8 pos-
sible mechanisms for the formation of ynones and oxazoles
are depicted in Scheme 3. First, PhSeSePh is oxidized by N–F
reagent to give electrophilic species PhSeX. It reacts with al-
kyne 1a to form selenirenium ion A,20 followed by the attack
of the phosphonate group in an intramolecular way to yield
intermediate B. Equilibrium between B and C exists and can
be broken by the nucleophilic attack of H2O to form alcohol D
with the aid of base.21 Then, the oxidation of the hydroxy
group on D towards carbonyl group gives intermediate 8. Af-
ter the oxidative syn elimination of selenium motif and hydro-
gen via intermediate E, ynone 2a is formed and the catalyst is
regenerated. It is noted that catalytic deselenenylation via sp2
C–Se bond cleavage was realized for the first time.8 The
mechanism for the formation of oxazoles is somewhat differ-
ent. A stable keteniminium ion G is first formed via selenire-
nium ion F. After the nucleophilic attack of acetonitrile and
the hydrolysis, intermediate 9 is formed. Due to the tautomeri-
zation, intermediate I is generated. It can be further oxidized
to species J. A SN2 displacement of the selenium group by the
carbonyl group and the isomerization with the aid of base
leads to oxazoles 4 and the catalyst species. Interestingly, this
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: XXX
Experimental details, characterization data, mechanistic
studies and NMR spectra of new compounds.
AUTHOR INFORMATION
Corresponding Author
*E-mail: zhaoxd3@mail.sysu.edu.cn
Notes
The authors declare no competing financial interest.
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2881-2884. (b) García-Marín, H.; van der Toorn, J. C.; Mayoral, J. A.;
ACKNOWLEDGMENT
García, J. I.; Arends, I. W. C. E. Glycerol-Based Solvents as Green
Reaction Media in Epoxidations with Hydrogen Peroxide Catalysed
by Bis[3,5-bis(trifluoromethyl)-diphenyl]diselenide. Green Chem.
2009, 11, 1605-1609. (c) Chen, F.; Tan, C. K.; Yeung, Y.-Y. C2-
1
2
3
4
We thank Sun Yat-Sen University, the “One Thousand Youth
Talents” Program of China and the Natural Science Foundation of
Guangdong Province (Grant No. 2014A030312018) for financial
support.
Symmetric
Cyclic
Selenium-Catalyzed
Enantioselective
5
6
7
8
Bromoaminocyclization. J. Am. Chem. Soc. 2013, 135, 1232-1235. (d)
Yu, L.; Li, H.; Zhang, X.; Ye, J.; Liu, J.; Xu, Q.; Lautens, M.
Organoselenium-Catalyzed Mild Dehydration of Aldoximes: An
Unexpected Practical Method for Organonitrile Synthesis. Org. Lett.
2014, 16, 1346-1349. (e) Jin, W.; Zheng, P.; Wong, W.-T.; Lawa, G.-
L. Efficient Selenium-Catalyzed Selective C(sp3)−H Oxidation of
Benzylpyridines with Molecular Oxygen. Adv. Synth. Catal. 2017,
359, 1588-1593. (f) Sancineto, L.; Mangiavacchi, F.; Tidei, C.;
Bagnoli, L.; Marini, F.; Gioiello, A.; Scianowski, J.; Santi, C.
Selenium-Catalyzed Oxacyclization of Alkenoic Acids and Alkenols.
Asian J. Org. Chem. 2017, 6, 988-992. (g) Horibe, T.; Ohmura, S.;
REFERENCES
(1) For book, see: Trost, B. M.; Li, C.-J. Modern Alkyne Chemistry:
Catalytic and Atom‐Economic Transformations; Wiley-VCH: Wein-
heim, Germany, 2014. For selected reviews, see: (a) Hein, J. E.; Fokin,
V. V. Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) and
Beyond: New Reactivity of Copper(I) Acetylides. Chem. Soc. Rev.
2010, 39, 1302-1315. (b) Godoi, B.; Schumacher, R. F.; Zeni, G.
Synthesis of Heterocycles via Electrophilic Cyclization of Alkynes
Containing Heteroatom. Chem. Rev. 2011, 111, 2937-2980.
(2) For selected reviews, see: (a) Fꢀrstner, A. P.; Davies, W.
