Synthesis and Properties of 1-Acyl Triazenes

Article abstract of DOI:10.1021/acs.orglett.9b02248

1-Acyl triazenes can be prepared by acid-catalyzed hydration, gold/iodine-catalyzed oxidation, or oxyhalogenation of 1-alkynyl triazenes. Crystallographic analyses reveal a pronounced effect of the acyl group on the electronic structure of the triazene fu

Full text of DOI:10.1021/acs.orglett.9b02248

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Synthesis and Properties of 1‑Acyl Triazenes
Iris R. Landman, Emilio Acuna-Bolomey, Rosario Scopelliti, Farzaneh Fadaei-Tirani,
̃
and Kay Severin*
́
́
́
Institut des Sciences et Ingenierie Chimiques, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland
S
* Supporting Information
ABSTRACT: 1-Acyl triazenes can be prepared by acid-
catalyzed hydration, gold/iodine-catalyzed oxidation, or oxy-
halogenation of 1-alkynyl triazenes. Crystallographic analyses
reveal a pronounced effect of the acyl group on the electronic
structure of the triazene function. 1-Acyl triazenes display high
thermal stability, and only moderate sensitivity toward
hydrolysis. They are compatible with basic and oxidative
conditions, allowing subsequent transformation. Under acidic
conditions, 1-acyl triazenes act as acylation reagents.
riazenes with acyl groups attached to the N3 atom
(Figure 1) have been studied extensively over the past
so far. We found that 1-acyl triazenes are accessible by
hydration or oxidation of 1-alkynyl triazenes, and details about
these reactions are given below.
T
decades in medicinal and synthetic chemistry.1 These
compounds are typically prepared by acylation of 1,3-
disubstituted triazenes.1,2 Alternative synthetic pathways
include the reaction of deprotonated amides with diazonium
salts,3 the condensation of hydrazides with aromatic nitroso
compounds,4 or the reaction of benzoyl azide with a Grignard
reagent.5 3-Acyl triazenes have found considerable interest in
medicinal chemistry, and numerous bioactive compounds have
been reported in the literature.6 In this context, the reactivity
of 3-acyl triazenes has been studied in detail, from both a
theoretical7 and experimental6,8 point of view. 3-Acyl triazenes
have also been used as precursors for aminyl radicals,9 as
acylating agents,10 and as chemodosimeters for cyanide.11
The chemistry described in this report was enabled by our
recent discovery that 1-alkynyl triazenes can be prepared from
lithium amides, alkynyl Grignard reagents, and nitrous
oxide.15,16 These heteroatom-substituted alkynes display a
similar reactivity as ynamides.17 For example, ketenes react
with 1-alkynyl triazenes to give [2 + 2] cycloaddition products
under mild conditions.17f Ynamides can be hydrated to give N-
acyl sulfonamides.18 An analogous reaction with 1-alkynyl
triazenes would give 1-acyl triazenes, and we therefore
examined reaction conditions for the controlled hydrolysis of
1-alkynyl triazenes. The published procedures for the
hydrolysis of ynamides involve acids or Lewis acids. The
triazene group is known to be acid-sensitive.1 Therefore, the
challenge was to find conditions which would allow the
hydration of the triple bond without cleavage of the triazene
function.
Initial attempts to hydrolyze 1-alkynyl triazenes in the
presence of Ag(I) salts showed that the desired products can
be formed (see Supporting Information, SI, Table S3.1).
However, high catalyst concentrations were needed, and
problems with purification were encountered. Switching to
acetic acid catalysis18b was found to be advantageous.
Moderate to good yields were obtained for alkynyl triazenes
containing various substituents at the triple bond (1−6,
Scheme 1). In situ NMR experiments revealed small amounts
Figure 1. 3-Acyl triazenes versus 1-acyl triazenes.
In contrast to the well-established chemistry of 3-acyl
triazenes, there are hardly any reports about triazenes with
carbonyl groups attached to the N1 atom. Triazenes with 1-
carbamoyl and 1-alkoxycarbonyl groups have been prepared by
oxidation of functionalized triazanes.12 Furthermore, there are
reports about benzo[1,2,3]triazine-4(3H)-one derivatives,13
which can be regarded as cyclic (covalent connection between
N1 and N3)14 acyl triazenes. A general synthetic method for
synthesizing acyclic 1-acyl triazenes (Figure 1) is not available
+
of iPr2NH2 as a side product. The ammonium salt is formed
by acid-induced cleavage of the triazene function. However, it
is worth noting that the products are less acid-sensitive than a
standard aryl triazene (PhN3iPr2) under the given conditions
(SI, Figure S10.1).
