Efficiency and Selectivity Aspects in the C-H Functionalization of Aliphatic Oxygen Heterocycles by Photocatalytic Hydrogen Atom Transfer

Article abstract of DOI:10.1055/s-0037-1612079

The C-H to C-C conversion in aliphatic oxygen heterocycles (dioxolanes, 1,3-dioxane, or cyclic carbonates) by photocatalytic hydrogen atom transfer and subsequent trapping of the resulting radical with phenyl vinyl sulfone was investigated. The performanc

Full text of DOI:10.1055/s-0037-1612079

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
© Georg Thieme Verlag Stuttgart · New York
2019, 30, A–F
letter
A
en
C. Raviola, D. Ravelli
Letter
Synlett
Efficiency and Selectivity Aspects in the C–H Functionalization of
Aliphatic Oxygen Heterocycles by Photocatalytic Hydrogen Atom
Transfer
Carlotta Raviola
Davide Ravelli*
0
0
0
0-0
0
0
2-5
0
3
3-
4
7
6
8
0
0
0
0-0
0
0
3-2
2
0
1-
4
8
2
8
[W10O32]
4– or
Aromatic Ketones
Aliphatic
Oxygen
Heterocycles
O
O
PhotoGreen Laboratory, Department of Chemistry, University of
Pavia, viale Taramelli 12, 27100 Pavia, Italy
davide.ravelli@unipv.it
SO2Ph
SO2Ph
H
Photocatalytic
Hydrogen Atom
Transfer
Ethers,
Acetals,
Carbonates
Published as part of the Special Section 10th EuCheMS Organic
Division Young Investigator Workshop
O
Yields
up to 92%
7 examples
Received: 05.12.2018
Accepted after revision: 01.01.2019
Published online: 05.02.2019
DOI: 10.1055/s-0037-1612079; Art ID: st-2018-v0788-l
Abstract The C–H to C–C conversion in aliphatic oxygen heterocycles
(dioxolanes, 1,3-dioxane, or cyclic carbonates) by photocatalytic hydro-
gen atom transfer and subsequent trapping of the resulting radical with
phenyl vinyl sulfone was investigated. The performance of three differ-
ent photocatalysts, namely tetrabutylammonium decatungstate and
the aromatic ketones thioxanthone and 9-fluorenone, was compared.
The UV-light-absorbing decatungstate anion is more efficient and per-
mits the use of a smaller excess of hydrogen donor than the aromatic
ketones, although the ketones could be excited by visible light. Further
intramolecular selectivity studies revealed that aromatic ketones afford-
ed a higher proportion of functionalization at the acetalic versus the
ethereal positions than did the decatungstate anion.
Carlotta Raviola received her Ph.D. from the University of Pavia in
2015 (supervisor: Professor A. Albini), having spent part of her study
period at TUM (Germany) in the group of Professor T. Bach. She is
currently a postdoctoral researcher at the University of Pavia, and her
research interests focus on the photogeneration of highly reactive
intermediates (aryl cations, radicals, and diradicals) for use in in organic
synthesis.
Key words photocatalysis, hydrogen atom transfer, oxygen heterocy-
cles, chemoselectivity, radicals, C–C bond formation
Davide Ravelli is currently a researcher at the PhotoGreen Laboratory
of the University of Pavia. His main research interests are in the area of
photochemical reactions and their attending applications in various
fields, particularly in organic synthesis. He is very interested in the dis-
covery of methods for the facile generation of valuable intermediates
(mainly radicals). In recent years, he has been deeply involved in the
study of decatungstate-mediated photocatalyzed reactions (particular-
ly, those involving a hydrogen atom transfer step).
Oxygen heterocycles are an important family of hetero-
cyclic systems.1 These privileged structures are present in
many naturally occurring compounds, notably carbohy-
drates and nucleosides among biomolecules, as well as in a
plethora of compounds having pharmaceutical activities.