Catalytic Carbophilic Activation: Catalysis by Platinum and Gold π
Acids. Angew. Chem. Int. Ed. 2007, 46, 3410-3449. (b) Dorel, R.;
Echavarren, A. M. Gold(I)-Catalyzed Activation of Alkynes for the
Construction of Molecular Complexity. Chem. Rev. 2015, 115, 9028-
9072. (c) Fang, G.; Bi, X. Silver-Catalysed Reactions of Alkynes:
Recent Advances. Chem. Soc. Rev. 2015, 44, 8124-8173.
(3) (a) Peng, B.; Huang, X.; Xie, L.-G.; Maulide, N. A. Brønsted
Acid Catalyzed Redox Arylation. Angew. Chem. Int. Ed. 2014, 53,
8718-8721. (b) Wang, Y.; Song, L.-J.; Zhang, X.; Sun, J. Metal-Free
[2+2+2] Cycloaddition of Ynamides and Nitriles: Mild and
Regioselective Synthesis of Fully Substituted Pyridines. Angew.
Chem. Int. Ed. 2016, 55, 9704-9708. (c) Patil, D. V.; Kim, S. W.;
Nguyen, Q. H.; Kim, H.; Wang, S.; Hoang, T.; Shin, S. Brønsted Acid
Catalyzed Oxygenative Bimolecular Friedel-Crafts Type Coupling of
Ynamides. Angew. Chem. Int. Ed. 2017, 129, 3724-3728. (d) Shibuya,
M.; Fujita, S.; Abe, M.; Yamamoto, Y. Brønsted Acid/Silane
Catalytic System for Intramolecular Hydroalkoxylation and
Hydroamination of Unactivated Alkynes. ACS Catal. 2017, 7, 2848-
2852.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Ishihara,
K. Selenium−Iodine
Cooperative Catalyst
for
Chlorocyclization of Tryptamine Derivatives. Org. Lett. 2017, 19,
5525-5528. (h) Akondi, S. M.; Gangireddy, P.; Pickel, T. C.;
Liebeskind, L. S. Aerobic, Diselenide-Catalyzed Redox Dehydration:
Amides and Peptides. Org. Lett. 2018, 20, 538-541. (i) Tao, Z.; Robb,
K. A.; Zhao, K.; Denmark, S. E. Enantioselective, Lewis Base-
Catalyzed Sulfenocyclization of Polyenes. J. Am. Chem. Soc. 2018,
140, 3569-3573.
(8) For recent reviews, see: (a) Ortgies, S.; Breder, A. Oxidative
Alkene Functionalizations via Selenium-π-Acid Catalysis. ACS Catal.
2017, 7, 5828-5840. (b) Guo, R.; Liao, L.; Zhao, X. Electrophilic
Selenium Catalysis with Electrophilic N-F Reagents as the Oxidants.
Molecules 2017, 22, 835-847.
(9) For selected examples, see: (a) Browne, D. M.; Niyomura, O.;
Wirth, T. Catalytic Use of Selenium Electrophiles in Cyclizations.
Org. Lett. 2007, 9, 3169-3171. (b) Trenner, J.; Depken, C.; Weber, T.;
Breder, A. Direct Oxidative Allylic and Vinylic Amination of
Alkenes through Selenium Catalysis. Angew. Chem. Int. Ed. 2013, 52,
8952-8956. (c) Cresswell, A. J.; Eey, S. T.-C.; Denmark, S. E.
Catalytic, Stereospecific syn-Dichlorination of Alkenes. Nat. Chem.
2015, 7, 146-152. (d) Kawamata, Y.; Hashimoto, T.; Maruoka, K. A
Chiral Electrophilic Selenium Catalyst for Highly Enantioselective
Oxidative Cyclization. J. Am. Chem. Soc. 2016, 138, 5206-5209. (e)
Depken, C.; Krätzschmar, F.; Rieger, R.; Rode, K.; Breder, A. Photo-
catalytic Aerobic Phosphatation of Alkenes. Angew. Chem. Int. Ed.
2018, 57, 2459-2463.
