Ruthenium-catalyzed rearrangement of propargyl sulfoxides: Formation of α,β-unsaturated thioesters

Article abstract of DOI:10.1016/j.tetlet.2014.11.138

Our previously developed strategy of generating ketene intermediates via Ru-catalyzed intramolecular oxidation of terminal alkynes is applied to propargyl sulfoxides. The reaction undergoes interesting further rearrangement upon the ketene generation to a

Full text of DOI:10.1016/j.tetlet.2014.11.138

Tetrahedron Letters xxx (2014) xxx–xxx
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Ruthenium-catalyzed rearrangement of propargyl sulfoxides:
formation of a,b-unsaturated thioesters
Renhua Zheng a,b, Youliang Wang b, Liming Zhang b,
⇑
a School of Pharmaceutical and Chemical Engineering, Taizhou University, Taizhou 318000, China
b Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Our previously developed strategy of generating ketene intermediates via Ru-catalyzed intramolecular
oxidation of terminal alkynes is applied to propargyl sulfoxides. The reaction undergoes interesting fur-
Received 17 November 2014
Revised 26 November 2014
Accepted 28 November 2014
Available online xxxx
ther rearrangement upon the ketene generation to afford
yields in the reported cases.
a,b-unsaturated thioesters in good to excellent
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Ketene
Ru vinylidene
Oxidation
Thioester
O
Introduction
R
O
NBn
Ph
NBn
Ph
S
intermolecular
[2+2]
Ruthenium vinylidenes1 are versatile intermediates in organic
synthesis and can be readily generated from terminal alkynes.
They have served as key and versatile intermediates in a diverse
range of efficient transformations.2
ArS
H
H
84%
Ar = 2,6-Me2Ph
O
[Ru]
O
R
R
•
S
S
•
[Ru]
Recently, we3 reported that in situ-generated Ru vinylidenes
can be oxidized4,5 by appropriately tethered sulfoxides to afford
ketenes.6 These synthetically versatile intermediates can be
trapped by tethered olefins or separate imines to afford cyclobuta-
nones and b-lactams, respectively (Scheme 1).
Me
S
91%
intramolecular
[2+2]
O
R
[Ru]
S
S
O
H
Me
Me
Scheme 1. The oxidation of in situ generated Ru vinylidenes into ketenes by using
During that study, we examined an aryl propargyl sulfoxide
(i.e., 1a) and discovered that besides the expected b-lactam prod-
uct 2a the thioacrylate 3a was formed as a byproduct in 5% yield
(Scheme 2). In the absence of the imine reaction partner, the yield
of 3a was improved to an unoptimized 31%. A mechanism is
proposed to rationalize its formation and entails initial oxidative
generation of the sulfide ketene A, then cyclization of the sulfide
moiety of A to its ketene part to form the zwitterionic dihydrothie-
tium species B, and finally the electrocyclic ring opening of B. Since
this side reaction offers a unique access to synthetically useful
tethered sulfoxides and examples of their trapping.
O
Bn
Ph
CpRu(PPh3)2Cl (5 mol%)
NaBArF4 (10 mol%)
L2 (10 mol%)
N
H
O
S
Bn
N
O
+
+
Ar
H
Ph
4 Å MS, DCE, 60 °C
SAr
SAr
1a
3a
5%
2a
Ar = 2,6-Me2Ph
1.2 equiv
1.0 equiv
1.0 equiv
0 equiv
62%, dr> 100:1
-
Bn
N
31%
Ph
a
,b-unsaturated thioesters, we set out to optimize the reaction
O
•
[Ru]
Ar
O
[Ru]
conditions and examine its scope. Herein we report our findings.
•
O
S
S
S
Ar
Ar
A
B
Scheme 2. Ru-catalyzed reactions of aryl propargyl sulfoxides and a proposed
mechanism for the formation of 3a.
⇑
Corresponding author. Tel.: +1 805 893 7392; fax: +1 805 893 4120.
E-mail address: zhang@chem.ucsb.edu (L. Zhang).
http://dx.doi.org/10.1016/j.tetlet.2014.11.138
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Zheng, R.; et al. Tetrahedron Lett. (2014), http://dx.doi.org/10.1016/j.tetlet.2014.11.138