According to a recent report, oxygenated derivatives are the
second-most-common type of heterocycles present as a
structural motif in pharmaceuticals approved by the US
Food and Drug Administration. Interestingly, the majority
(around 90%) of the encountered oxygen heterocycles are
nonaromatic in character, with pyranoses, furanoses, mac-
rolactones, morpholines, and dioxolanes occupying the first
five positions in the ranking in terms of their relative abun-
dance.2 Accordingly, the construction and functionalization
of these scaffolds is an important topic for synthetic chem-
ists. A classic example is the Paal–Knorr synthesis of furans,
whereas more-recent strategies make extensive use of tran-
sition-metal catalysis.3 Interestingly, microwave-assisted
protocols have also been developed.4
An intriguing alternative is represented by photocata-
lytic strategies,5–7 in which a photoactive catalyst is respon-
sible for light absorption and, once in its excited state, for
the activation of the actual substrate of the process.8 This
step leads to the formation of highly reactive intermediates,
mostly open-shell radical ions or radicals, which, in turn,
are responsible for the observed chemistry. In the particular
case of aliphatic oxygen heterocycles, the photocatalytic
approach opens the way to the direct functionalization of
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–F

B
C. Raviola, D. Ravelli
Letter
Synlett
C–H bonds through a hydrogen atom transfer (HAT) step.9
Thus, a few photocatalysts10 or photogenerated HAT re-
agents11 are capable of directly cleaving C–H bonds in the
starting material. Along this line, our group recently ex-
plored the use of the decatungstate anion, as its tetrabu-
tylammonium salt [(Bu4N)4(W10O32); TBADT] as a photocat-
alyst, thanks to the peculiar reactivity of its excited state,
which has a partial alkoxy-radical character.12,13 Thus,
TBADT smoothly promoted C–H to C–C conversions in vari-
ous hydrogen donors, including tetrahydrofuran (THF), 1,4-
dioxane, oxetanes, 1,3-benzodioxoles, and a few lactones,
through trapping of the photogenerated radicals with elec-
tron-deficient olefins (α,β-unsaturated esters, ketones, ni-
triles, sulfones, etc.) in a conjugate radical addition process
[see Scheme 1(a)]. Upon back-HAT, the resulting radical ad-
duct finally led to the functionalized heterocycle, while the
photocatalyst was restored to its original state.12,13 The re-
actions were routinely carried out under UV irradiation
(λEXC = 310 or 366 nm), but solar radiation was also demon-
strated to be a convenient choice.12
In this work, we offer a direct comparison of the differ-
ent reactivities shown by the decatungstate anion and by a
selection of (visible-light absorbing) aromatic ketones in
the functionalization through photocatalytic HAT of select-
ed families of aliphatic oxygen heterocycles. Furthermore,
we also investigated how the choice of the photocatalyst
modifies the intramolecular chemoselectivity of the C–H
cleavage step [Scheme 1(b)]. At the beginning, we per-
formed an optimization of the reaction conditions by
studying the addition of THF (1a) to phenyl vinyl sulfone
(2), taken as a model trap and then used throughout the
rest of the work, to give the adduct 3a in the presence of se-
lected photocatalysts [Scheme 1(b)].21 We had already in-
vestigated this reaction in the presence of TBADT (2 mol%),
and we obtained 3a in 59% yield upon irradiation of a MeCN
solution containing 1a (5 equiv) and 2 (0.1 M) for 24 hours
with phosphor-coated lamps (12 × 15 W) that emitted radi-
ation centered at 366 nm.22 Interestingly, the yield of 3a in-
creased to 90% (as determined by GC analysis) when the ir-
radiation was performed for 20 hours in a solar simulator
equipped with a 1500 W xenon lamp (500 W·m–2 light in-
tensity; see Table 1, entry 1). When the reaction was per-
formed on a 0.5 mmol scale, 3a was isolated in 86% yield
after silica-gel chromatography. Next, we tested the aro-
matic ketones thioxanthone and 9-fluorenone as POCs7 un-
der analogous reaction conditions. Thus, irradiation of a
solution of 1a and 2 in the presence of thioxanthone (20
mol%) in dichloromethane (for reasons of solubility) under
solar-simulated conditions led to a reasonable consumption
of 2 (64%), with the formation of 3a in 88% yield based on
the consumed 2 (56% overall yield; entry 2). In the presence
of 9-fluorenone (20 mol%), the reaction gave poor results,
and 3a was obtained in only 33% yield at 24% consumption
of 2 (entry 3). Because they can absorb in the visible-light
range [see Supporting Information (SI); Figure S1], aromatic
