Cationic ruthenium complex of the formula [RuCl(2,6-diacetylpyridine)(PPh3)2]BArF and its catalytic activity in the formation of enol esters

Article abstract of DOI:10.1016/j.tetlet.2018.01.029

A new ruthenium 2,6-diacetylpyridine complex was synthesized and applied in the atom-economic synthesis of enol esters through Markovnikov-directed addition of carboxylic acids to terminal alkynes. The ruthenium complex [RuCl(dap)(PPh₃)₂]⁺BArF^? was synthesized from [RuCl₂(PPh₃)₂] and the corresponding ligand 2,6-diacetylpyridine (dap). The complex was characterized structurally. The new ruthenium complex was utilized under ambient conditions as a catalyst in the Markovnikov addition of carboxylic acids to terminal alkynes to afford the corresponding enol esters in 93% to 52% isolated yields (85 °C, 16 h reaction time, 1 mol% catalyst loading).

Full text of DOI:10.1016/j.tetlet.2018.01.029

Tetrahedron Letters xxx (2018) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Cationic ruthenium complex of the formula [RuCl(2,6-diacetylpyridine)
(
PPh ) ]BArF and its catalytic activity in the formation of enol esters
3
2
Matthew J. Stark , Douglas T. Tang , Nigam P. Rath a,b, Eike B. Bauer a,
a
a
⇑
a
University of Missouri – St. Louis, Department of Chemistry and Biochemistry, One University Boulevard, St. Louis, MO 63121, USA
Center for Nanoscience, University of Missouri – St. Louis, St. Louis, MO 63121, USA
b
a r t i c l e i n f o
a b s t r a c t
Article history:
A new ruthenium 2,6-diacetylpyridine complex was synthesized and applied in the atom-economic syn-
thesis of enol esters through Markovnikov-directed addition of carboxylic acids to terminal alkynes. The
ruthenium complex [RuCl(dap)(PPh ) ] BArF was synthesized from [RuCl (PPh ) ] and the correspond-
3 2 2 3 2
ing ligand 2,6-diacetylpyridine (dap). The complex was characterized structurally. The new ruthenium
complex was utilized under ambient conditions as a catalyst in the Markovnikov addition of carboxylic
acids to terminal alkynes to afford the corresponding enol esters in 93% to 52% isolated yields (85 °C, 16 h
reaction time, 1 mol% catalyst loading).
Received 2 December 2017
Revised 8 January 2018
Accepted 10 January 2018
Available online xxxx
+
À
Keywords:
Ruthenium complexes
Homogeneous catalysis
Vinyl esters
Ó 2018 Elsevier Ltd. All rights reserved.
Transition metal Lewis acids
Introduction
Several methods to access enol esters are known; among them
are Bayer-Villiger-type oxidation of
the cross coupling of alkenyltrifluoroborate salts with carboxylic
a
,b-unsaturated ketones13 or
Alkynes are valuable starting materials in organic synthesis, and
their transformations can produce a variety of compound classes.
Many of these transformations are transition-metal catalyzed,
and the palladium-catalyzed Sonogashira coupling between termi-
1
4
acids. The addition of carboxylic acids to terminal alkynes is
attractive because these starting materials are readily available
and the method is atom-economical.
1
nal alkynes and aryl- or vinyl halides is a prominent example. The
Well-characterized ruthenium complexes play a prominent role
in organometallic catalysis; they can be thoroughly characterized
using conventional analytical techniques and tend to be configura-
addition of carboxylic acids to terminal alkynes is an atom-eco-
nomical reaction to afford enol esters, and the reaction requires
promotion by a catalyst.2 The reaction can generate different
regioisomers; Markovnikov addition provides the corresponding
geminal enol esters A, whereas anti-Markovnikov addition leads
to the corresponding (E) and (Z) enol esters B (Scheme 1). Control
of the regioselectivity is, thus, crucial for the reaction to be syn-
thetically useful. Ruthenium catalysts are widely employed for
15
tionally stable. Cationic ruthenium complexes can serve as mild
Lewis acids in solution, and are consequently able to exhibit cat-
alytic activity in cases where Lewis acids are the catalytically active
1
6
species.