(4) (a) Mahdi, T.; Stephan, D. W. Frustrated Lewis Pair Catalyzed
Hydroamination of Terminal Alkynes. Angew. Chem. Int. Ed. 2013,
52, 12418-12421. (b) Tamke, S.; Qu, Z.-W.; Sitte, N. A.; Flörke, U.;
Grimme, S.; Paradies, J. Frustrated Lewis Pair-Catalyzed Cycloisom-
erization
of
1,5-Enynes
via
a
5-endo-dig
Cycliza-
tion/Protodeborylation Sequence. Angew. Chem. Int. Ed. 2016, 55,
4336-4339. (c) Yuan, K.; Wang, S. trans-Aminoboration across Inter-
nal Alkynes Catalyzed by B(C6F5)3 for the Synthesis of Borylated
Indoles. Org. Lett. 2017, 19, 1462-1465. (d) Shibuya, M.; Okamoto,
M.; Fujita, S.; Abe, M.; Yamamoto, Y. Boron-Catalyzed Double
Hydrofunctionalization Reactions of Unactivated Alkynes. ACS Catal.
2018, 8, 4189-4193.
(5) (a) Rodríguez, A.; Moran, W. J. Iodobenzene-Catalyzed
Intramolecular Oxidative Cyclization Reactions of δ-Alkynyl β-
Ketoesters. Org. Lett. 2011, 13, 2220-2223. (b) Yagyu, T.; Takemoto,
Y.; Yoshimura, A.; Zhdankin, V. V.; Saito A. Iodine(III)-Catalyzed
Formal [2+2+1] Cycloaddition Reaction for Metal-Free Construction
of Oxazoles. Org. Lett. 2017, 19, 10, 2506-2509. (c) Okamura, Y.;
Sato, D.; Yoshimura, A.; Zhdankin, V. V.; Saito, A. Iodine(III)-
Mediated/Catalyzed Cycloisomerization-Amination Sequence of N-
Propargyl Carboxamides. Adv. Synth. Catal. 2017, 359, 18, 3243-
3247.
(6) For selected reviews, see: (a) Flanigan, D. M.; Romanov-
Michailidis, F.; White, N. A.; Rovis, T. Organocatalytic Reactions
Enabled by N-Heterocyclic Carbenes. Chem. Rev. 2015, 115, 9307-
9387. (b) Qin, Y.; Zhu, L.; Luo, S. Organocatalysis in Inert C-H Bond
Functionalization. Chem. Rev. 2017, 117, 9433-9520. (c) Zou, Y.-Q.;
Hormann, F. M.; Bach, T. Iminium and Enamine Catalysis in
Enantioselective Photochemical Reactions. Chem. Soc. Rev. 2018, 47,
278-290.
(10) (a) Deng, Z.; Wei, J.; Liao, L.; Huang, H.; Zhao, X.
Organoselenium-Catalyzed,
Hydroxy-Controlled
Regio-
and
Stereoselective Amination of Terminal Alkenes: Efficient Synthesis
of 3‑Amino Allylic Alcohols. Org. Lett. 2015, 17, 1834-1837. (b)
Zhang, X.; Guo, R.; Zhao, X. Organoselenium-Catalyzed Synthesis of
Indoles through Intramolecular C-H Amination. Org. Chem. Front.
2015, 2, 1334-1337. (c) Guo, R.; Huang, J.; Huang, H.; Zhao, X.
Organoselenium-Catalyzed Synthesis of Oxygen- and Nitrogen-
Containing Heterocycles. Org. Lett. 2016, 18, 504-507. (d) Liao, L.;
Guo, R.; Zhao, X. Organoselenium-Catalyzed Regioselective C–H
Pyridination of 1,3-Dienes and Alkenes. Angew. Chem. Int. Ed. 2017,
56, 3201-3205. (e) Guo, R.; Huang, J.; Zhao, X. Organoselenium-
Catalyzed Oxidative Allylic Fluorination with Electrophilic N−F
Reagent. ACS Catal. 2018, 8, 926-930.
(11) (a) Tiecco, M.; Testaferri, L.; Tingoli, M.; Chianelli, D.; Bar-
toli, D. Selenium-Mediated Conversion of Alkynes into α-Dicarbonyl
Compounds. J. Org. Chem. 1991, 56, 4529-4534. (b) Santoro, S.;
Battistelli, B.; Gjoka, B.; Si, C. S.; Testaferri, L.; Tiecco, M.; Santi, C.
Oxidation of Alkynes in Aqueous Media Catalyzed by Diphenyl
Diselenide. Synlett 2010, 1402-1406.