ketones can also operate as POCs upon irradiation at λ > 400
nm. We therefore tested their reactivities upon irradiation
with a 1 W violet LED (λ = 405 ± 5 nm; 130 W·m–2 light in-
tensity). With both POCs, product 3a was formed in a low
yield and, again, with incomplete consumption of 2 (entries
4 and 5). In the attempt to improve both the yield and the
conversion of the starting olefin, we decided to adopt a
greater excess of the hydrogen donor (3 M; 30 equiv). Inter-
estingly, in the case of thioxanthone, the desired adduct 3a
was obtained in 87% isolated yield (entry 6), a similar value
to what obtained with TBADT (entry 1). On the other hand,
with 9-fluorenone, we failed to achieve complete consump-
tion of 2, even after irradiation for 30 hours (entries 7 and
8). Importantly, in all cases, the reaction required both light
and the presence of the chosen photocatalyst to proceed, as
demonstrated by blank experiments (See SI; Table S1). With
these preliminary results in hand, we extended the reaction
to 2,2-dimethyl-1,3-dioxolane (1b). The reaction proceeded
satisfactorily in the presence of TBADT, giving 3b in 55% iso-
lated yield with a complete consumption of 2 (entry 9). On
the other hand, aromatic ketones gave unsatisfactory re-
sults, even when 1b was used in a large excess (50 equiv),
and the yields were around 10% (entries 10 and 11). Finally,
a) Previous work:
R
H
PC*
PC = TBADT - (nBu4N)4[W10O32
]
hν = UV-B or solar light
hν
O
O
H
R
=
H
R
( )n
PC
EWG
H-PC
H
O
n = 1, 2
O
O
O
EWG
PC = Photocatalyst
b) This work:
EWG
R
H
H
R
( )n
O
H
O
S
4–
PC = TBADT, thioxanthone, 9-fluorenone
hν = Solar or VIS light
O
H
Thioxanthone
=
H
R
O
O
O
O
R
O
R'
O
R
H
4 (nBu4N)+
R, R' = H or Me
O
H
TBADT
R = H or Me
9-Fluorenone
Scheme 1 C–H functionalization of aliphatic oxygen heterocycles through
photocatalytic hydrogen atom transfer
Other groups have exploited the similar HAT reactivity
displayed by the excited states of aromatic ketones (e.g.,
benzophenone, 4-benzoylpyridine, quinones, etc.)10b,14,15
and by the dye eosin Y16 in a wide range of synthetically ap-
pealing processes, including C–C,17 C–N,18 and C–halogen19
bond-forming reactions, as well as in oxidations,20 among
others. Indeed, a few of these photoorganocatalysts (POCs)7
have also been demonstrated to operate under visible-light
irradiation.16,17d–f,18–20
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–F

C
C. Raviola, D. Ravelli
Letter
Synlett
we tested the reactivity of a cyclic carbonate, namely eth-
ylene carbonate (1c), as a hydrogen donor. In this case, the
efficiency of the process dropped significantly, and 3c was
obtained in only 57% isolated yield in the presence of
TBADT and 50 equiv of 1c (entries 12–14), whereas both
the investigated POCs failed to give the desired adduct 3c
(entries 15 and 16).
Entry 1 (M)
16 1c (5)
Conditionsb
Consumptionc Yieldc
(%) of 2
(%) of 3
thioxanthone (20 mol%)
CH2Cl2, LED
40
n.d.
a Irradiations were carried out in Pyrex vials on a 0.1 mmol scale with MeCN
(for TBADT or 9-fluorenone) or CH2Cl2 (for thioxanthone) as the solvent.
Solutions were bubbled with N2 for 5 min before irradiation.
b SolarBox: irradiation was performed with a solar-light simulator equipped
with a 1.5 kW Xe lamp (500 W·m–2 light intensity). LED: irradiation was per-
formed with a 405 ± 5 nm LED (1 W; 130 W·m–2 light intensity).
c Except where otherwise noted, the consumption of 2 and the yield of 3
were determined by GC with dodecane (1 μL·mL–1) as internal standard.
Yields of 3 are expressed on the basis of the consumed 2 and can interpret-
ed as ‘selectivity’ values.
Table 1 Optimization of the Reaction Conditions, and Initial Experi-
mentsa
Entry 1 (M)
Conditionsb
Consumptionc Yieldc
d Isolated yield from a reaction performed on a 0.5 mmol scale after chro-
matography (silica gel, cyclohexane–EtOAc).
(%) of 2
(%) of 3
e Irradiation for 30 h.
O
CONDITIONS
hν, 20 h, N2
f n.d. = not detected.
SO2Ph
+
O
SO2Ph
1a
2 (0.1 M)
3a
1
2
3
4
5
6
7
8
1a (0.5)
TBADT (2 mol%), MeCN
SolarBox
100
64
90
To examine the possibility of performing selective C–H
to C–C conversions, we then moved on to study a series of
hydrogen donors containing various positions prone to
functionalization, and the results are summarized in Table
2. We initially tested the reactivity of 1,3-dioxolane (1d) in
the presence of the same photocatalysts as used above
under conditions similar to those adopted for 1a and 1b.
Thus, the use of TBADT gave a 42% overall yield of a 58:42
mixture of products 3d and 4d, resulting from the function-
alization at the acetalic and ethereal positions, respectively
(Table 2, entry 1).