As part of our continuing research program centered around
1
7
ruthenium complexes, we are in continuous search for well-
defined ruthenium complexes to be applied as catalysts. The
majority of the ruthenium catalysts for the title reaction are based
on fairly uncomplicated and/or commercial ruthenium complexes
3
the reaction since the pioneering work of Shvo. There are catalyst
systems known that produce primarily the Markovnikov enol
4
esters A, and others that give mainly the anti-Markovnikov prod-
ucts B.5 Basic additives,6 the solvent7 or the architecture and the
3,4a,5a
4a,b,5a,6,9b
bearing
a
carbonyl
monodentate phosphine,
8
7
4c
electronic nature of the ruthenium catalyst may have an influence
on the regioselectivity. The addition of carboxylic acids to internal
alkynes is less common but it has been reported as well.
hydrido, or carboxylate ligands. It has been demonstrated that
the ligand structure and its electronic properties can have an
influence on the selectivity of the reaction. However, systematic
9
6
The resulting enol esters themselves are valuable starting mate-
investigations of the metal complex structure on the selectivity
of the title reactions are scarce. The reaction requires elevated tem-
peratures to proceed and catalyst stability at higher temperatures
is not very well investigated.
10
rials for example in polymerization reactions, in acylation reac-
tions,1 and in a number of other organic transformations.
1
12
Based on these considerations, we were searching for a new
ruthenium complex architecture for the title reaction, that would
⇑
Corresponding author.
E-mail address: bauere@umsl.edu (E.B. Bauer).
https://doi.org/10.1016/j.tetlet.2018.01.029
040-4039/Ó 2018 Elsevier Ltd. All rights reserved.
0
Please cite this article in press as: Stark M.J., et al. Tetrahedron Lett. (2018), https://doi.org/10.1016/j.tetlet.2018.01.029

2
M.J. Stark et al. / Tetrahedron Letters xxx (2018) xxx–xxx
Fig. 1. Molecular structure of [RuCl(dap)(PPh
3 2
) ]BArF depicted with 50% probabil-
ity ellipsoids; H atoms and the counter ion are omitted for clarity. Key bond lengths
(
(
Å) and angles (°): Ru(1)–N(1), 1.990(4); Ru(1)–O(1), 2.141(3); Ru(1)–O(2), 2.082
3); Ru(1)–P(1), 2.3220(13); Ru(1)–P(2) 2.3855(13); Ru(1)–Cl(1) 2.4210(12); N(1)–
Ru(1)–P(1), 92.54(12); N(1)–Ru(1)–P(2), 169.54(12); P(1)–Ru(1)–P(2), 97.54(5); N
(1)–Ru(1)–Cl(1), 83.38(11); P(1)–Ru(1)–Cl(1), 173.19(4); P(2)–Ru(1)–Cl(1), 86.84
Scheme 1. Enol ester synthesis.
(
4); O(1)–Ru–O(2), 154.01(14).
be tunable and that would show high promise of thermal stability.
As mentioned, mainly monodentate ligands have been employed
previously. We were wondering whether ruthenium complexes
bearing tridentate ligands can be employed as catalysts in the for-
mation of enol esters. We envisaged 2,6-diacetylpyridines as a tun-
able ligand platform, and set out to investigate its ruthenium
complex as catalyst for the title reaction. Herein, we present the
synthesis and structural characterization of a 2,6-diacetylpyridine
ruthenium complex and its application as catalyst for the regiose-
lective addition of carboxylic acids to terminal alkynes. To the best
of our knowledge, it is the first ruthenium catalyst bearing a tri-
dentate ligand that promotes this reaction.
reveals that the 2,6-diacetylpyridine ligand is coordinated to the
ruthenium center through the nitrogen and the two oxygen atoms
in a tridentate fashion. The O(1)–Ru–O(2) ‘‘bite” angle of the 2,6-
diacetylpyridine ligand is 154°. This angle is smaller than the
1
80° angle in an ideal octahedral complex, which is believed to
be responsible for the fact that the complex is somewhat distorted.
