Photoredox catalysis of intramolecular cyclizations with a reusable silica-bound ruthenium complex

Article abstract of DOI:10.1002/cctc.201500304

Photoredox catalysis with the use of a stable, reusable silica-bound chromophore was applied to the intramolecular cyclization of a series of 2-benzylidenehydrazinecarbothioamides to give 5-phenyl-1,3,4-thiadiazol-2-amines. The catalyst was readily prepar

Full text of DOI:10.1002/cctc.201500304

DOI: 10.1002/cctc.201500304
Communications
Photoredox Catalysis of Intramolecular Cyclizations with
a Reusable Silica-Bound Ruthenium Complex
[
a]
[a]
[a]
[a]
Gregory J. Barbante,* Trent D. Ashton, Egan H. Doeven, Frederick M. Pfeffer, David
[c]
[a, b]
[a]
J. D. Wilson, Luke C. Henderson,
and Paul S. Francis*
Photoredox catalysis with the use of a stable, reusable silica-
bound chromophore was applied to the intramolecular cycliza-
tion of a series of 2-benzylidenehydrazinecarbothioamides to
give 5-phenyl-1,3,4-thiadiazol-2-amines. The catalyst was
readily prepared by carbodiimide-mediated coupling of com-
mercially available amine-functionalized silica beads to a car-
boxylic acid functionalized ruthenium complex. The immobi-
lized catalyst was readily removed from the reaction product
by filtration and was used eight times without loss of catalytic
activity. This simple, safe, and practical method is an attractive
alternative to conventional procedures.
In this example, the polymer catalyst could be used at least
four times without significant loss of activity. However, the
methods by which these immobilized catalysts are prepared
can sometimes be tedious, and hence, their widespread adop-
[2c]
tion by the chemistry community has been slow.
With this in mind, we sought to identify a simple process to
II
covalently immobilize Ru polypyridyl complexes onto a silica
platform to create stable, reusable photoredox catalysts for or-
ganic transformations. Ruthenium polypyridyl derivatives have
previously been anchored to mesoporous silica for chemilumi-
[5]
[6]
nescence detection and photocatalytic hydrogen evolution,
but the synthetic pathways for preparing the immobilized
complex were nontrivial, as they proceeded through multistep
protocols involving silane derivatives of the bipyridine ligands.
A more amenable synthetic approach has been devised by
Light is an abundant and renewable resource in nature, and re-
searchers have long sought to exploit its energy for chemical
[
1]
[7]
transformations. Many organic molecules cannot absorb visi-
Papafotiou and co-workers, who attached a biomimetic [Ru-
2
+
ble light efficiently, but photocatalysts such as [Ru(bpy)3]
bpy=2,2’-bipyridine) have been shown to drive the formation
of new chemical bonds (CÀC and CÀhetero) for a wide range
of organic transformations.
(terpy)(bpy) ](Cl)2 (terpy=2,2’;6’,2“-terpyridine) complex to
2
(
silica by aminopropyl functionalization of the silica surface,
then amide coupling to a bipyridine carboxylic acid, and finally
complexation with the ruthenium species. Herein, we report
the most efficient route to date: a two-step process involving
the direct immobilization of a carboxylic acid functionalized
ruthenium(II) polypyridyl derivative onto a commercially avail-
able silica (SiliaBond Amine) to create a convenient, stable, and
reusable photoredox catalyst (i.e., 1) for organic transforma-
tions.
[
2]
To date, most visible-light-promoted photoredox catalysts
are designed for homogenous use and the rare-earth-metal
catalyst is unfortunately discarded during purification of the
desired product. However, some heterogeneous CdS and TiO
2
[
3]
materials and metal–organic frameworks or organic polymers
[
4]
incorporating metal-complex chromophores have recently
[
4h]
been reported. Yoo and Kobayashi, for example, described
an immobilized iridium-based catalyst for the aerobic phos-
phonylation of N-aryltetrahydroisoquinones under visible light.
As proof of concept, we used the photoredox catalyst for in-
tramolecular cyclizations of 2-benzylidenehydrazinecarbothio-
amides 2 to give 5-aryl-1,3,4-thiadiazol-2-amines 3 (Scheme 1).