(86)d
88
1a (0.5)
1a (0.5)
1a (0.5)
1a (0.5)
1a (3)
thioxanthone (20 mol%)
CH2Cl2, SolarBox
9-fluorenone (20 mol%)
MeCN, SolarBox
24
33
40
24
thioxanthone (20 mol%)
CH2Cl2, LED
78
9-fluorenone (20 mol%)
MeCN, LED
37
thioxanthone (20 mol%)
CH2Cl2, LED
100
78
92
(87)d
1a (3)
9-fluorenone (20 mol%)
MeCN, LED
71
Table 2 Intramolecular selectivities in the C–H to C–C functionaliza-
1a (3)
9-fluorenone (20 mol%)
MeCN, LEDe
85
74
tion of aliphatic oxygen heterocycles.a
O
Entry 1 (M)
Conditionsb
Consumptionc Yieldc
O
CONDITIONS
SO2Ph
(%) of 2
(%) of 3
+
O
SO2Ph
O
hν, 20 h, N2
O
O
O
1b
2 (0.1 M)
3b
O
CONDITIONS
hν, 20 h, N2
O
SO2Ph
+
+
9
10
11
1b (0.5)
1b (5)
TBADT (2 mol%)
MeCN, SolarBox
100
66
55d
6
O
1d
2 (0.1 M)
SO2Ph
SO2Ph
3d
4d
9-fluorenone (20 mol%)
MeCN, LED
1
2
3
1d (0.5) TBADT (2 mol%)
100
42d
MeCN, SolarBox
(3d/4d = 58:42)e
1b (5)
thioxanthone (20 mol%)
CH2Cl2, LED
82
12
1d (5)
1d (5)
thioxanthone (20 mol%) 100
CH2Cl2, LEDf
59d
(3d/4d = 90:10)e
O
O
O
CONDITIONS
SO2Ph
9-fluorenone (20 mol%)
MeCN, LEDf
55
33
O
+
(3d/4d = 92:8)e
O
SO2Ph
O
hν, 20 h, N2
1c
2 (0.1 M)
3c
O
O
O
12
13
14
15
1c (0.5)
1c (0.5)
1c (5)
TBADT (2 mol%)
MeCN, SolarBox
82
90
16
O
CONDITIONS
O
+
+
SO2Ph
O
hν, 20 h, N2
SO2Ph
TBADT (4 mol%)
MeCN, SolarBox
16
SO2Ph
1e
2 (0.1 M)
3e
4e
TBADT (2 mol%)
MeCN, SolarBox
100
21
57d
n.d.f
4
1e (0.5) TBADT (2 mol%)
100
3e, 41d
4e, 27d
(3e/4e = 60:40)
MeCN, SolarBox
1c (5)
9-fluorenone (20 mol%)
MeCN, LED
5
1e (5)
1e (5)
thioxanthone (20 mol%)
71
30
15
CH2Cl2, LEDe
6
9-fluorenone (20 mol%)
MeCN, LEDe
traces
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–F

D
C. Raviola, D. Ravelli
Letter
Synlett
Table 2 (continued)
changing to 2-methyl-1,3-dioxolane (1f), which has a ter-
tiary acetalic position, the reaction in the presence of
TBADT gave full consumption of 2 in the presence of only a
threefold excess of 1f. Indeed, the functionalization at the
acetalic position occurred exclusively, although the desired
product 3f was accompanied by traces of compound 3f′ re-
sulting from deprotection of the acetal group. Notably, the
formation of this undesired byproduct could be suppressed
by performing the reaction in the presence of a mild base
(NaHCO3, 1 equiv),23 giving product 3f as the only isolated
adduct in 74% yield (entries 7 and 8). Thioxanthone or 9-
fluorenone again required the use of a large excess of hy-
drogen donor (50 equiv). In the first case, 3f was formed in
35% yield along with 18% of 3f′, whereas in the latter case,
only traces of the adduct 3f were found by GC analysis (en-
tries 9 and 10). In both cases, the addition of Cs2CO3 (1
equiv) pushed the reaction towards the formation of the
desired adduct 3f (entries 11 and 12) while limiting the for-
mation of 3f′. Finally, functionalization of propylene car-
bonate 1g, in which 50 equivalents of 1g were used regard-
less of the chosen photocatalyst, led to selective formation
of 3g in 49% isolated yield in the presence of TBADT (entry
13), whereas the aromatic ketones failed to give any trace of
products (entries 14 and 15).
Entry 1 (M)
Conditionsb
Consumptionc Yieldc
(%) of 2
(%) of 3
O
O
O
SO2Ph
O
O
CONDITIONS
+
SO2Ph
+
3f
O
hν, 20 h, N2
4f
SO2Ph
SO2Ph
1f
2 (0.1 M)
3f'
O
7
1f (0.3) TBADT (2 mol%)
100
100
3f, 62
(3f′; traces)
MeCN, SolarBox
8
1f (0.3) TBADT (2 mol%)
NaHCO3 (1 equiv)
3f, 74d
MeCN, SolarBox
9
10
11
1f (5)
1f (5)
1f (5)
thioxanthone (20 mol%) 100
CH2Cl2, LED
3f, 35d
(3f′; 18%)d
9-fluorenone (20 mol%)
MeCN, LED
37
3f, traces
thioxanthone (20 mol%) 100
Cs2CO3 (1 equiv)
3f, 71
(3f′; 4%)
CH2Cl2, LED
12
1f (5)
9-fluorenone (20 mol%) 100
Cs2CO3 (1 equiv)
3f, 56
MeCN, LED
O
O
O
O
O
+
O
O
CONDITIONS
O
SO2Ph
+
The results reported above show some interesting
trends. TBADT consistently demonstrated superior reactivi-
ty to that of the POCs used, because the desired adducts
were obtained in the presence of a lower catalyst loading (2
mol% versus 20 mol%) and a lower excess of the hydrogen
donor (often 5-fold as against 50-fold). However, TBADT ab-
sorbs UV radiation exclusively, and it required the use of a
solar-simulated light source, whereas the two POCs operat-
ed under irradiation by a violet light. Furthermore, thioxan-
thone was shown to be a superior photocatalyst to 9-fluo-
renone, as demonstrated by the higher conversions of the
starting materials and the higher yields. All the photocata-
lysts showed a lower reactivity in the functionalization of
1b compared with that of 1a (with lower yields and/or a
higher excess of hydrogen donor required). This might be
due to steric effects connected with the presence of the two
methyl groups at the acetalic position. Alternatively, it
might be due to polar effects that disfavor the formation of
the α-oxyalkyl radical intermediate in 1b with respect to 1a
due to the presence of the electron-withdrawing β′-oxygen
atom exerting a certain deactivating effect on HAT.24 Simi-
larly, electronic effects played a role in the functionalization
of cyclic carbonates (e.g., 1c), which required more-severe
conditions (a greater excess of hydrogen donor) than in the
case of 1a and 1b, and reacted only in the presence of
TBADT, the tested ketones being ineffective in this process.
The low reactivity observed in the case of the ketones
might be related to the ππ* character of their lowest-lying
triplet excited states, responsible for the key HAT step (as
opposed to the nπ* character of more-reactive ketones,
such as benzophenone).25
O
hν, 20 h, N2
1g
2 (0.1 M)
SO2Ph
SO2Ph
3g
4g
13
1g (5)
1g (5)
1g (5)
TBADT (2 mol%)
MeCN, SolarBox
100
58
3g, 49d
14
15
thioxanthone (20 mol%)
CH2Cl2, LED
n.d.g
n.d.
9-fluorenone (20 mol%)
MeCN, LED
28
a–d See Table 1.
e The ratio of 3 to 4 was determined by 1H NMR (see SI).
f Irradiation for 30 h.
g n.d. = not detected.
Whereas the hydrogen donor was used in a fivefold ex-
cess in the case of TBADT, thioxanthone required the use of
50 equivalents of 1d, affording a 90:10 mixture of 3d and
4d in 59% overall yield upon irradiation for 30 h (Table 2,
entry 2). A similar product ratio was consistently obtained
when 9-fluorenone was used as the POC, although the de-
sired adduct was formed in low yield and with a partial
consumption of 2 (entry 3). Next, we moved to six-mem-
bered oxygen heterocycles, and we used 1,3-dioxane (1e) as
the hydrogen donor. The reaction in the presence of TBADT
afforded two different products, 3e (41% isolated yield) and
4e (27% isolated yield), resulting from the functionalization
at the acetalic and ethereal positions, respectively (3e/4e =
60:40; entry 4). On the other hand, thioxanthone promoted
the exclusive formation of 3e, albeit with a poor perfor-
mance according to GC analysis, whereas 9-fluorenone only
gave traces of the desired adduct 3e (entries 5 and 6). On
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–F

E
C. Raviola, D. Ravelli
Letter
Synlett
Turning to the intramolecular selectivity aspect, we ini-
tially evaluated the competition between functionalization
at the acetalic and the ethereal methylenic positions in 1d
and 1e, where an α,α-dioxyalkyl or an α-oxyalkyl radical is
involved, respectively. With these substrates, products 3
were consistently formed in higher amounts than products
4. The choice of the photocatalyst, however, had an effect,
as TBADT gave 3 and 4 in a ratio of about 3 (statistically cor-
rected), whereas for the ketones this value was >18 (statisti-
cally corrected). Indeed, a clean reaction occurred in the
case of 1e in the presence of thioxanthone, where 3e was
the only product formed. In the particular case of the func-
tionalization of 1,3-dioxolane (1d) promoted by (aromatic)
ketones, similar trends have been reported in the literature.