Received: July 5, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b02248
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Letter
Scheme 1. Acetic Acid Catalyzed Hydration of Alkynyl
Triazenes
Scheme 2. Au-Catalyzed Oxidation of Alkynyl Triazenes
a
The reaction was performed in a closed vial at 100 °C with 2 equiv
of CH3CO2H.
a
b
Only the E isomer observed. The E/Z mixture could not be fully
The hydration of a phenylethynyl triazene (R2 = Ph) turned
out to be more difficult. For this substrate, an increased
temperature of 100 °C and 2 equiv of acetic acid were found to
be advantageous. Still, the corresponding acyl triazene 7 was
isolated in only 36% yield. Most likely, these hydration
reactions are initiated by protonation of the alkyne at the β-
carbon atom, and this position is less nucleophilic in the case
of the phenylethynyl triazene. Variation of the alkyl
substituents at the N3 position is possible, as evidenced by
the successful synthesis of the acyl triazenes 8 and 9.
separated.
a
Scheme 3. Double Oxidation of Alkynyl Triazenes
Next, we explored the oxidation of 1-alkynyl triazenes with
pyridine N-oxides in the presence of Au(I) catalysts.19,20
Screening of different catalysts and reaction conditions showed
that (JohnPhos)AuCl in combination with AgNTf2 (both 5
mol %) and pyridine N-oxide can be used for the clean
formation of the olefinic acyl triazene 10 (SI, Table S4.1). The
optimized reactions conditions were then used to synthesize
the acryloyl triazenes 11−16, which were obtained in moderate
to good yields (Scheme 2). The reactions gave predominantly
the E isomer. The oxidation of internal alkynes with pyridine
N-oxides is prone to give mixtures of regioisomers.21 In our
case, oxygen atom transfer was perfectly site-specific, as it was
observed for ynamides.19 The high selectivity can be attributed
to the polarization of the triple bond of alkynyl triazenes.17f
The likely mechanism of the reaction involves a nucleophilic
attack of the pyridine N-oxide at the Cα position of the Au-
activated triple bond, followed by N−O bond rupture and
formation of an α-oxo gold carbenoid.22 Product formation
then occurs via a [1,2]H shift (or [1,2]Me shift in the case of
16).
If [1,2] shifts are not possible, the intermediate gold
carbenoid is susceptible to another attack by pyridine N-oxide,
leading to a double oxidation of the alkyne.19 Arylethynyl
triazenes are not able to undergo [1,2] shifts after a first
oxidation, and they appeared to be suited substrates for the
synthesis of 1,2-diketones. First test reactions with a phenyl-
ethynyl triazene showed that Au-catalyzed double oxidation
reactions can indeed be realized when an excess of pyridine N-
oxide is employed (Scheme 3). However, we also examined if
the reaction could be catalyzed by iodine,23 and the yield for
the metal-free oxidation was superior (for 17: 85 vs 61%).
a
Conditions A: 2-chloro pyridine N-oxide (R3 = Cl, 3 equiv), I2 (0.5
equiv), acetonitrile (0.1 M), rt, 50 min. Conditions B: pyridine N-
oxide (R3 = H, 2.2 equiv), (JohnPhos)AuCl (10 mol %), AgNTf2 (10
b
mol %), 1,2-dichloroethane (0.2 M), 70 °C, 1.5 h. Only conditions B
gave the desired product.
Triazenes with p-methoxyphenyl or p-fluorophenyl groups
could be oxidized with similar yields (18 and 19). When using
a triazene with a cyclohexenyl instead of an aryl group attached
to the triple bond, the I2 activation method was not successful.
Here, the Au-catalyzed procedure turned out to be better,
allowing the isolation of the diketone 20 in 42% yield. Varying
the alkyl substituents on N3 (Cy or Me instead of iPr) gave the
corresponding acyl triazenes 21 and 22 in good yields using
the I2-based procedure. It is worth noting that the products are
thermally very stable. For compound 17, for example, we could
detect only traces of decomposition after heating a solution in
DMSO-d6 for 5 days at 140 °C.