(12) (a) Back, T. G.; Muralidharan, K. R. Formation and
Electrophilic Reactions of Benzeneselenenyl p-Toluenesulfonate.
Preparation and Properties of Addition Products with Acetylenes. J.
Org. Chem. 1991, 56, 2781-2787. (b) Poleschner, H.; Seppelt, K.
Selenirenium and Tellurirenium Ions. Angew. Chem. Int. Ed. 2008, 47,
6461-6464. (c) Zheng, G.; Zhao, J.; Li, Z.; Zhang, Q.; Sun, J.; Sun, H.;
(7) For selected examples, see: (a) Santoro, S.; Santi, C.; Sabatini,
M.; Testaferri, L.; Tiecco, M. Eco-Friendly Olefin Dihydroxylation
Catalyzed by Diphenyl Diselenide. Adv. Synth. Catal. 2008, 350,
ACS Paragon Plus Environment

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Page 6 of 7
Zhang, Q. Highly Regio- and Stereoselective Intermolecular Seleno-
propargylphosphonates. For the reactions of 3-alkynoates, allene is
possible as intermediate since ester-substituted allenes could give
ynones (see Supporting Information).
(21) (a) He, G.; Guo, H.; Qian, R.; Guo, Y.; Fu, C.; Ma, S. Studies
on Highly Regio- and Stereoselective Selenohydroxylation Reaction
of 1,2-Allenyl Phosphine Oxides with PhSeCl. Tetrahedron, 2009, 65,
4877-4889. (b) Li, F.-H.; Cai, Z.-J.; Yin, L.; Li, J.; Wang, S.-Y.; Ji,
S.-J. Silver-Catalyzed Regioselective Fluorination of Carbonyl
Directed Alkynes: Synthesis of α‑Fluoroketones. Org. Lett. 2017, 19,
1662-1665. (c) Yuan, S.-T.; Zhou, H.; Gao, L.; Liu, J.-B.; Qiu, G.
and Thioamination of Alkynes. Chem. Eur. J. 2016, 22, 3513-3518.
(13) (a) Reich, H. J.; Willis, Jr. W. W. Organoselenium Chemistry.
Formation of Acetylenes and Allenes by Syn Elimination of Vinyl
Selenoxides. J. Am. Chem. Soc. 1980, 102, 5967-5968. (b) Back, T.
G.; Collins, S.; Kerr, R. G. Selenosulfonation of Acetylenes:
Preparation of Novel β-(Phenylse1eno)vinyl Sulfones and Their
Conversion to Acetylenic and β-Functionalized Sulfones. J. Org.
Chem. 1983, 48, 3077-3084.
(14) (a) Liu, X.; An, R.; Zhang, X.; Luo, J.; Zhao, X.
Enantioselective Trifluoromethylthiolating Lactonization Catalyzed
by an Indane-Based Chiral Sulfide. Angew. Chem. Int. Ed. 2016, 55,
5846-5850. (b) Luo, J.; Cao, Q.; Cao, X.; Zhao, X. Selenide-
Catalyzed Enantioselective Synthesis of Trifluoromethylthiolated
Tetrahydronaphthalenes by Merging Desymmetrization and
Trifluoromethylthiolation. Nat. Commun. 2018, 9, 527-535. (c) Liu,
X.; Liang, Y.; Ji, J.; Luo, J.; Zhao, X. Chiral Selenide-Catalyzed
1
2
3
4
5
6
7
8
Regioselective
Neighboring-Group-Participated
2,4-
9
Dibromohydration of Conjugated Enynes: Synthesis of 2 ‑ (2,4-
Dibromobut-2-enoyl)benzoate and Its Applications. Org. Lett. 2018,
20, 562-565.
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11
12
13
14
15
16
17
18
19
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21
22
23
24
25
26
27
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57
58
59
60
Enantioselective
Allylic
Reaction
and
Intermolecular
Difunctionalization of Alkenes: Efficient Construction of C-SCF3
Stereogenic Molecules. J. Am. Chem. Soc. 2018, 140, 4782-4786.
(15) (a) Savignac, P.; Iorga, B. Modern Phosphonate Chemistry;
CRC Press: Boca Raton, USA, 2003. (b) Horsman, G. P.; Zechel, D.