Whereas some reports indicated a completely selective
functionalization at the acetalic position,16,17a–c in a couple
of cases, a distribution of products similar to that found
here was described, notably in the acetone-initiated alkyla-
tion of 1,3-dioxolane by terminal olefins.26 Interestingly, the
same selectivity pattern found here for aromatic ketones
has also been observed in the functionalization of 1d
through HAT promoted by a photogenerated chlorine
atom.11c On the other hand, the intramolecular competition
between the functionalization at the acetalic versus the
ethereal positions in the presence of TBADT has received
limited attention.27 The different selectivity observed for
the decatungstate anion compared with the tested POCs
might be related to the different lifetimes of the relevant re-
active states, where a short-lived species reacts with poor
discrimination between the available sites. Indeed, whereas
in the case of the decatungstate anion, the state responsible
for the observed chemistry (named wO) has a lifetime of
about 50–60 ns in acetonitrile,28 the triplet states of the
ketones employed here show much longer lifetimes, of the
order of microseconds,25a,c in turn leading to predominant
or exclusive functionalization at the acetalic position.
The presence of a methyl group, however, dramatically
changed the reaction outcome, as observed in the case of 1f.
Thus, regardless of the choice of photocatalyst, the (tertia-
ry) acetalic position was functionalized exclusively to give
3f in all cases. An undesired byproduct 3f' was observed,
presumably formed through spontaneous deprotection of
the dioxolane moiety of product 3f. Its formation could,
however, be suppressed by the addition of an (insoluble) in-
organic base. Also, this agrees well with previous reports in
which UV-light-induced, benzophenone-photosensitized,
hydrogen abstraction from 2-alkyl-1,3-dioxolanes has been
described as taking place at the 2-position exclusively.29
Finally, a similar selectivity towards the tertiary position
was also observed in the case of propylene carbonate (1g),
albeit only in the presence of TBADT. This is fully consistent
with our previous investigation on lactones, where the
presence of a tertiary position α to the oxygen atom drove
the process toward exclusive functionalization of that posi-
tion.30
In conclusion, the present work describes the different
capabilities of selected HAT photocatalysts in promoting
the functionalization of aliphatic oxygen heterocycles. We
found that TBADT was the more reactive photocatalyst, re-
quiring a lower loading and permitting the use of substrates
in lower excesses than usually required for the aromatic ke-
tones 9-fluorenone and thioxanthone. However, these ke-
tones offer the possibility of performing more-selective re-
actions, as demonstrated in the reported examples of intra-
molecular selectivity.
Funding Information
We thank the MIUR for financial support (SIR Project ‘Organic Synthe-
sis via Visible Light Photocatalytic Hydrogen Transfer’; Code:
RBSI145Y9R).()
Acknowledgment
We thank Dr. Silvia Garbarino (University of Pavia) for preliminary
experiments and Professor Stefano Protti (University of Pavia) for
fruitful discussion.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1612079.
S
u
p
p
orti
n
gInformati
o
n
S
u
p
p
orti
n
gInformati
o
n
References and Notes
(1) Handbook of Heterocyclic Chemistry; Katritzky, A. R.; Ramsden,
C. A.; Joule, J. A.; Zhdankin, V. V., Ed.; Elsevier: Oxford, 2010, 3rd
ed..
(2) Delost, M. D.; Smith, D. T.; Anderson, B. J.; Njardarson, J. T. J. Med.
Chem. 2018, 61, 10996.
(3) (a) Deiters, A.; Martin, S. F. Chem. Rev. 2004, 104, 2199.
(b) Chemler, S. R.; Copeland, D. A. Top. Heterocycl. Chem. 2013,
32, 39. (c) Egi, M.; Akai, S. Heterocycles 2015, 91, 931. (d) Novák,
Z.; Kotschy, A. Top. Heterocycl. Chem. 2014, 45, 231.
(4) Kaur, N. Synth. Commun. 2014, 44, 3483.
(5) Visible Light Photocatalysis in Organic Chemistry; Stephenson, C.
R. J.; Yoon, T. P.; MacMillan, D. W. C., Ed.; Wiley-VCH: Wein-
heim, Germany, 2018.
(6) Ravelli, D.; Protti, S.; Fagnoni, M. Chem. Rev. 2016, 116, 9850.