To expand the scope even further, we examined oxy-
halogenation reactions24 with alkynyl triazenes. Using N-
bromosuccinimide (NBS), we were able to obtain the
B
DOI: 10.1021/acs.orglett.9b02248
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Letter
dibrominated 1-acyl triazenes 23−27 in mostly good yields
(Scheme 4). The reactions can be performed under mild
Scheme 4. Oxyhalogenation of 1-Acyl Triazenes
conditions (0 °C) without a catalyst, which is in contrast to
most oxyhalogenation reactions with NBS described in the
literature.24,25 We attribute the ease of the transformation to
the high intrinsic reactivity of the alkynyl triazenes. Changing
NBS to N-chlorosuccinimide (NCS) led to the formation of α-
dichlorinated acyl triazene 28 in 71% yield. With N-
iodosuccinimide (NIS), on the other hand, we were not able
to prepare the corresponding diiodo compound.
After having established methodologies for the synthesis of
four types of 1-acyl triazenes, we focused on exploring the
properties of these new compounds. The solid state structures
of 2, 11-E, 16, 18, 20, and 21 were determined by single crystal
X-ray diffraction (Figure 2a).
Figure 2. Crystal structures of 1-acyl triazenes (a), N−N bond
lengths of 1-aryl- and 1-acyl triazenes (b), and mesomeric structures
of 1-acyl triazenes (c).
For all six compounds, the N−CO group was found to be
in plane with the triazene group, indicating electronic
communication between the two. The electron-withdrawing
effect of the carbonyl group has a strong effect on the structure
of the triazene. Notably, the formal N−N single bond between
N3 and N2 is of comparable length as the formal NN
double bond between N2 and N1 (for 16, 18, 20, and 21, the
N2−N3 bond is even shorter than the N1−N2 bond). The
pronounced influence of the acyl group is evident when
comparing the structures of 1-acyl triazenes with what is found
for 3,3-dialkyl-1-aryl triazenes. An analysis of 67 compounds
found in the CCDC database showed that these triazenes all
display a “normal” behavior, with the formal N−N single bond
N2−N3 bond cleavage would give highly reactive acyldiazo-
nium compounds, which would act as acylation agents. In
order to examine if such reactivity can indeed be observed, we
have analyzed reactions of the 1-acyl triazenes 1, 16, and 17
with HOTf in the presence of different nucleophiles (water,
methanol, aniline, and anisole). In most cases, a clean acylation
reaction was observed (Scheme 5; for details, see SI). Attempts
a
Scheme 5. 1-Acyl Triazenes as Acylating Agents
being longer than the formal NN double bond (N2−N3av.
=
1.33 Å, N1−N2av. = 1.27 Å; Figure 2b). The remarkably short
N2−N3 bonds of 1-acyl triazenes imply that the resonance
forms B and C contribute significantly to describing the
electronic structure (Figure 2c).26
a
1
Yields and product ratios were determined by H NMR spectros-
copy. Conditions: HOTf (2 equiv), NuH = D2O/CD3CN/D2O, 9:1,
0.05 M, rt (for 23: 70 °C), 11−90 min; NuH = CD3OD: neat, 0.05
M, rt, 44−59 min; NuH = aniline (2 equiv): CD3CN (0.05 M), 70
°C, 70 min−18 h; NuH = anisole (2 equiv):CD3CN (0.05 M), 70 °C,
20−21 h.
3-Acyl triazenes are known to undergo facile hydrolysis.8c In
order to assess the hydrolytic stability of 1-acyl triazenes, we
have analyzed solutions of 3 in D2O/d6-acetone (4:1) by NMR
spectroscopy (compound 3 was chosen because its solubility in
aqueous solution). After heating for 12 days at 50 °C, only
partial hydrolysis was observed (28%). Heating for 22 h to
reflux resulted in 61% hydrolysis. These results show that 1-
acyl triazenes have a comparatively low susceptibility to
hydrolyze.
to perform more challenging acylation reactions with benzene
as a nucleophile were not successful. We have also examined
acylation reactions with the brominated triazene 23. With
water and methanol, the expected products were obtained in
76% and 94% yield, respectively, but reactions with anisole and
aniline gave a mixture of products, and more detailed analyses
were not performed.
As mentioned earlier, triazenes are acid-sensitive com-
pounds. Protonation typically induces cleavage of the N2−N3
bond, with concomitant formation of ammonium and
diazonium ions.1 In the case of 1-acyl triazenes, acid-induced
C
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Letter
Finally, we have briefly examined reactions under nonacidic
conditions (Scheme 6). Oxidative conditions are compatible
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: kay.severin@epfl.ch.
ORCID
a
Scheme 6. Reactions of the 1-Acyl Triazenes 16 and 1
Rosario Scopelliti: 0000-0001-8161-8715
Farzaneh Fadaei-Tirani: 0000-0002-7515-7593
Kay Severin: 0000-0003-2224-7234
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by funding from the Swiss National
Science Foundation and from the Ecole Polytechnique
■
a
Conditions: (29) DCM (0.2 M), mCPBA (1.1 equiv), rt, 2 h,
isolated yield; (30) LDA (1.42 equiv), prenyl bromide (1.5 equiv) in
THF, −78 °C, isolated yield.
́
́
Federale de Lausanne (EPFL).
REFERENCES
■
̈
̈
(1) For reviews, see: (a) Kolmel, D. K.; Jung, N.; Brase, S. Aust. J.
Chem. 2014, 67, 328−336. (b) Kimball, D. B.; Haley, M. M. Angew.
Chem., Int. Ed. 2002, 41, 3338−3351. (c) Nifontov, V. I.; Bel’skaya, N.
P.; Shtokareva, E. A. Pharm. Chem. J. 1993, 27, 652−665.
(d) Vaughan, K.; Stevens, M. F. G. Chem. Soc. Rev. 1978, 7, 377−397.
(2) (a) Smith, R. H., Jr.; Mehl, A. F.; Shantz, D. L.; Chmurny, G. N.;
Michejda, C. J. J. Org. Chem. 1988, 53, 1467−1471. (b) Smith, R. H.,
Jr.; Michejda, C. J. Synthesis 1983, 1983, 476−477.
with the triazene function, as evidenced by the synthesis of
epoxide 29. Strongly basic conditions are also tolerated, and we
were able to perform an alkylation reaction with prenyl-
bromide via an enolate intermediate generated by LDA (30).
In conclusion, we have shown that 1-acyl triazenes can be
prepared by hydrolysis or oxidation of 1-alkynyl triazenes.
Using these methods, we were able to synthesize for the first
time a variety of structurally diverse 1-acyl triazenes. The acyl
group at the N1 position was found to have a strong influence
on the physical and chemical properties of the triazenes.
Crystallographic analyses revealed extremely short N2−N3
bond lengths. Accordingly, the energy barrier for rotation
around this bond is much higher than what has been reported
for other triazenes. The new 1-acyl triazenes are thermally
robust compounds with a low susceptibility to hydrolyze.
Under acidic conditions, they act as acylating agents. Basic or
oxidative conditions, on the other hand, are well tolerated by
the triazene function.
In the present work, we have focused on the synthesis and
the properties of 1-acyl triazenes. However, investigating the
biological activity of these compounds appears worthwhile.
The bioactivity of previously reported triazenes is generally
related to the fact that they represent masked alkylating
agents.1,6 1-Acyl triazenes act as masked acylating, rather than
alkylating, agents. Therefore, these compounds might display a
biological activity which is distinct from that of other triazenes.
(3) (a) Wanner, M. J.; Koch, M.; Koomen, G.-J. J. Med. Chem. 2004,
47, 6875−6883. (b) Beukers, M. W.; Wanner, M. J.; Von Frijtag
Drabbe Kunzel, J. K.; Klaasse, E. C.; IJzerman, A. P.; Koomen, G.-J. J.
̈
Med. Chem. 2003, 46, 1492−1503. (c) Curtin, D. Y.; Druliner, J. D. J.
Org. Chem. 1967, 32, 1552−1557.
(4) Ito, S.; Fukuyama, T. J. Org. Chem. 1971, 36, 2008−2009.
(5) Bertho, A. J. Prakt. Chem. 1927, 116, 101−117.
(6) For examples, see: (a) Vajs, J.; Proud, C.; Brozovic, A.; Gazvoda,
̌
M.; Lloyd, A.; Roper, D. I.; Osmak, M.; Kosmrlj, J.; Dowson, C. G.
Eur. J. Med. Chem. 2017, 127, 223−234. (b) Sousa, A.; Santos, F.;
Gaspar, M. M.; Calado, S.; Pereira, J. D.; Mendes, E.; Francisco, A. P.;
Perry, M. J. Bioorg. Med. Chem. 2017, 25, 3900−3910. (c) Mouhri, Z.
S.; Goodfellow, E.; Kelley, S. P.; Stein, R. S.; Rogers, R. D.; Jean-
Claude, B. J. Molecules 2017, 22, 1183. (d) Cappoen, D.; Vajs, J.;
̌
Uythethofken, C.; Virag, A.; Mathys, V.; Kocevar, M.; Verschaeve, L.;
Gazvoda, M.; Polanc, S.; Huygen, K.; Kosmrlj, J. Eur. J. Med. Chem.
̌
2014, 77, 193−203. (e) Monteiro, A. S.; Almeida, J.; Cabral, G.;
Severino, P.; Videira, P. A.; Sousa, A.; Nunes, R.; Pereira, J. D.;
Francisco, A. P.; Perry, M. J.; Mendes, E. Eur. J. Med. Chem. 2013, 70,
1−9. (f) Perry, M. J.; Mendes, E.; Simplício, A. L.; Coelho, A.; Soares,
R. V.; Iley, J.; Moreira, R.; Francisco, A. P. Eur. J. Med. Chem. 2009,
44, 3228−3234.
(7) Ozment, J. L.; Schmiedekamp, A. M.; Schultz-Merkel, L. A.;
Smith, R. H., Jr.; Michejda, C. J. J. Am. Chem. Soc. 1991, 113, 397−
405.
ASSOCIATED CONTENT
■
S
* Supporting Information
(8) (a) Carvalho, E.; Iley, J.; Rosa, E. J. Chem. Soc., Perkin Trans. 2
1993, 865−870. (b) Smith, R. H., Jr.; Wladkowski, B. D.; Herling, J.
A.; Pfaltzgraff, T. D.; Taylor, J. E.; Thompson, E. J.; Pruski, B.; Klose,
J. R.; Michejda, C. J. J. Org. Chem. 1992, 57, 6448−6454. (c) Smith,
R. H., Jr.; Wladkowski, B. D.; Herling, J. A.; Pfaltzgraff, T. D.; Pruski,
B.; Klose, J.; Michejda, C. J. J. Org. Chem. 1992, 57, 654−661.
(d) Smith, R. H., Jr.; Mehl, A. F.; Hicks, A.; Denlinger, C. L.; Kratz,
L.; Andrews, A. W.; Michejda, C. J. J. Org. Chem. 1986, 51, 3751−
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b02248.
Experimental details and analytical data of the new
compounds (PDF)
̌ ̌
3757. (e) Ludwig, M.; Pytela, O.; Vecera, M. Collect. Czech. Chem.
Accession Codes
̌
̌
̌
Commun. 1981, 46, 3104−3109. (f) Pytela, O.; Vecera, M.; Vetesník,
CCDC 1921563−1921568 contain the supplementary crys-
tallographic 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
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
P. Collect. Czech. Chem. Commun. 1981, 46, 898−905. (g) Pytela, O.;
̌
̌
̌
Vecera, M.; Vetesník, P. Collect. Czech. Chem. Commun. 1980, 45,
1269−1278.
(9) Lu, H.; Li, C. Tetrahedron Lett. 2005, 46, 5983−5985.
̌
̌
̌
(10) Stefane, B.; Cernigoj, U.; Kocevar, M.; Polanc, S. Tetrahedron
Lett. 2001, 42, 6659−6662.
D
DOI: 10.1021/acs.orglett.9b02248
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(11) Chung, Y.; Lee, H.; Ahn, K. H. J. Org. Chem. 2006, 71, 9470−
9474.
(12) (a) Glowacki, A.; Jeux, V.; Gasnier, G.; Joucla, L.; Jacob, G.;
̂
Lacote, E. Synlett 2018, 29, 566−570. (b) Egger, N.; Hoesch, L.;
Dreiding, A. S. Helv. Chim. Acta 1983, 66, 1416−1426.
(13) (a) Shi, W.-M.; Ma, X.-P.; Pan, C.-X.; Su, G.-F.; Mo, D.-L. J.
Org. Chem. 2015, 80, 11175−11183. (b) Dunkin, I. R.; Lynch, M. A.;
Withnall, R.; Boulton, A. J.; Henderson, N. J. Chem. Soc., Chem.
Commun. 1989, 1777−1778. (c) Boulton, A. J.; Devi, P. J. J. Chem.
Soc., Chem. Commun. 1988, 631−632.
(14) For a classification of ‘acyclic’ and ‘cyclic’ triazenes, see: Patil,
S.; White, K.; Bugarin, A. Tetrahedron Lett. 2014, 55, 4826−4829.
(15) Kiefer, G.; Riedel, T.; Dyson, P. J.; Scopelliti, R.; Severin, K.
Angew. Chem., Int. Ed. 2015, 54, 302−305.
(16) For the use of nitrous oxide in synthetic chemistry, see: Severin,
K. Chem. Soc. Rev. 2015, 44, 6375−6386.
(17) (a) Tan, J.-F.; Bormann, C. T.; Chadwick, F. M.; Severin, K.;
Cramer, N. J. Am. Chem. Soc. 2019, 141, 10372−10383. (b) Wezeman,
T.; Scopelliti, R.; Tirani, F. F.; Severin, K. Adv. Synth. Catal. 2019,
361, 1383−1388. (c) Suleymanov, A. A.; Scopelliti, R.; Tirani, F. F.;
Severin, K. Adv. Synth. Catal. 2018, 360, 4178−4183. (d) Kossler, D.;
Perrin, F.; Suleymanov, A. A.; Kiefer, G.; Scopelliti, R.; Severin, K.;
Cramer, N. Angew. Chem., Int. Ed. 2017, 56, 11490−11493.
(e) Jeanbourquin, L. N.; Scopelliti, R.; Fadaei Tirani, F.; Severin, K.
Org. Lett. 2017, 19, 2070−2073. (f) Perrin, F.; Kiefer, G.;
Jeanbourquin, L.; Racine, S.; Perrotta, D.; Waser, J.; Scopelliti, R.;
Severin, K. Angew. Chem., Int. Ed. 2015, 54, 13393−13396.
(18) (a) Huang, H.; Tang, L.; Xi, Y.; He, G.; Zhu, H. Tetrahedron
Lett. 2016, 57, 1873−1876. (b) Xu, S.; Liu, J.; Hu, D.; Bi, X. Green
Chem. 2015, 17, 184. (c) Ghosh, N.; Nayak, S.; Sahoo, A. K. Chem. -
Eur. J. 2013, 19, 9428−9433. (d) Compain, G.; Jouvin, K.; Martin-
Mingot, A.; Evano, G.; Marrot, J.; Thibaudeau, S. Chem. Commun.
2012, 48, 5196−5198. (e) Jin, X.; Yamaguchi, K.; Mizuno, N. Chem.
Lett. 2012, 41, 866−867.
(19) Davies, P. W.; Cremonesi, A.; Martin, N. Chem. Commun.
2011, 47, 379−381.
(20) Dorel, R.; Echavarren, A. M. Chem. Rev. 2015, 115, 9028−
9072.
(21) Lu, B.; Zhang, L. J. Am. Chem. Soc. 2010, 132, 14070−14072.
̌
̌
́
́
(22) Schulz, J.; Jasíkova, L.; Skríba, A.; Roithova, J. J. Am. Chem. Soc.
2014, 136, 11513−11523.
(23) Kim, S. W.; Um, T.-W.; Shin, S. J. Org. Chem. 2018, 83, 4703−
4711.
(24) (a) Finck, L.; Brals, J.; Pavuluri, B.; Gallou, F.; Handa, S. J. Org.
Chem. 2018, 83, 7366−7372. (b) Sadhukhan, S.; Baire, B.
ChemistrySelect 2017, 2, 8500−8503. (c) Liu, J.; Li, W.; Wang, C.;
Li, Y.; Li, Z. Tetrahedron Lett. 2011, 52, 4320−4323. (d) Heasley, V.
L.; Shellhamer, D. F.; Chappell, A. E.; Cox, J. M.; Hill, D. J.;
McGovern, S. L.; Eden, C. C. J. Org. Chem. 1998, 63, 4433−4437.
(25) For the oxyhalogenation of alkynes with NXS reagents, ionic
and radical mechanisms have been discussed. In our case, the
involvement of radicals seems likely because the reaction was found to
be light sensitive. When the synthesis of 23 was performed in the
strict absence of light, we were able to detect a significant amount of a
monobrominated acyl triazene in the addition of 23. When the
reaction was carried out under ambient light, the monobrominated
triazene was not detected.
(26) A high energy barrier for rotation around the N2−N3 bond was
confirmed by VT-NMR experiments. For details, see the SI.
E
DOI: 10.1021/acs.orglett.9b02248
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