These and similar classes of heterocyclic molecules have re-
ceived considerable attention owing to their wide range
[a] Dr. G. J. Barbante, Dr. T. D. Ashton, Dr. E. H. Doeven, Dr. F. M. Pfeffer,
Dr. L. C. Henderson, Dr. P. S. Francis
Centre for Chemistry and Biotechnology
School of Life and Environmental Sciences
Deakin University
Locked Bag 20000, Geelong, Victoria 3220 (Australia)
E-mail: paul.francis@deakin.edu.au
gregbarbante@msn.com
[b] Dr. L. C. Henderson
Institute for Frontier Materials
Deakin University
Locked Bag 20000, Geelong, Victoria 3220 (Australia)
[
c] Dr. D. J. D. Wilson
Department of Chemistry and Physics
La Trobe Institute for Molecular Science
La Trobe University
Melbourne 3086 (Australia)
Supporting Information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201500304.
Scheme 1. Photocatalytic reaction of 2-benzylidenehydrazinecarbothio-
amides to give 5-phenyl-1,3,4-thiadiazol-2-amines.
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[
8]
of pharmacological activity.
Whereas photoredox ap-
proaches have been outlined by
Table 1. Optimization of the reaction conditions.
[
9]
Li and co-workers for the cycli-
zation of thioanilides to form
the related 2-arylbenzothiazoles
[
10]
[
a]
and by Yadav and Yadav for
the cyclization of acylhydra-
zones to form 1,3,4-oxadiazoles,
these reactions were all per-
formed under homogenous con-
ditions. Herein, we report a read-
ily prepared immobilized photo-
catalyst and its use to cyclize
the more challenging amino-
Entry
Light source
Catalyst
Conversion [%]
(Yield [%])
[b]
[c]
1
2
3
4
5
6
7
8
9
white light
dark
white light
white light
no catalyst
N.R.
N.R.
<10
[Ru(bpy)
[Ru(bpy)
[Ru(bpy)
[Ru(bpy)
[Ru(bpy)
[Ru(bpy)
1
3
3
3
3
3
3
](PF
](PF
](PF
](PF
](PF
](PF
6
)
6
)
6
)
6
)
6
)
6
)
2
2
2
2
2
2
[
[
c]
c]
[e]
[e]
<10
69 (63 )
(20 )
[d]
[f]
blue LED
blue LED
blue LED
blue LED
blue LED
[d]
[f]
[d]
[d]
[d]
(under N
2
)
N.R.
72 (65 )
[f]
1 (under N
2
)
N.R.
functionalized
hydrazinecarbothioamide sub-
strates to form family of
-substituted-1,3,4-thiadiazol-2-
2-benzylidene-
[
(
[
a] Unless otherwise specified, a catalyst loading of 1 mol% was used. [b] Determined by HPLC. [c] A desk lamp
Nelson, 15 W) was used as the white-light source. N.R.=no reaction. [d] l=460–465 nm. [e] Catalyst: 5 mol%.
a
f] Yield of isolated product obtained after column chromatography. Substrate 2a was synthesized according
5
[12]
to a literature procedure.
amines with a range of inbuilt
functional groups available for
further reactions.
As this was the first application of photoredox catalysis for
the preparation of phenylthiadiazolamines, we initially per-
formed the reaction with substrate 2a and [Ru(bpy) ](PF )
4-butanoic acid} was synthesized by using well-established
[13]
chemistry.
