1
Photocatalytic Initiation of Radical Thiol-Ene
Reactions Using Carbon-Bi
2
O
3
Nanocomposites
Viviana Maffeis,
†,‡
Ruairí O. McCourt,
§
Rita Petracca,
§
Olivier Laethem,
§
Adalberto
Camisasca,
†,‡
Paula E. Colavita
§
* Silvia Giordani
†,¶
* and Eoin M. Scanlan
§
*
†
Nano Carbon Materials, Istituto Italiano di Tecnologia (IIT), Via Livorno 60, 10144 Turin,
Italy.
‡
Department of Chemistry and Industrial Chemistry, University of Genoa, via Dodecaneso 31,
Genoa, 16145, Italy.
§
School of Chemistry and Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin,
The University of Dublin, Dublin 2, Ireland.
¶
Department of Chemistry, University of Turin, Via Giuria 7, 10125 Turin, Italy.
KEYWORDS: Thiol-ene, radical, photocatalysis, graphene, nanomaterials, metal oxide
ABSTRACT: A mild, inexpensive and general photocatalytic initiation protocol for anti-
Markovnikov hydrothiolation of olefins using carbon nanomaterial/metal oxide (Carbon NM-
MO) composites is reported. Graphene oxide (GO), nanodiamonds (ND) and carbon nano-onions
(CNO) displaying bismuth or tungsten oxide nanoparticles adhered to the surface, function as
highly efficient photocatalysts for thiol-ene ligation under both UV and visible-light-mediated
2
conditions. The straightforward catalyst preparation, excellent overall yields, ease of purification
and broad substrate scope render this a highly versatile method for bioconjugation.
Introduction
Thiyl-radical mediated reactions are widely utilized in nature for a range of essential
biochemical processes.
1
Cysteinyl residues play a key role as reactive species in many
enzymatic pathways including the deoxygenation of ribonucleotides in the de novo
synthesis of DNA precursors.
2-3
The broad application of thiyl radicals in biological
processes arises from their exceptional reactivity and chemoselectivity. It is therefore not
surprising that thiyl-radical mediated reactions have been harnessed by synthetic chemists
for a diverse range of chemical transformations.
1, 4
Thiol-ene ligation is widely utilized
for the formation of carbon-sulfur bonds in chemical synthesis
5-10
, catalysis
4
,
bioconjugation
11-12
, polymerisation
13-15
and surface modification.
16
The process is
cytocompatible
17
and adheres to the concept of a ‘click’ reaction as defined by Sharpless
in 2001.
18
Radical thiol-ene ligation reactions are typically carried out under UV
conditions in the presence of a radical initiator such as 2,2-dimethoxy-2-phenyl-
acetophenone (DPAP).
1, 7
Recently, visible-light-mediated photoredox catalysis has
emerged as a convenient alternative to UV initiation, allowing for greater substrate
compatability.
19-25
Yoon and co-workers demonstrated efficient thiol–ene reactions under
photoredox conditions using ruthenium catalysts with visible light.
23-24
Stephenson and
co-workers reported a similar strategy for radical thiol-ene coupling in which a
trichloromethyl radical genereated via single-electron reduction of
bromotrichloromethane acted as a radical chain carrier.
21
Recently, metal oxides such as
3
TiO
2
or BiO
3
have been investigated as catalysts for thiol-ene ligation, however the
requirement for stoichiometric quantities of the metal oxide or the addition of chain
carrier reagents such as BrCCl
3
render these methods unsuitable for certain biological
applications
20
(Figure 1). Despite the bourgeoning interest in photocatalysed thiol-ene
ligation, the application of carbon nanomaterials (CNMs) remains unexplored. It is known
that highly efficient photocatalysts can be prepared as composite semi-conducting
materials composed of metal oxides adhered to the surface of carbon nanomaterials.
26-29
These low-cost photocatalysts have been investigated for environmental applications
including water purification.
30-31
Carbon carbon nanomaterial/metal oxide (NM-MO)
composites are readily prepared through a number of methods including the simple
stirring of the two materials at room temperature.
32
The carbon NM-MO composite offers
a synergic effect induced by the presence of carbon materials in the hybrid
photocatalyst.
33
This is mainly attributed to the decrease of electron/hole recombination,
bandgap tuning and increase in the adsorptive active sites.
34
Herein we present the
application of both CNMs and carbon NM-MO composites as highly-efficient
photocatalysts for light-mediated thiol-ene ligation reactions. Characterisation of the
composite materials is presented and a putative mechanism for the catalytic cycle is
depicted. Substrate scope is explored across inter- and intramolecular thiol-ene ligation
and intermolecular thiol-yne reactions. Of particular note is the short reaction times,
quantitative yields and ease of purification of the products.
4
Figure 1: Pathway for photocatalysed thiol-ene ligation reactions (a) conventional UV mediated
conditions (b) visible-light mediated catalysts (c) overview of catalyst described herein.
Results and discussion
The utility of Bi
2
O
3
as a photocatalyst in visible-light-mediated thiol-ene ligation was
reported by Pfizer as part of a methodology development effort.
35
However, the metal
oxide alone was found to be an inefficient photocatalyst for thiol-ene coupling (TEC) and
BrCCl
3
was added as a chain carrier. Bi
2
O
3
, which possesses a bandgap of 2.6-2.8 eV
36
(477-442 nm), is a well-studied metal oxide semiconductor, but its efficiency as a
photocatalyst is often low because of the rapid recombination of the photo-generated
electrons and holes.
35
We set out to investigate if the photocatalytic properties of Bi
2
O
3
5
could be enhanced in a non-toxic and environmentally benign manner through the use of
carbon material/Bi
2
O
3
nano-composites. In our initial studies, the TEC between allyl
benzoate and thioacetic acid was investigated as a model system to screen suitable
photocatalysts. A range of carbon nanomaterials were screened for TEC in the presence
of a metal oxide. The results of these initial screening studies are presented in Table 1. It
was determined that all of the nanomaterials screened, when combined with Bi
2
O
3
(2
mol%) or WO
3
(2 mol%), resulted in the complete conversion of the starting allyl
benzoate
1
into the desired thioester
2
under UV irradiation after 1 hour (Table 1, entries
1-10). These promising results showed that the photocatalytic activity was general across
the range of carbon nanomaterial/metal oxide composites investigated. Absorption of
compounds
1
and
2
is negligible in the region >320 nm; therefore, under the reaction
conditions used, photocatalysis can only result from photoexcitation of the composite
nano materials. Interestingly, the nanomaterials in the absence of any metal oxide were
also able to propagate the radical reaction, albeit without full conversion to the thioester
(Table 1, entries 11-15). Overall good conversions, varying from 65% (p-CNO, entry 12)
to 94% (PEG-CNO, entry 14), were determined for all the screened nanomaterials. That
the metal oxide was required for full conversion to the desired thioester product suggests
a synergic effect induced through the combination of carbon nanomaterials and metal
oxide in the hybrid photocatalysts (see proposed mechanism).