2
R. Zheng et al. / Tetrahedron Letters xxx (2014) xxx–xxx
Table 1
Initial condition optimizationa
Ar
S
catalyst
Ph
O
iPr
Ph
conditions
O
N
PPh2
iPr
N
PPh2
Ph
SAr
4 Å MS
Ph
Ph
L1
iPr
L2
3b
Ar = 2,6-(Me)2Ph
1b
Entry
Catalyst
Ligand
Conditions
Yieldb (%)
1
2
3
4
CpRu(PPh3)2Cl (2%), NaBArF4 (4%)
CpRu(PPh3)2Cl (2%), NaBArF4 (4%)
CpRu(PPh3)2Cl (2%), NaBArF4 (4%)
CpRu(PPh3)2Cl (2%), NaBArF4 (4%)
CpRu(PPh3)2Cl (2%), NaPF6 (4%)
CpRu(PPh3)2Cl (2%), AgNTf2 (4%)
CpRu(PPh3)2Cl (2%), NaBArF4 (4%)
CpRu(PPh3)2Cl (2%), NaBArF4 (4%)
CpRu(PPh3)2Cl (2%), NaBArF4 (4%)
CpRu(PPh3)2Cl (2%), NaBArF4 (4%)
CpRu(PPh3)2Cl (2%), NaBArF4 (4%)
CpRu(PPh3)2Cl (0.5%), NaBArF4 (1%)
L2 (4%)
PPh3 (4%)
L1 (4%)
L2 (4%)
L2 (4%)
L2 (4%)
L2 (4%)
L2 (4%)
L2 (4%)
L2 (4%)
L2 (4%)
L2 (4%)
DCE, 60 °C, 3 h
DCE, 60 °C, 6 h
DCE, 60 °C, 3 h
DCE, 40 °C, 12 h
DCE, 60 °C, 3 h
DCE, 60 °C, 3 h
DCE, 60 °C, 3 h
Toluene, 60 °C, 3 h
PhF, 60 °C, 3 h
PhCF3, 60 °C, 3 h
DCE, 60 °C, 3 h
DCE, 60 °C, 3 h
91 (91)c
<5
82
73
76
84
65
31
44
5
6
7d
8
9
10
11e
12
80
85
61
a
Initial [1b] = 0.05 M.
b
Estimated by 1H NMR using diethyl phthalate as the internal reference.
c
d
e
Isolated yield.
4 Å MS not used.
Initial [1b] = 0.5 M.
Table 2
and the Ru catalyst. As shown in Table 1, entry 1, 2 mol % of
Formation of a,b-unsaturated thioesters
CpRu(PPh3)2Cl, 4 mol% of NaBArF4, and 4 mol % of L2 led to a highly
R1
O
CpRu(PPh3)2Cl (2 mol%)
L2
O
efficient catalysis, and the expected
a,b-unsaturated thioester
S
NaBArF4 (4mol%),
(4 mol%)
R2
product 3b was formed in an excellent 91% yield and with an
excellent E-selectivity (>20:1). The structures of L2 and its less acces-
sible homolog L1 are shown in Table 1 equation. Notably, both
ligands are members of AZARPHOS having their pyridine nitrogen
sterically shielded from coordinating to Ru7 and known to facilitate
Ru-catalyzed anti-Markovnikov hydration of terminal alkyne8 via
accelerating the isomerization of terminal alkynes into Ru vinylid-
enes.9 In the absence of L2 or by replacing it with Ph3P (entry 2) little
reaction occurred. With L1 as ligand, the reaction yield was a lower
82% (entry 3). Lowering the reaction temperature (entry 4), changing
the chloride scavenger from NaBArF4 to NaPF6 (entry 5) or AgNTf2
(entry 6), and skipping 4 Å MS (entry 7) all led to lower yields.
DCE turned out to be the optimal solvent as toluene (entry 8) and
PhF (entry 9) were much inferior and PhCF3 (entry 10) was also less
effective. While increasing the reaction concentration by 10 times
slightly impacted the reaction efficiency (entry 11), lowering the cat-
alyst loading to 0.5 mol % had a much worse impact on the yield
(entry 12).
With the optimal conditions as shown in Table 1, entry 1 in
hand, the scope of this reaction was investigated, and the results
are summarized in Table 2. With the phenethyl group of 1b
replaced by an n-pentyl group, the reaction proceeded smoothly
to afford the desired thioester 3c in 89% (entry 1). Similarly, the