The two PPh ligands take a cis position to each other, which is in
3
3
1
1
accordance with the P{ H} NMR spectrum of the complex. The
bond lengths are comparable to other, neutral ruthenium chloro
1
7a,17b
PPh
3
complexes,
and it appears that the positive charge has
no profound impact on the bond lengths around the ruthenium
center.
Syntheses of the ruthenium complex
Catalytic investigations with the ruthenium complex [RuCl
(
dap)(PPh
3 2
) ]BArF
To the best of our knowledge, ruthenium complexes bearing a
tridentate 2,6-diacetylpyridine ligand are unknown. Accordingly,
The new complex was subsequently investigated as catalyst for
when the known complex [RuCl
dap) and NaBArF (sodium tetrakis[3,5-bis(trifluoromethyl)phe-
nyl]borate) were stirred at room temperature for one hour in CH
2 3 3
(PPh ) ], 2,6-diacetylpyridine
the title reaction, and initial screening efforts for a test reaction
between phenyl acetylene and benzoic acid are compiled in Table 1.
As can be seen, the reaction is dependent on the reaction temper-
ature, the solvent, potential additives, and the reaction time.
Toluene was found to be the solvent of choice (Table 1, entry 1).
Lower reaction times and temperatures resulted in lower yields
or no conversion (entries 2–4), and 18 h at 85 °C gave the highest
yield. It has been reported that bases as additive can improve the
(
2
-
+
À
Cl
isolated from the reaction mixture in 92% yield (Scheme 2), which
will be referred to subsequently as [RuCl(dap)(PPh ]BArF. The
new complex was characterized by multinuclear NMR, IR, MS
2 3 2
, the deep purple complex [RuCl(dap)(PPh ) ] BArF could be
3 2
)
3
1
1
and microanalysis. The P{ H} NMR spectrum showed two mutu-
ally coupled doublets, demonstrating the presence of two magnet-
6
yield and/or the selectivity of the enol ester formation. However,
for our catalyst, it appeared that bases such as DBU, Et N, Na CO
3 2 3
3
ically inequivalent PPh ligands.
In order to unequivocally establish the structure of the complex,
its X-ray structure was determined. The molecular structure is
depicted in Fig. 1, and key bond lengths and angles are given in
the Figure caption. Additional details for the structure determina-
tion are given in the Supplementary data.
or NaHCO completely shut down the reaction (entries 6–9), which
we tentatively ascribed to deactivation of the cationic catalyst by
3
the bases. Solvents other than toluene gave significantly lower
yields (entries 10–14). As expected, without catalyst no reaction
took place (entry 5). For optimum results, the alkyne was
employed in a twofold excess over the carboxylic acid substrate.
Catalyst loadings as low as 1% were found to be sufficient. In all
cases, the Markovnikov product was the major or the only product.
Under the optimized reaction conditions, we employed the cat-
alyst in the synthesis of a number of enol esters and the results are
compiled in Table 2. As can be seen, both aromatic and aliphatic
carboxylic acids as well as both aromatic and aliphatic alkynes
can be employed in the reaction in any combination. The reaction
also proceeds when hydroxy acids were employed as substrates
(entries 6 and 7). The products were isolated chromatographically
As can be seen from the bond angles Fig. 1, the complex
assumes a distorted octahedral architecture. The X-ray structure
Scheme 2. Synthesis of the ruthenium complex.
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M.J. Stark et al. / Tetrahedron Letters xxx (2018) xxx–xxx
3
Table 1
Optimization Experiments.
Entry
Solvent
Temperature (°C)
Catalyst (mol%)
Additive
Yield (%)
1
2
3
4
5
6
7
8
9
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
85
80
65
45
85
85
85
85
85
85
70
70
70
70
1
5
5
5
none
1
1
1
1
1
5
5
5
none
none
none
none
none
DBU
85
61
65
0
0
0
0
0
0
57
11
9
4
11
Et
Na
3
N
2
CO
3
ethyl acetate
ethyl acetate
EtOH
NaHCO
none
none
none
none
none
3
10
11
12
13
14
ClCH
THF
2
CH
2
Cl
3
CH NO
2
5
General conditions: Carboxylic acid (0.57 mmol), alkyne (1.14 mmol), and Ru (1–5 mol%) at the specified temperature for 12–18 h. All products were isolated by silica gel
chromatography and isolated yields are given.
Table 2
Isolated Yields.
Entry
1
R
1
/R
2
Product
Yield (%)
Ph/Ph
85a
b
5
7
2
3
4
3-chloro-phenyl/Ph
2-bromo-phenyl/Ph
4-methyl-3-nitro-phenyl/Ph
83a
91a
70a
b
7
9
5
6
Ph/n-Bu
70a
89a
2-hydroxyphenyl/n-Bu
7
8
2-hydroxy-2-propyl/n-Bu
74b
93b
CH
2
3
Cl/Ph
/Ph
9
CH
52a
b
2
4
1
0
Ph
2
CH/Ph
81a
(
continued on next page)
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4
M.J. Stark et al. / Tetrahedron Letters xxx (2018) xxx–xxx
Table 2 (continued)
Entry
R
1
/R
2
Product
Yield (%)
74a
1
1
Ph
2
CH/n-Bu
1
2
3-chlorophenyl/C(CH
)
3 3
72a
General conditions: Carboxylic acid (0.57 mmol), alkyne (1.14 mmol), and Ru (1 mol%) for 16 h at 85 °C. All products were isolated by silica gel chromatography and isolated
yields are given.
a
Toluene.
Ethyl acetate.
b
in 93 to 52% yields. With one exception (entry 4), toluene appears
to be the solvent of choice, as ethyl acetate gave lower isolated
yields in entries 1 and 9, as expected from the screening experi-
ments in Table 1. While ethyl acetate was not as good of a solvent
as toluene, it was an acceptable solvent for some cases, where the
carboxylic acids were better soluble in ethyl acetate as compared
to toluene. Yields and selectivities compare well with other ruthe-
nium catalysts for the reaction, and the reaction conditions are
Markovnikov product was still the major one, however. Both the
(E) and (Z) isomers of the anti-Markovnikov products were
detected in the reaction mixtures, with a slight excess of the (Z)
over the (E) isomer.
The selectivity of the ruthenium catalyst to generate the Mar-
kovnikov product and the selectivities in Table 3 can, in part, be
explained based on steric considerations. It has been suggested
2
that coordination of the alkyne in an
g
-fashion (species A in
comparable. Advantages of the [RuCl(dap)(PPh
are the low catalyst loading of only 1% and, more significantly,
no additives are required.
3
)
2
]BArF catalyst
Fig. 2) gives nucleophilic attack at the Cb carbon of the alkyne to
afford the Markovnikov product, while the isomeric vinylidene
species B (Fig. 2) gives the anti-Markovnikov products through
All reactions in Table 2 afforded the geminal enol esters as the
major products resulting from Markovnikov addition to the alkyne.
The products in entries 3, 4, 6, 7, 10 and 11 were isolated as a single
isomer, and at most trace quantities of the other isomers were
detected by NMR. The other products were isolated with detect-
able amounts of the other isomers, which were, like the major iso-
nucleophilic attack at the Ca carbon. The electronic and steric fac-
tors that lead to either Markovnikov or anti-Markovnikov addition
8
are not very well understood. However, as can be seen in Table 3,
for the present catalyst system, the anti-Markovnikov product
forms with either a small carboxylic acid (acetic acid) or with a
sterically demanding alkyne (3,3-dimethylbut-1-yne). A sterically
demanding alkyne might exhibit some tendency to form the vinyli-
dene species B and a small carboxylic acid might favor the attack of
mer, identified based on the coupling constants of the alkene
protons, as performed previously by others.4
e,13
As can be seen in
Table 3, the products in entries 1, 2, and 5 contain only 4 to 5%
of the other two isomers. However, the products in entries 9 and
the
anti-Markovnikov product. In general, the complex [RuCl(dap)
(PPh ]BArF can be tuned sterically through the acyl units and
a carbon atom in B, giving rise to the formation of some of the
1
2 of Table 3 contained 17 to 24% of the other isomers. The
3 2
)
Table 3
Regioselectivity of Selected Products as Determined by 1H NMR.
Entry
1
Major product
Isolated yield (%)
88
gem: (Z): (E) % selectivitya
96:2:2
2
5
9
87
74
70
79
94:4:2
95:3:2
74:14:12
75:15:10
1
2
General conditions: Carboxylic acid (0.57 mmol), alkyne (1.14 mmol), and [Ru] (1 mol%) for 16 h at 85 °C in toluene. All products were isolated by silica gel chromatography.
a
The ratio of constitutional isomers was determined by the ratio of discrete peaks in the 1H NMR.
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M.J. Stark et al. / Tetrahedron Letters xxx (2018) xxx–xxx
5
References
1.
2.
3.
Chinchilla R, Nájera C. Chem Soc Rev. 2011;40:5084–5121.
Yi CS. J Organomet Chem. 2011;696:76–80.
(a) Rotem M, Shvo Y. Organometallics. 1983;2:1689–1691;
(
b) Rotem M, Shvo Y. J Organomet Chem. 1993;448:189–204.
4.
(a) Jeschke J, Gäbler C, Lang H. J Org Chem. 2016;81:476–484;
(
(
b) Nicks F, Libert L, Delaude L, Demonceau A. Aust J Chem. 2009;62:227–231;
c) Neveux M, Seiller B, Hagedorn F, Bruneau C, Dixneuf PH. J Organomet Chem.
1
(
(
993;451:133–138;
d) Cadierno V, Francos J, Gimeno J. Organometallics. 2011;30:852–862;
e) Mitsudo T-a, Hori Y, Yamakawa Y, Watanabe Y. Org Chem.
987;52:2230–2239.
(a) Wei S, Pedroni J, Meißner A, et al. Chem Eur J. 2013;19:12067–12076;
b) Karabulut S, Özgün Öztürk B, Imamo g˘ lu Y.
Organomet Chem.
010;695:2161–2166;
c) Nishiumi M, Miura H, Wada K, Hosokawa S, Inoue M. Adv Synth Catal.
010;352:3045–3052;
J
1
5.
(
2
(
2
J
(
(
(
(
d) Lumbroso A, Vautravers NR, Breit B. Org Lett. 2010;12:5498–5501;
e) De Clercq B, Verpoort F. J Organomet Chem. 2003;672:11–16;
f) De Clercq B, Verpoort F. Tetrahedron Lett. 2001;42:8959–8963;
Fig. 2. Potential intermediates.
g) Doucet H, Martin-Vaca B, Bruneau C, Dixneuf PH.
995;60:7247–7255.
Goossen LJ, Paetzold J, Koley D. Chem Commun. 2003;706–707.
J Org Chem.
1
6.
electronically through the pyridyl ring system. Thus, the complex
can be modified to better understand the steric and electronic fac-
tors that determine the selectivity of the title reaction.
7. Yi CS, Gao R. Organometallics. 2009;28:6585–6592.
8
9
.
.
Tan ST, Fan WY. Eur J Inorg Chem. 2010;4631–4635.
(a) González-Liste PJ, García-Garrido SE, Cadierno V. Org Biomol Chem.
017;15:1670–1679;
2
(
(
b) Jeschke J, Engelhardt TB, Lang H. Eur J Org Chem. 2016;1548–1554;
c) Huang H, Zhang X, Yu C, Li X, Zhang Y, Wang W. ACS Catal.
2
(
016;6:8030–8035;
d) Kawatsura M, Namioka J, Kajita K, Yamamoto M, Tsuji H, Itoh T. Org Lett.
011;13:3285–3287.
10. (a) Kamigaito M, Satoh K. Macromolecules. 2008;41:269–276;
b) Baskaran D. Prog Polym Sci. 2003;28:521–581.
1. (a) Berkessel A, Sebastian-Ibarz ML, Müller TN. Angew Chem Int Ed.
006;45:6567–6570;
Conclusion
2
In conclusion, we have synthesized a ruthenium complex of the
formula [RuCl(dap)(PPh ) ]BArF as a tunable catalyst for the atom-
3 2
economic Markovnikov addition of carboxylic acid to terminal
alkynes to afford enol esters in 93 to 52% isolated yields. The cata-
lyst does not require any additives and in the majority of the cases,
at best trace amounts of other isomers were detected in the iso-
(
1
2
(b) Uemura M, Nishimura H, Yamada S, Nakamura K, Hayashia Y. Tetrahedron
Lett. 1993;34:6581–6582.
12. (a) Kleman P, Pizzano A. Tetrahedron Lett. 2015;56:6944–6963;
(
b) Abrams ML, Foarta F, Landis CR. J Am Chem Soc. 2014;136:14583–14588.
3 2
lated products. The complex [RuCl(dap)(PPh ) ]BArF constitutes a
13. Poladura B, Martínez-Castañeda Á, Rodríguez-Solla H, Llavona R, Concellón C,
del Amo V. Org Lett. 2013;15:2810–2813.
tunable platform as catalyst for the title reaction and allows for
future investigation of steric an electronic factors on the selectivity
of the title reaction.
1
1
4. Huang F, Quach TD, Batey RA. Org Lett. 2013;15:3150–3153.
5. (a) Reviews and representative examples: Sears JM, Lee W-C, Frost BJ. Inorg
Chim Acta. 2015;431:248–257;
(
2
b) Thirunavukkarasu VS, Kozhushkov SI, Ackermann L. Chem Commun.
014;50:29–39;
(
(
c) Kumar P, Gupta RK, Pandey DS. Chem Soc Rev. 2014;43:707–733;
d) García-Álvarez R, Díaz-Álvarez AE, Crochet P, Cadierno V. RSC Adv.
Acknowledgments
2
013;3:5889–5894;
We would like to thank the National Science Foundation (NSF
CHE-1300818) for financial support. Further funding from the
National Science Foundation for the purchase of the NMR spec-
trometer (CHE-9974801), the purchase of the ApexII diffractometer
(e) Carmona D, Viguri F, Pilar Lamata M, et al. Dalton Trans.
2012;41:10298–10308;
(
f) Milde B, Rüffer T, Lang H. Inorg Chim Acta. 2012;387:338–345;
g) Hiett NP, Lynam JM, Welby CE, Whitwood AC. Organomet Chem.
011;696:378–387.
16. (a) Carmona D, Lamata MP, Pardo P, et al. Organometallics. 2014;33:616–619;
b) Faller J, Parr J. Curr Org Chem. 2006;10:151–163.
7. (a) Stark MJ, Shaw MJ, Fadamin A, Rath NP, Bauer EB. J Organomet Chem.
017;847:41–53;
(b) Stark MJ, Shaw MJ, Rath NP, Bauer EB. Eur J Inorg Chem. 2016;1093–1102;
(
2
J
(
(
MRI, CHE-0420497) and the purchase of the mass spectrometer
CHE-9708640) is acknowledged. Matthew Stark gratefully
(
1
acknowledges a dissertation fellowship awarded by the Graduate
School of the University of Missouri – St. Louis. We would like to
thank Evan Stephenson and Yechezkel Brown for assistance with
data collection.
2
(
(
(
(
c) Alkhaleeli DF, Baum KJ, Rabus JM, Bauer EB. Catal Commun. 2014;47:45–48;
d) Widaman AK, Rath NP, Bauer EB. New J Chem. 2011;35:2427–2434;
e) Costin S, Rath NP, Bauer EB. Inorg Chem Commun. 2011;478–480;
f) Costin S, Widaman AK, Rath NP, Bauer EB. Eur
011;1269–1282;
J Inorg Chem.
2
(g) Costin S, Rath NP, Bauer EB. Tetrahedron Lett. 2009;50:5485–5488;
(h) Costin S, Sedinkin SL, Bauer EB. Tetrahedron Lett. 2009;50:922–925;
(i) Costin S, Rath NP, Bauer EB. Inorg Chim Acta. 2009;361:1935–1942;
A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at https://doi.org/10.1016/j.tetlet.2018.01.029.
(j) Costin S, Rath NP, Bauer EB. Adv Synth Catal. 2008;350:2414–2424.
Please cite this article in press as: Stark M.J., et al. Tetrahedron Lett. (2018), https://doi.org/10.1016/j.tetlet.2018.01.029