Heterogeneous photocatalyst
1
(Table 1, entry 8) gave
3
6 2
under homogeneous conditions (Table 1). No reaction was ob-
served in the absence of the catalyst (Table 1, entry 1) or in the
presence of catalyst without light (Table 1, entry 2). The use of
a standard white-light bulb as the initiator with a catalyst load-
ing of 1 mol% gave only poor conversion over 24 h (Table 1,
entry 3), and this yield was not significantly improved by in-
creasing the catalyst loading to 5 mol% (Table 1, entry 4). The
use of a monochromatic light-emitting diode (LED, 460–
a yield of phenylthiadiazolamine 3a similar to that obtained in
the analogous homogeneous reaction (Table 1, entry 5) over
the same timeframe. However, unlike [Ru(bpy) ](PF ) , immobi-
3
6 2
lized catalyst 1 was conveniently collected from the product
solution by means of vacuum filtration. After removal of the re-
action solvent, the product was readily precipitated from
water/ethanol in yields >50% (i.e., time-consuming column
chromatography was no longer essential). We found that the
catalyst collected in this simple manner could be used at least
eight times for the intramolecular cyclization reaction with
negligible loss of catalytic activity (Figure 1).
4
65 nm) with the catalyst (1 mol%) gave a much improved
yield, and the complete consumption of 2a was noted within
h (Table 1, entry 5). These mild, room-temperature conditions
3
[9]
are superior to those involved in conventional protocols to
Li and co-workers found that the presence of low levels of
O2 was critical for a successful photocatalyzed reaction. We
access compounds such as 3a, which typically involve elevated
[8c,11]
temperatures and FeCl as a catalyst or acid chlorides.
In
3
an attempt to improve the reaction yield, the [Ru(bpy) ](PF )
3
6 2
catalyst loading was increased to 5 mol%, but this resulted in
precipitation of the catalyst together with the product as an
opaque film in the reaction vessel, and no rate enhancement
was observed (Table 1, entry 6).
The inorganic base K CO has been used in similar photo-
2
3
[
9]
catalytic reactions. However, in the cyclization performed
herein, only a trace amount of the product was formed, even if
a large excess amount of this base was used.
Next, the heterogeneous reaction performed with the use of
photocatalyst 1 was examined. The immobilized catalyst was
easily prepared from two commercially available materials:
aminopropyl-functionalized silica beads and the carboxylic acid
2
+
derivative of [Ru(bpy)3] . A readily performed 1-ethyl-3-(3-di-
methylaminopropyl)carbodiimide (EDCI)-mediated amide cou-
pling gave the complete catalyst. Despite being commercially
available, to minimize cost the carboxylic acid derivative {i.e.,
Figure 1. Product yields (using simple purification from ethanol/water solu-
tion) for the formation of 3a upon recycling catalyst 1. Prior to final purifica-
tion, each filtered product solution was analyzed by photoluminescence and
no emission at l=620 nm (characteristic of the Ru complex luminophore)
was observed. Moreover, there was no change in the color of the catalyst
with repeated use.
II
[
Ru(bpy) (mba-bpy)](PF ) , mba-bpy=4’-methyl-2,2’-bipyridine-
2 6 2
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therefore examined our homogeneous and heterogeneous
photocatalytic syntheses of phenylthiadiazolamines in the ab-
Considering the critical dependence of these cyclization re-
actions on the photocatalyst, DBU, and O , a mechanism has
2
[9]
sence of oxygen (i.e., under an atmosphere of N ; Table 1, en-
been proposed involving 5-endo-trig cyclization. First, the
Schiff base is deprotonated to form the thiolate anion. Oxida-
tion to the thiol radical is accomplished by the strong oxidant
2
tries 7 and 9) and no conversion to the desired product was
observed. Indeed, optimum yields were obtained if the reac-
tions were conducted with the reaction vessel open to the at-
mosphere.
3
+
[Ru(bpy)3] (or its immobilized analogue, Scheme 2) which is
To examine the scope of the reaction, a range of
suitable substituted 2-benzylidenehydrazinecarbo-
thioamides were subject to the reaction by using
catalyst 1. Most functional groups were well tolerat-
ed and gave clean conversions within 4–6 h to the
cyclized products (Table 2), which included
a number of novel products. Substrates with an un-
substituted (e.g., compound 2b) or electron-defi-
cient 4-fluoro- (e.g., compound 2a) or 3,4-dichloro-
(
e.g., compound 2c) substituted phenyl ring were
cyclized in good yields of 65%. Moderate yields of
9–62% were obtained for substrates containing
3
various other electron-donating and electron-with-
drawing phenyl substituents (e.g., compounds 2d–
g). Low yields were obtained for the substrate with
a 4-nitrophenyl substituent (e.g., compound 2h).