methyl derivative reacted without incident, albeit with a lower
yield (entry 2). The bulky 2,6-dimethylphenyl group approved
to be optimal but not uniquely effective as a 2,6-dichlorophenyl
(entry 3) and even the parent phenyl groups (entry 4) were suit-
able groups on sulfur, leading to good yields of the corresponding
products. Interestingly, even n-butyl (entry 5) was an effective
SR1
R2
4 Å MS, DCE, 60 °C
3
1
Entry
1
Substrate
Product
Yield (%)
Me
S
Me
O
O
89
79
84
S
Me
Me
Me
Me
Me
3c
1c
Me
Me
O
O
S
2
3
S
Me
Cl
Me
Cl
3d
Me
1d
O
O
S
S
Ph
Ph
Cl
Cl
3e
Ph
1e
O
O
O
O
S
S
S
S
4
71
3f
Ph
Ph
1f
(dr, 2:1)
Me
5
6
7
83
81
82
Me
Ph
1g
3g
Me
Me
O
O
O
S
S
Me
Me
3a
3h
1a
O
S
Me
1h
Me
S
substituent on the sulfoxide, and the
a,b-unsaturated thioester
3g was formed in 83% yield. When the optimized conditions were
applied to the substrate 1a used in Scheme 2, to our surprise, the
yield was much higher (entry 6) than the originally observed 31%.
The difference is loadings of the Ru catalyst and the ligand as
higher 5% and 10% were employed in the original study, respec-
tively. Propargyl butyl sulfoxide, that is, 1h, was also a suitable
substrate, and the desired thioacrylate 3h was isolated in 82%
yield (entry 7).
Results and discussion
On the outset, we chose the aryl sulfoxide 1b as the substrate
for condition optimization. At first, we employed the conditions
used in Scheme 2 with the exception of the loading of the ligand
Please cite this article in press as: Zheng, R.; et al. Tetrahedron Lett. (2014), http://dx.doi.org/10.1016/j.tetlet.2014.11.138

R. Zheng et al. / Tetrahedron Letters xxx (2014) xxx–xxx
3
in the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.11.
138. These data include MOL files and InChiKeys of the most
important compounds described in this article.
Conclusions
In summary, we have developed an efficient ruthenium-
catalyzed transformation of propargyl sulfoxides into synthetically
References and notes
useful
a,b-unsaturated thioesters. In this reaction, a ruthenium
vinylidene intermediate generated from terminal alkyne is oxidized
by the tethered sulfoxide to generate a synthetically versatile
ketene species, which in this particular reaction is trapped by the
nascent sulfide to eventually afford the product upon rearrangement.
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Acknowledgments
We are grateful for the financial support by NSF (CHE-
1301343). R.Z. thanks the fellowship from the China Scholarship
Council.
Supplementary data
Supplementary data (copies of 1H NMR and 13C NMR spectra of
substrates and products. Experimental procedures and data for
substrates and products) associated with this article can be found,
8. Labonne, A.; Kribber, T.; Hintermann, L. Org. Lett. 2006, 8, 5853–5856.
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Please cite this article in press as: Zheng, R.; et al. Tetrahedron Lett. (2014), http://dx.doi.org/10.1016/j.tetlet.2014.11.138