(7) (a) Romero, N. A.; Nicewicz, D. A. Chem. Rev. 2016, 116, 10075.
(b) Sideri, I. K.; Voutyritsa, E.; Kokotos, C. G. Org. Biomol. Chem.
2018, 16, 4596.
(8) Crespi, S.; Fagnoni, M. Top. Heterocycl. Chem. 2018, 54, 1.
(9) Special issue: Hydrogen Atom Transfer, Acc. Chem. Res., 2018, 51,
2601.
(10) (a) Capaldo, L.; Ravelli, D. Eur. J. Org. Chem. 2017, 2017, 2056.
(b) Protti, S.; Fagnoni, M.; Ravelli, D. ChemCatChem 2015, 7,
1516.
(11) For recent selected examples, see: (a) Deng, H.-P.; Zhou, Q.; Wu,
J. Angew. Chem. Int. Ed. 2018, 57, 12661. (b) Le, C.; Liang, Y.;
Evans, R. W.; Li, X.; MacMillan, D. W. C. Nature 2017, 547, 79.
(c) Nielsen, M. K.; Shields, B. J.; Liu, J.; Williams, M. J.; Zacuto, M.
J.; Doyle, A. G. Angew. Chem. Int. Ed. 2017, 56, 7191. (d) Shaw, M.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–F

F
C. Raviola, D. Ravelli
Letter
Synlett
H.; Shurtleff, V. W.; Terrett, J. A.; Cuthbertson, J. D.; MacMillan,
D. W. C. Science 2016, 352, 1304. (e) Choi, G. J.; Zhu, Q.; Miller, D.
C.; Gu, C. J.; Knowles, R. R. Nature 2016, 539, 268.
4-[2-(Phenylsulfonyl)ethyl]-1,3-dioxolan-2-one (3c)
Colorless oil; yield: 73 mg (57%). IR (neat): 2942, 1768, 1131
cm−1 1H NMR (CDCl3, 300 MHz): δ = 7.95–7.90 (m, 2 H), 7.75–
.
(12) Ravelli, D.; Protti, S.; Fagnoni, M. Acc. Chem. Res. 2016, 49, 2232.
(13) Ravelli, D.; Fagnoni, M.; Fukuyama, T.; Nishikawa, T.; Ryu, I. ACS
Catal. 2018, 8, 701.
7.70 (m, 1 H), 7.65–7.60 (m, 2 H), 4.95–4.90 (m, 1 H), 4.65–4.50
(m, 1 H), 4.15–4.10 (m, 1 H), 3.35–3.20 (m, 2 H), 2.40–2.10 (m, 2
H). 13C NMR (CDCl3, 75 MHz): δ = 154.4, 138.4, 134.2 (CH), 129.5
(CH), 127.9 (CH), 74.5 (CH), 68.8 (CH2), 51.6 (CH2), 27.3 (CH2).
Anal. Calcd for C11H12O5S: C, 51.55; H, 4.72. Found: C, 51.6; H,
4.7.
(14) Kamijo, S. Top. Heterocycl. Chem. 2018, 54, 71.
(15) Hoffmann, N. J. Phys. Org. Chem. 2015, 28, 121.
(16) Fan, X.-Z.; Rong, J.-W.; Wu, H.-L.; Zhou, Q.; Deng, H.-P.; Tan, J. D.;
Xue, C.-W.; Wu, L.-Z.; Tao, H.-R.; Wu, J. Angew. Chem. Int. Ed.
2018, 57, 8514.
4-Methyl-4-[2-(phenylsulfonyl)ethyl]-1,3-dioxolan-2-one
(3g)
(17) (a) Manfrotto, C.; Mella, M.; Freccero, M.; Fagnoni, M.; Albini, A.
J. Org. Chem. 1999, 64, 5024. (b) Geraghty, N. W. A.; Lally, A.
Chem. Commun. 2006, 4300. (c) Dondi, D.; Protti, S.; Albini, A.;
Mañas Carpio, S.; Fagnoni, M. Green Chem. 2009, 11, 1653.
(d) Kamijo, S.; Kamijo, K.; Maruoka, K.; Murafuji, T. Org. Lett.
2016, 18, 6516. (e) Kawaai, K.; Yamaguchi, T.; Yamaguchi, E.;
Endo, S.; Tada, N.; Ikari, A.; Itoh, A. J. Org. Chem. 2018, 83, 1988.
(f) Papadopoulos, G. N.; Voutyritsa, E.; Kaplaneris, N.; Kokotos,
C. G. Chem. Eur. J. 2018, 24, 1726.
(18) (a) Papadopoulos, G. N.; Limnios, D.; Kokotos, C. G. Chem. Eur. J.
2014, 20, 13811. (b) Papadopoulos, G. N.; Kokotos, C. G. J. Org.
Chem. 2016, 81, 7023. (c) Papadopoulos, G. N.; Kokotos, C. G.
Chem. Eur. J. 2016, 22, 6964.
(19) (a) Xia, J.-B.; Zhu, C.; Chen, C. J. Am. Chem. Soc. 2013, 135, 17494.
(b) Xia, J.-B.; Zhu, C.; Chen, C. Chem. Commun. 2014, 50, 11701.
(c) Bume, D. D.; Pitts, C. R.; Jokhai, R. T.; Lectka, T. Tetrahedron
2016, 72, 6031.
(20) Tachikawa, Y.; Cui, L.; Matsusaki, Y.; Tada, N.; Miura, T.; Itoh, A.
Tetrahedron Lett. 2013, 54, 6218.
White solid; yield: 66 mg (49%); mp 117–118 °C. IR (KBr): 2923,
1801, 1281, 1064 cm−1 1H NMR (CDCl3, 300 MHz): δ = 7.95–
.
7.90 (m, 2 H), 7.75–7.70 (m, 1 H), 7.65–7.60 (m, 2 H), 4.25–4.15
(m, 2 H), 3.25–3.20 (m, 2 H), 2.25–2.20 (m, 2 H), 1.15 (s, 3 H). 13
C
NMR (CDCl3, 75 MHz): δ = 153.5, 138.4, 134.2 (CH), 129.5 (CH),
127.9 (CH), 81.5, 74.0 (CH), 50.7 (CH2), 31.6 (CH2), 24.2 (CH3).
Anal. Calcd for C12H14O5S: C, 53.32; H, 5.22. Found: C, 53.3; H,
5.2.
(22) Ravelli, D.; Montanaro, S.; Zema, M.; Fagnoni, M.; Albini, A. Adv.
Synth. Catal. 2011, 353, 3295.
(23) The decatungstate anion is known to be unstable under strongly
basic conditions, although it tolerates the presence of NaHCO3
as an insoluble base; see: Ravelli, D.; Albini, A.; Fagnoni, M.
Chem. Eur. J. 2011, 17, 572.
(24) Similar behavior has recently been observed in the case of HAT
from alkanols and alkanediols; see: Salamone, M.; Ortega, V. B.;
Martin, T.; Bietti, M. J. Org. Chem. 2018, 83, 5539.
(25) (a) Iyer, A.; Clay, A.; Jockusch, S.; Sivaguru, J. J. Phys. Org. Chem.
2017, 30, e3738. (b) Soep, B.; Mestdagh, J.-M.; Briant, M.;
Gaveau, M.-A.; Poisson, L. Phys. Chem. Chem. Phys. 2016, 18,
22914. (c) Santhamurthy, A. R.; Rao, T. A. P.; Sobhanadri, J.;
Murthy, V. R. K. J. Phys. Soc. Jpn. 1998, 67, 1220.
(26) (a) Rosenthal, I.; Elad, D. J. Org. Chem. 1968, 33, 805. (b) Graalfs,
H.; Fröhlich, R.; Wolff, C.; Mattay, J. Eur. J. Org. Chem. 1999,
1057.
(27) Dondi, D.; Fagnoni, M.; Albini, A. Chem. Eur. J. 2006, 12, 4153.
(28) De Waele, V.; Poizat, O.; Fagnoni, M.; Bagno, A.; Ravelli, D. ACS
Catal. 2016, 6, 7174.
(29) Mosca, R.; Fagnoni, M.; Mella, M.; Albini, A. Tetrahedron 2001,
57, 10319.
(30) Yamada, K.; Fukuyama, T.; Fujii, S.; Ravelli, D.; Fagnoni, M.; Ryu,
I. Chem. Eur. J. 2017, 23, 8615.
(21) C–H Functionalization of Aliphatic Oxygen Heterocycles;
General Procedure
A solution of phenyl vinyl sulfone (2; 0.1 M), the chosen ali-
phatic oxygen heterocycle 1 (0.3–5 M), the photocatalyst
(TBADT: 2 mol%; 9-fluorenone or thioxanthone: 20 mol%), and
the base (NaHCO3 or Cs2CO3; 1 equiv, if required) in the chosen
medium (MeCN or CH2Cl2) was purged with N2 for 5 min then
irradiated. The reaction course and the product distribution
were monitored by GC analysis. The photolyzed solution was
concentrated in vacuo, and the resulting residue was purified by
column chromatography (silica gel, cyclohexane–EtOAc) to give
product(s) 3 and/or 4.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–F