Upon adding 1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU) to the reaction mixture containing 2h, the so-
Scheme 2. Mechanism for the formation of 1,3,4-thioadiazoles.
lution went dark brown, possibly reducing the quan-
tity of light arriving at the catalyst. Attempts to cy-
II
clize substrates 2i–k were not successful. Compounds 2 f and
j were not soluble in neat MeCN; thus, DMF and 30% DMF in
generated in situ upon quenching of the excited Ru species
2
by O . Formation of the thiol radical in turn regenerates the
2
II
MeCN were used, respectively.
Ru catalyst. The radical intramolecularly attacks the C=N bond
in a 5-endo-trig cyclization to form intermediate IV. A hydrogen
·
À
atom is lost to O2 and IV regains aromaticity to give the de-
sired product. Although a 5-endo-trig reaction is not favored
by Baldwin’s rules, exceptions involving small heterocyclic
Table 2. Scope of the reaction by using the immobilized photocatalyst.
[14]
S-containing species are known.
DFT calculations support the proposed mechanism and ex-
perimental observations. The proton affinities of 2b–h, 2j, and
À1
2
l are high (654–670 kJmol in MeCN solvent), which thus re-
À1
quires a strong base such as DBU (712 kJmol in MeCN) to
ensure proton abstraction in the initial step (Scheme 2). The
calculated oxidation of II by itself is endergonic by 450–
À1
2+
3+
4
74 kJmol , but inclusion of [Ru(bpy)3] /[Ru(bpy)3]
À1
(
À510 kJmol ) makes this step favorable. Similarly, conversion
À1
of III into IV is unfavorable by approximately 100 kJmol with-
À
À
2
À1
out the inclusion of O /HO (À216 kJmol ) in the calcula-
2
tion. Rearrangement of III into IV is exergonic, with calculated
À1
barriers of only 12–20 kJmol . The calculations support the
observed dependence on the presence of the Ru photocata-
lyst, O , and strong base; O is important both for the oxida-
2
2
3
+
tion of II (O is required to produce [Ru(bpy) ] in the Ru
2
3
redox cycle) and in the final step to remove a H atom from IV
À
(
as the O2 byproduct from the Ru redox cycle).
In conclusion, the utility of a readily prepared heterogene-
ous photoredox catalysis as a mild and selective method for
radical initiation in the intramolecular cyclization of 5-aryl-
[
a] Reaction was performed in 30% DMF in MeCN. [b] Reaction was per-
1,3,4-thiadiazol-2-amines was demonstrated. The method is
formed in DMF.
characterized by low catalyst loadings and simple reaction
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design, and this enabled a wide range of 1,3,4-thiadiazoles to
be readily accessed. The catalyst was exceedingly simple to
prepare by using commercially available amine-functionalized
silica. The immobilized catalyst was readily isolated from the
reaction product by filtration and was used eight times with
no loss in catalytic activity. This safe and practical method is an
attractive choice if mild reaction conditions are required.
tion of XPS data and Dr. Thomas Gengenbach for helpful discus-
sions. We also thank La Trobe University, NCI-NF and VPAC for
computing resources.
Keywords: heterogeneous catalysis
·
photocatalysis
·
ruthenium · thiadiazolamines · visible light
[
[
1] H. D. Roth, Angew. Chem. Int. Ed. Engl. 1989, 28, 1193–1207; Angew.
Chem. 1989, 101, 1220–1234.
2] a) D. A. Nicewicz, D. W. C. MacMillan, Science 2008, 322, 77–80; b) K.
Zeitler, Angew. Chem. Int. Ed. 2009, 48, 9785–9789; Angew. Chem. 2009,
Experimental Section
Preparation of heterogeneous catalyst 1
1
21, 9969–9974; c) T. P. Yoon, M. A. Ischay, J. Du, Nat. Chem. 2010, 2,
The ruthenium complex {[Ru(bpy) (mba-bpy)](PF ) } was prepared
as previously described. The complex (0.01 g, 0.01 mmol), EDCI
2
6 2
[13]
527–532; d) J. M. R. Narayanam, C. R. J. Stephenson, Chem. Soc. Rev.