L. Phosphonate Biochemistry. Chem. Rev. 2017, 117, 5704-5783.
(16) (a) Öhler, E.; Zbiral, E. Synthesis, Reactions and NMR Spectra
of Dialkyl 2-Bromo-3-Oxo-1-Alkenylphosphonates and Dialkyl 3-
Oxo-1-Alkynylphosphonates. Monatsh. Chem. 1984, 115, 493-508. (b)
Moglie, Y.; Mascarꢁ, E.; Gutierrez, V.; Alonso, F.; Radivoy, G. Base-
Free Direct Synthesis of Alkynylphosphonates from Alkynes and H-
Phosphonates Catalyzed by Cu2O. J. Org. Chem. 2016, 81, 1813-1818.
(c) Yu, Y.; Yang, W.; Pflästerer, D.; Hashmi, A. S. K.
Dehydrogenative Meyer-Schuster-Like Rearrangement:
A Gold-
Catalyzed Reaction Generating an Alkyne. Angew. Chem. Int. Ed.
2014, 53, 1144-1147. (d) Shiroodi, R. K.; Soltani, M.; Gevorgyan, V.
Gold-Catalyzed 1,3-Transposition of Ynones. J. Am. Chem. Soc. 2014,
136, 9882-9885.
(17) (a) Yeh, V. S. C. Recent Advances in the Total Syntheses of
Oxazole-Containing Natural Products. Tetrahedron 2004, 60, 11995-
12042. (b) Davyt, D.; Serra, G. Thiazole and Oxazole Alkaloids:
Isolation and Synthesis. Mar. Drugs 2010, 8, 2755-2780. (c) Jin, Z.
Muscarine, Imidazole, Oxazole and Thiazole Alkaloids. Nat. Prod.
Rep. 2016, 33, 1268-1317.
(18) (a) Davies, P. W.; Cremonesi, A.; Dumitrescu, L. Intermolecu-
lar and Selective Synthesis of 2,4,5-Trisubstituted Oxazoles by a
Gold-Catalyzed Formal [3+2] Cycloaddition. Angew. Chem. Int. Ed.
2011, 50, 8931-8935. (b) He, W.; Li, C.; Zhang, L. An Efficient
[2+2+1] Synthesis of 2,5-Disubstituted Oxazoles via Gold-Catalyzed
Intermolecular Alkyne Oxidation. J. Am. Chem. Soc. 2011, 133,
8482-8485. c) Luo, Y.; Ji, K.; Li, Y.; Zhang, L. Tempering the Reac-
tivities of Postulated α-Oxo Gold Carbenes Using Bidentate Ligands:
Implication of Tricoordinated Gold Intermediates and the Develop-
ment of an Expedient Bimolecular Assembly of 2,4-Disubstituted
Oxazoles. J. Am. Chem. Soc. 2012, 134, 17412-17415. (d) Li, X.;
Huang, L.; Chen, H.; Wu, W.; Huang, H.; Jiang, H. Copper-Catalyzed
Oxidative [2+2+1] Cycloaddition: Regioselective Synthesis of 1,3-
Oxazoles from Internal Alkynes and Nitriles. Chem. Sci. 2012, 3,
3463-3467. (e) Rassadin, V. A.; Boyarskiy, V. P.; Kukushkin, V. Yu.
Facile Gold-Catalyzed Heterocyclization of Terminal Alkynes and
Cyanamides Leading to Substituted 2-Amino-1,3-Oxazoles. Org. Lett.
2015, 17, 3502-3505. (f) Mallick, R. K.; Prabagar, B.; Sahoo, A. K.
Regioselective Synthesis of 2,4,5-Trisubstituted Oxazoles and Ketene
Aminals via Hydroamidation and Iodo-Imidation of Ynamides. J. Org.
Chem. 2017, 82, 10583-10594.
(19) Oxazole was observed as a by-product in trace amounts. See:
Tingoli, M.; Mazzella, M.; Panunzi, B.; Tuzi, A. Elemental Iodine or
Diphenyl Diselenide in the [Bis(trifluoroacetoxy)-iodo]benzene-
Mediated Conversion of Alkynes into 1,2-Diketones. Eur. J. Org.
Chem. 2011, 399-404.
(20) Our mechanistic studies did not support that the formation of
ynones
went
through
an
allene
intermediate
with
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