2
2
7
Angew. Chem. 2012, 124, 6934–6944; h) C. K. Prier, D. A. Rankic, D. W. C.
MacMillan, Chem. Rev. 2013, 113, 5322–5363; i) Y. Xi, H. Yi, A. Lei, Org.
Biomol. Chem. 2013, 11, 2387–2403; j) J. Xie, H. Jin, P. Xu, C. Zhu, Tetra-
hedron Lett. 2014, 55, 36–48.
011, 40, 102–113; e) J. W. Tucker, C. R. J. Stephenson, J. Org. Chem.
012, 77, 1617–1622; f) L. Shi, W. Xia, Chem. Soc. Rev. 2012, 41, 7687–
697; g) J. Xuan, W.-J. Xiao, Angew. Chem. Int. Ed. 2012, 51, 6828–6838;
(
1 equiv.), and DMAP (0.3 equiv.) were dissolved in dichlorome-
À1
thane (10 mL). Predried SiliaBondAmine (0.1 g, 1.91 mmolg ; 40–
6
3 mm 60 A, Silicycle, Inc., Canada, www.silcycle.com) was added to
this solution, and the mixture was heated at reflux for 24 h under
a nitrogen atmosphere. The red product was filtered in a sintered
funnel; washed with dichloromethane, ethanol, methanol, and
aqueous 2m HCl; treated with saturated KPF ; and washed with
[3] a) T. Mitkina, C. Stanglmair, W. Setzer, M. Gruber, H. Kisch, B. Koenig,
Org. Biomol. Chem. 2012, 10, 3556–3561; b) M. Rueping, J. Zoller, D. C.
Fabry, K. Poscharny, R. M. Koenigs, T. E. Weirich, J. Mayer, Chem. Eur. J.
6
distilled water and finally acetone. The derivatized silica was then
dried in vacuo at 708C overnight to give a bright orange granule
powder (0.0033 mmol/100 mg). Control experiments with [Ru-
2
012, 18, 3478–3481.
4] a) Z. Xie, C. Wang, K. E. deKrafft, W. Lin, J. Am. Chem. Soc. 2011, 133,
056–2059; b) H. Shimakoshi, M. Nishi, A. Tanaka, K. Chikama, Y. Hisae-
[
(
bpy) ](PF ) in the coupling step showed no attachment, as it was
3 6 2
2
consequently washed out of the SiliabondAmine in the filtration
step. Analysis by X-ray photoelectron spectroscopy and compari-
son of the as-received silica particles and the surface-grated mate-
rial was consistent with successful ruthenium catalyst grafting.
da, Chem. Commun. 2011, 47, 6548–6550; c) C. Wang, Z. Xie, K. E. deK-
rafft, W. Lin, J. Am. Chem. Soc. 2011, 133, 13445–13454; d) C. Wang,
K. E. deKrafft, W. Lin, J. Am. Chem. Soc. 2012, 134, 7211–7214; e) C.
Wang, Z. Xie, K. E. deKrafft, W. Lin, ACS Appl. Mater. Interfaces 2012, 4,
2288–2294; f) J.-L. Wang, C. Wang, K. E. deKrafft, W. Lin, ACS Catal.
2
012, 2, 417–424; g) N. Priyadarshani, Y. Liang, J. Suriboot, H. S. Bazzi,
Heterogeneous reaction conditions
D. E. Bergbreiter, ACS Macro Lett. 2013, 2, 571–574; h) W.-J. Yoo, S. Ko-
bayashi, Green Chem. 2014, 16, 2438–2442.
A mixture of benzylidenehydrazinecarbothioamide (0.5 mmol), cat-
alyst 1 (0.005 mmol, 1 mol%), and DBU (0.5 mmol, 1 equiv.) in
MeCN (5 mL, unless stated otherwise) was placed at a distance of
approximately 5 cm from a 10 W blue LED and was stirred at room
temperature. Reactions were typically run for 4 h, at which point
the LEDs were powered off. MeCN (5 mL) was added, and the mix-
ture was sonicated (5 min). The mixture was filtered on a sintered
funnel to remove the catalyst, and MeCN was removed under re-
duced pressure. The residue was diluted in ethanol (2 mL), cooled
in ice, and water was added to give the desired 5-phenyl-1,3,4-thia-
diazole-2-amine. The homogeneous reaction conditions are includ-
ed in the Supporting Information.
[5] a) N. W. Barnett, R. Bos, H. Brand, P. Jones, K. F. Lim, S. D. Purcell, R. A.
Russell, Analyst 2002, 127, 455–458; b) G. M. Greenway, A. Greenwood,
P. Watts, C. Wiles, Chem. Commun. 2006, 85–87.
[
6] M. Waki, Y. Maegawa, K. Hara, Y. Goto, S. Shirai, Y. Yamada, N. Mizoshita,
T. Tani, W.-J. Chun, S. Muratsugu, M. Tada, A. Fukuoka, S. Inagaki, J. Am.
Chem. Soc. 2014, 136, 4003–4011.
[
[
7] F. Papafotiou, K. Karidi, A. Garoufis, M. Louloudi, Polyhedron 2013, 52,
634–638.
8] a) S. Ferrari, F. Morandi, D. Motiejunas, E. Nerini, S. Henrich, R. Luciani, A.
Venturelli, S. Lazzari, S. Calò, S. Gupta, V. Hannaert, P. A. M. Michels, R. C.
Wade, M. P. Costi, J. Med. Chem. 2011, 54, 211 –221; b) M. S. Alam, L. Liu,
D. U. Lee, Chem. Pharm. Bull. 2011, 59, 1413–1416; c) S. G. Alegaon,
K. R. Alagawadi, Med. Chem. Res. 2012, 21, 816–824.
[
9] Y. Cheng, J. Yang, Y. Qu, P. Li, Org. Lett. 2012, 14, 98–101.
[
[
10] A. K. Yadav, L. D. S. Yadav, Tetrahedron Lett. 2014, 55, 2065–2069.
11] a) I. KüÅükgüzel, G. Satilmis, K. R. Gurukumar, A. Basu, E. Tatar, D. B. Nich-
ols, T. T. Talele, N. Kaushik-Basu, Eur. J. Med. Chem. 2013, 69, 931–941;
b) N.-H. Nam, T. L. Huong, D. T. M. Dung, P. T. P. Dung, D. T. K. Oanh, S. H.
Park, K. Kim, B. W. Han, J. Yun, J. S. Kang, Y. Kim, S.-B. Han, J. Enzyme
Inhib. Med. Chem. 2014, 29, 611 –618.
Catalyst regeneration
Catalyst 1 was suspended in ethanol, sonicated (5 min), and fil-
tered on a sintered funnel. The catalyst was further washed with
2
m HCl (2”5 mL) and distilled water and treated with a saturated
[
[
[
12] W. Yi, C. Dubois, S. Yahiaoui, R. Haudecoeur, C. Belle, H. Song, R. Hardre,
M. Reglier, A. Boumendjel, Eur. J. Med. Chem. 2011, 46, 4330–4335.
13] G. J. Barbante, C. F. Hogan, D. J. D. Wilson, N. A. Lewcenko, F. M. Pfeffer,
N. W. Barnett, P. S. Francis, Analyst 2011, 136, 1329–1338.
14] a) C. Chatgilialoglu, C. Ferreri, M. Guerra, V. Timokhin, G. Froudakis, T. Gi-
misis, J. Am. Chem. Soc. 2002, 124, 10765–10772; b) M. Journet, A.
Rouillard, D. Cai, R. D. Larsen, J. Org. Chem. 1997, 62, 8630–8631.
KPF solution to replace the counterion. A final wash with acetone
was used to remove water, and the product was left to dry
in vacuo at 608C overnight.
6
Acknowledgements
We thank the Australian Research Council for funding
Received: March 24, 2015
(FT100100646). We gratefully acknowledge CSIRO for the acquisi-
Published online on May 7, 2015
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ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim