Decatungstate Photocatalyzed Acylations and Alkylations in Flow via Hydrogen Atom Transfer

Article abstract of DOI:10.1002/adsc.201500483

A set of atom-economical radical conjugate addition reactions of alkyl and acyl radicals onto electron-poor olefins or diisopropyl azodicarboxylate has been carried out on a multi-gram scale under continuous flow conditions. The process is based on the us

Full text of DOI:10.1002/adsc.201500483

UPDATES
DOI: 10.1002/adsc.201500483
Decatungstate Photocatalyzed Acylations and Alkylations in
Flow via Hydrogen Atom Transfer
Filippo Bonassi,a Davide Ravelli,a,* Stefano Protti,a,* and Maurizio Fagnonia
a
Photogreen Lab, Department of Chemistry, University of Pavia, viale Taramelli 12, 27100 Pavia, Italy
Fax: (+39)-0382-987-323; phone: (+39)-0382-987-198; e-mail: davide.ravelli@unipv.it or prottistefano@gmail.com
Received: May 19, 2015; Revised: August 6, 2015; Published online: November 6, 2015
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500483.
Abstract: A set of atom-economical radical conju-
gate addition reactions of alkyl and acyl radicals
onto electron-poor olefins or diisopropyl azodicar-
boxylate has been carried out on a multi-gram scale
under continuous flow conditions. The process is
based on the use of the inorganic photocatalyst tet-
rabutylammonium decatungstate (TBADT), which
actions have also been applied to photochemical pro-
cesses, thus overcoming the typical drawbacks of
batch conditions that often make this technique un-
derutilized in general organic synthesis.[2] Indeed,
a more uniform absorption of light is obtained by re-
ducing the size of the reaction channels. A residence-
time shortening results and allows for an improve-
ment of the efficiency and the selectivity of the pro-
cess, even at high substrate concentrations, while
À
is capable to activate selectively a variety of C H
bonds in different substrates, including aldehydes,
amides, ethers and alkanes. A wide range of syn-
thetic targets has been synthesized according to this
procedure, including 1,4-difunctionalized derivatives
(e.g., 1,4-diketones or keto esters). All the reactions
have been carried out in a meso-scale flow photo-
reactor consisting in coils of UV-transparent FEP
tubing (fluorinated ethylene propylene) wrapped
around a water-cooled 500W medium pressure mer-
cury vapor lamp. The use of such a photochemical
apparatus caused a reduction of the residence time,
a notable increase of the STY (space time yield)
and of the productivity values with respect to those
measured for the corresponding batch processes,
often leading to an improvement of the overall sus-
tainability of the process (process mass intensity –
PMI – values down to 10 kgkgÀ1).
avoiding the generation of secondary products.[3]
A
uniform irradiation throughout the reaction mixture
was recently achieved having recourse to microflow
(e.g., lab-on-a-chip apparatus)[4] or macroflow[2,5,6] sys-
tems. Meso-scale home-made reactors (tubing with
optical path >1 mm)[7] are mainly assembled by
simply wrapping a tube (made of a polyfluorinated
UV-transparent polymer) around the light source.[8]
Nevertheless, a recent work of Booker-Milburnꢀs
group raises the issue on the usefulness of photo-
chemical processes in flow, since in most cases the ob-
served yield and productivity values are rather similar
to those obtained under batch conditions.[9] Most of
the reactions investigated were, however, photocy-
cloadditions and rearrangements and the authors con-
cluded that the results may be different when consid-
ering other photochemical reactions (e.g., photocata-
lyzed processes, photooxygenations, etc.).[5]
Keywords: decatungstate salts; flow reactions; hy-
drogen atom transfer; photocatalysis; waste minimi-
zation
We have been studying since some years ago photo-
catalyzed hydrogen atom transfer (HAT) reactions
À
À
for the green formation of valuable C C and C N
bonds.[10] In particular, we found that TBADT (tetra-
butylammonium decatungstate) is a robust and versa-
tile catalyst capable, when excited, to generate
À
Introduction
carbon-centered radicals by cleavage of a C H bond
in organic molecules.[10,11] We further demonstrated
The use of continuous-flow processes is widely recog- that the TBADT-photocatalyzed addition of alde-
nized by the chemical community as a valid tool to hydes onto electron-poor olefins can be carried out
perform organic reactions for the smooth, large-scale by using
a flow photoreactor (reactor volume:
preparation of valuable compounds (including natural 12 mL), where the reaction mixture was circulated in
products), also thanks to the process intensification a polytetrafluoroethylene tubing (PTFE, outer diame-
achieved in multi-reactor systems.[1] Recently, flow re- ter: 1.6 mm; inner diameter: 1.3 mm) wrapped around
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Filippo Bonassi et al.
ter: 3.18 mm; inner diameter: 2.1 mm; reactor
volume: 50 mL) wrapped around a traditional water-
cooled 500W medium pressure Hg vapor lamp (Fig-
ure S1, Supporting information).
Results
Several TBADT-photocatalyzed reactions previously
carried out under batch conditions in our laborato-
ry[14–20] were then investigated by using the upgraded
flow photoreactor, as summarized in Scheme 2. Ali-
phatic and aromatic aldehydes,[14] amides (DMF, N-
methylformamide),[15] ethers and acetals (oxetane,
THF, 1,4-dioxane, 1,3-benzodioxole),[16] aliphatic ni-
triles,[17] alkylbenzenes,[18] and alkanes (cyclohex-
ane)[19] have been chosen as carbon-centered radical
precursors (R-H, 1a–m). In turn, electron-poor olefins
2a–f, h–j and azodicarboxylate 2g[20] have been adopt-
ed as radical traps (Scheme 2). The photocatalyst was
used in a 0.4–2 mol% amount, while the flow rate
adopted was in the 0.2–0.5 mLminÀ1 range and
MeCN was used as the solvent throughout this study,
with the only exception of the reactions involving al-
kylbenzenes, where
a 0.5M LiClO4 solution in
a MeCN/water 5:1 mixture was employed.[18] The acy-
lation depicted in Scheme 1 was initially investigated
as a model reaction (dimethyl maleate 2a was used in
place of diethyl maleate II; Table 1).
Scheme 1. a) Flow TBADT-photocatalyzed reaction of hep-
tanal I with diethyl maleate II. b) Mechanism of the reac-
tion. V=reactor volume.
Thus, circulation of a solution containing an equi-
a 125 W medium pressure Hg vapor lamp.[12] As an molar amount (0.1M) of 1a and 2a through the pho-
example, succinate III was obtained in a 67% isolated toreactor at a rate corresponding to a residence time
yield starting from heptanal I and diethyl maleate II of 100 min (0.5 mLminÀ1) resulted in a complete con-
(Scheme 1a). The reaction was promoted by excited version of the starting substrates. The yield of keto
decatungstate, prone to abstract a hydrogen atom ester 3 was almost quantitative, but decreased to 73%
from the formyl group in I. The so-formed acyl radi- when increasing the flow rate to 0.6 mLminÀ1
cal then added to II to give a radical adduct that in (Table 1, entries 1 and 2). Compound 3 was likewise
turn regenerated the reduced catalyst via a back hy- formed in a satisfactory yield (up to 79%) when
drogen-atom transfer reaction, while giving the de- a higher concentration of both substrates was adopted
sired product III (Scheme 1b). Actually, the same re- (up to 0.5M, flow rate=0.5 mLminÀ1, entries 3 and
action carried out in a quartz test tube under batch 4), whereas an incomplete consumption of the re-
conditions by means of the same medium pressure Hg agents was observed when using 1M reagents
vapor lamp, but equipped with a merry-go-round ap- (entry 5). This drawback can be overcome by increas-
paratus, gave product III in almost the same yield ing the reaction time to 125 min (0.4 mLminÀ1 flow
(66%).[12] Under flow conditions, however, the reac- rate), but the resulting yield was unsatisfactory (60%,
tion time was shorter (2 vs. 6 h) and the space time entry 6).
yield parameter (STY, 67 mmolLÀ1 hÀ1) was higher
With such positive results in hand, we tested our
with respect to batch conditions (11 mmolLÀ1 hÀ1), experimental set-up investigating the photocatalyzed
À
À
albeit a comparable “specific productivity” (mmol of formation of C C and C N bonds by using aldehydes
product formed with respect to the energy con- as hydrogen donors as summarized in Table 2. In each
sumed)[13] resulted. A flow system capable to maintain case, a preliminary optimization was carried out to
the same reaction time and markedly improve the find the maximum concentration of reagents allowing
amount of product formed, while limiting the use of us to achieve a complete consumption, while main-
electricity, is thus desirable.
taining the highest flow rate (never exceeding
To this aim, we assembled an upgraded flow photo- 0.5 mLminÀ1). In order to assess the waste production
reactor consisting in coils of UV-transparent FEP of each process, the values of the process mass inten-
tubing (fluorinated ethylene propylene; outer diame- sity parameter (PMI; defined as the total amount of
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Decatungstate Photocatalyzed Acylations and Alkylations in Flow
Scheme 2. TBADT-photocatalyzed reactions in flow (see Figure S1 in the Supporting Information for a picture of the photo-
reactor used).
Table 1. Optimization of the photocatalyzed addition of hep- none 8, the radiation emitted by the lamp was Pyrex-
tanal (1a) onto dimethyl maleate (2a) by using a 500W
medium pressure Hg vapor lamp and flow photoreactor.
filtered due to competitive absorption by cyclohexe-
none (2f) at the wavelength used.
À
Finally, the formation of a C N bond under flow
Entry 1a, 2a conc. (M) Residence time (min), 3 Yield
conditions to give hydrazine derivative 13 was at-
tempted, using diisopropyl azodicarboxylate 2g as the
reaction partner. Indeed, the optimized conditions al-
lowed the use of 1a and 2g, both 0.5M, similarly to
what was observed for the synthesis of 3. Thus, the
green metrics parameters for the synthesis of keto
ester 3 were the best in the series thanks to the high
concentration of the reagents used in an equimolar
amount (PMI ca. 9 kgkgÀ1, STY> 200 mmolLÀ1 hÀ1)
with the highest flow rate tested (0.5 mLminÀ1). The
greenness of the acylation reaction, however, de-
creased in the other cases (compounds 4–12) due to
the lower amount of reagents used, the only exception
Flow rate (mLminÀ1)
[%]
1
2
3
4
5
6
0.1
0.1
0.2
0.5
1.0
1.0
100, 0.5
83, 0.6
100, 0.5
100, 0.5
100, 0.5
125, 0.4
95
73
78
79
70[a]
60
[a]
Yield based on 84% 1a consumption; traces of dimethyl
maleate were likewise observed.
materials involved in the production of the unit mass being the acylation of 2g. In the latter case, the high
of target product)[21] have been calculated and are re- reactivity of 2g probably alleviated its competitive ab-
ported in Table 2. The role of the energy expenditure sorption with TBADT at the wavelength used. Ac-
was likewise evaluated by means of the “specific pro- tually, the formation of 13 has the second best green
ductivity” parameter (vide supra).[3] Selected alde- performance
(PMI=9.85 kgkgÀ1
and
STY=
hydes, whether aliphatic (heptanal, 1a, and 3-phenyl- 183 mmolLÀ1 hÀ1).
propanal, 1b) or aromatic (4-methoxybenzaldehyde, We then moved to other hydrogen donors (1d–m;
1c), were investigated. In all cases, the reaction with see Table 3), such as amides, ethers, 1,3-benzodiox-
different electron-poor partners gave the desired acy- oles, nitriles, alkylbenzenes and alkanes. In the case of
lated derivatives (3–12) in moderate to good yields, amides (1d, 1e), a 4 equiv. excess of the hydrogen
demonstrating that the assembled flow photoreactor donor R-H was required in order to achieve a satisfac-
is suitable for TBADT photocatalyzed acylation reac- tory yield, and this resulted in calculated PMI values
tions.
up to 68.63 kgkgÀ1 (entries 1–3). A comparable excess
When required, a slight excess of one of the sub- amount of ethers 1f–1h (from 3 to 4 times the con-
strates was employed to maximize the overall yield. centration of the electron-poor olefin) was needed for
Furthermore, in the preparation of b-acylcyclohexa- the synthesis of compounds 17–20 (entries 4–7). In
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Table 2. Flow photocatalyzed acylation of compounds 2a–g.[a]
[a]
A solution (50 mL) of substrates 1, 2 and TBADT (2”10À3 M, 0.4-2 mol%) in MeCN was
irradiated in a photochemical flow apparatus (see text). The conditions reported in the
Table have been optimized in terms of substrate concentration and flow rate (see the Sup-
porting Information for a detailed description of the conditions).
[b]
Number of mmol of product obtained with respect to the energy required for lamp opera-
tion (Wh).
Pyrex-filtered radiation was used.
[c]
contrast, 1,3-benzodioxole 1i, a better H-donor,[16a] showed excellent PMI and specific productivity values
was used in a nearly stoichiometric amount (0.22M, due to the high reactivity of azodicarboxylate 2g that
1.1 equiv.; entry 8). The reaction of THF with 2g allowed again its use in a 0.5M amount (entry 9). By
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Decatungstate Photocatalyzed Acylations and Alkylations in Flow
Table 3. Flow photocatalyzed synthesis of compounds 14–27.[a]
[a]
[b]
A solution (50 mL) of substrates 1, 2 and TBADT (2”10À3 M, 0.4–2 mol%) in MeCN (for the synthe-
sis of 14–23, 26–27) or in a 0.5M LiClO4 MeCN-H2O 5/1 mixture (for the synthesis of 24–25) was ir-
radiated in a photochemical flow apparatus (see text). The conditions reported in the Table have
been optimized in terms of substrate concentration and flow rate (see the Supporting Information for
a detailed description of the conditions).
Number of mmol of product obtained with respect to the energy required for lamp operation (Wh).
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Table 4. Comparison between flow and batch processes in decatungstate-photocatalyzed reactions.
[a]
Flow 1: Flow reactor presented here (V=50 mL; inner diameter=2.1 mm; lamp power=
500W). Flow 2: Flow reactor (V=12 mL; inner diameter=1.3 mm; lamp power=125W); see
ref.[12] Batch 1: Irradiation carried out in a multi-lamp reactor (Rayonet) equipped with 10”
15W Hg vapor lamps, lem =310 nm. Batch 2: Irradiation carried out in an immersion well appa-
ratus equipped with a 125W medium pressure Hg vapor lamps. Batch Solar: Irradiation carried
out by exposing a Pyrex vessel to natural sunlight (8 h of irradiation per day); see Ref.[16c]
[b]
No external energy needed.
contrast, poor results were obtained when aliphatic ergetic sustainability. The most relevant issues have
nitrile 1j, alkylbenzenes 1k, l and alkane 1m were em- been summarized below and revised in view of the re-
ployed as H-donors (all used in a 5-fold excess sults obtained in the present work.
amount), since the concentration of the olefin could
The performance of the photoreactor assembled in
not exceed 0.1M (entries 10–14). The flow rate adopt- the present work (Flow 1 in Table 4; volume=50 mL,
ed with alkylbenzenes was the lowest in the series 500W Hg lamp as the light source) and of that previ-
(0.2 mLminÀ1). The PMI values, as well as the other ously proposed by our group[12] (Flow 2; volume=
calculated parameters (STY, specific productivity) in 12 mL, 125W Hg lamp as the light source, see
the reactions involving 1k–m, were likewise the worst Scheme 1 and the Supporting Information for further
in the series.
details) has been compared to that obtained by a vari-
ety of batch reactors for selected processes and the
calculated parameters (the above reported PMI, STY,
yield, specific productivity and also productivity, ex-
pressed as grams of products per day) are reported in
Discussion
Whereas the advantages of using flow reactors in Table 4. In particular, to further strengthen the com-
thermal processes have been widely evidenced in the parison, purposely designed batch experiments have
literature,[7] the use of flow photochemical reactors been performed. 300 mL of solution divided in 20
and their alleged superiority over batch systems has quartz tubes (15 mL each) were irradiated in a multi-
been recently debated from different perspectives, in- lamp reactor (Rayonet; Batch 1 in Table 4), adopting
cluding productivity, as well as environmental and en- 10 phosphor-coated Hg lamps (15W each; irradiation
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Decatungstate Photocatalyzed Acylations and Alkylations in Flow
centered at 310 nm) as the light source. Furthermore,
As predictable, however, the production of waste is
in selected cases (viz. for the synthesis of compounds dominated by the (huge) amount of solvent used, that
3 and 27), 50 mL of solution (the same volume as in often represents more than 90% of the chemical
Flow 1) were irradiated in an immersion well appara- mass. Thus, a strong reduction of PMI values was ob-
tus equipped with a 125W Hg vapor lamp (Batch 2 in served when aldehydes were employed as H-donors
Table 4). The comparison likewise included selected (compare the PMI values calculated for the synthesis
batch reactions previously carried out by our group of 3). Interestingly, a similar environmental per-
under direct solar light irradiation (Batch Solar in formance can be obtained by using an immersion well
Table 4).[16c]
photochemical apparatus as the batch reactor. Analo-
gous results were obtained with amides and ethers, al-
though in this case the lower reactivity of these sub-
strates towards H-abstraction required the use of
a more diluted solution and a less favorable stoichio-
Productivity and Space Time Yield
Stephenson and co-workers recently highlighted the metric ratio had to be used. In contrast, no substantial
capability of flow microreactors to improve signifi- PMI improvement is expected without an actual in-
cantly (more than 50 times) the productivity of sever- crease in the concentration of the substrates, as in the
al visible light photoredox-catalyzed processes.[22]
A
case of poorly reactive alkanes and alkylbenzenes.[9,26]
shortening of the residence time (which resulted in an
improvement of the productivity) was also observed
by Schuster and Wipf, who compared the efficiency Energetic Expenditure
obtained when several photochemical and photocata-
lyzed reactions were carried out in either batch or Recently, Zeitler and co-workers reported a compari-
flow photoreactors.[23] The data reported herein fur- son among the performances of batch, meso- and
ther demonstrate the potential of the present meso- micro-flow reactors in the organocatalytic photoredox
scale flow reactor in the optimization of decatungstate a-alkylation of aldehydes.[4d] They demonstrated the
photocatalyzed processes. The use of a high power Hg superiority of the meso-scale reactor, simply assem-
vapor lamp, as well as the short optical path, allowed bled by coiling a polyfluorinated tubing around the
for a significant increase of the productivity in the light source (a compact fluorescent lamp).[4d] By con-
case of C- and N-acylation processes (from nearly 5 trast, no significant advancement has been observed
up to 63 times in the synthesis of 3) over the corre- when moving to microreactors.[12,13]
sponding batch processes (see Table 4). An analogous
In the present work, the use of a meso-scale flow
advantage of the in flow approach was observed when photoreactor is a winning strategy for the improve-
amides and ethers were involved. Vice versa, when ment of the specific productivity in acylation process-
poorly reactive compounds such as alkanes and alkyl- es (see Table 2 and Table 4), with a minimization of
benzenes were used, the productivity was not signifi- the required energy supply compared to batch condi-
cantly improved when using flow conditions. Indeed, tions. Of course, the use of sunlight as the irradiation
the use of a batch reactor sometimes was slightly ad- source represents an intrinsic advantage, although
vantageous in terms of yield (compare the results ob- poor STY and productivity are obtained. By contrast,
tained for the batch and flow syntheses of 25). As for only a weak or even negligible effect can be observed
sunlight-induced processes, the discontinuous nature when reactions different from acylations are consid-
of this renewable light source limited the productivity ered.
(see the Batch Solar syntheses of 3 and 27). It is also
We attempted to represent graphically these trends
worth noting that the use of flow conditions always by having recourse to radar charts, where five differ-
improves STY values with respect to batch conditions, ent indexes have been reported (yield, productivity,
due to the lower residence time (see Table 4).
PMI, specific productivity and STY). The different re-
action conditions have been ranked with respect to
each other, where a small figure represents a poor
performance and vice versa. Accordingly, the larger is
the area covered by a reaction set-up, the better is its
Production of Waste
Although the PMI value (and, as a consequence the (environmental) performance, although this criterion
E-factor, defined as PMIÀ1) has been reported to de- has only a qualitative and not a quantitative indica-
crease when moving to flow reactors under thermal tion. The paradigmatic cases of the syntheses of 3
conditions,[24] only little information is available on (dramatic improvement when shifting from batch to
the environmental performance of photochemical flow systems) and 27 (almost no improvement) are re-
processes (which also depends on the experimental ported in Figure 1.
setup, e.g., light source, geometric aspects, etc.).[16d,25]
As hinted above, solar-induced reactions, where no
energy is used for lamp operation, offer the best per-
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Conclusions
In the present paper we have demonstrated that
a meso-scale flow photoreactor is a suitable tool for
the improvement of photocatalyzed radical conjugate
addition via direct hydrogen atom transfer (HAT) re-
actions. The use of a continuous flow approach in-
volved a strong decrease of the residence time and an
increase of the productivity and STY values with re-
spect to those calculated for the corresponding batch
processes. The concentrations of the substrates can be
often increased under flow conditions, leading to an
improvement of the sustainability of the process (with
a PMI value below 10 kgkgÀ1, that is a satisfactory
value in fine chemicals production).[27] By contrast,
when higher concentrations are not allowed, shifting
from batch to flow conditions offers only limited ad-
vantages.
Experimental Section
Typical Procedure for the Synthesis of Compounds 3–
27
Hydrogen donors 1a–m and electron-poor olefins 2a–f, h–j
or azodicarboxylate ester 2g (see Tables 1–3 and the Sup-
porting Information for further details on the employed
amounts) in the presence of a catalytic amount of TBADT
(0.1 mmol, 2”10À3 M) were dissolved in 50 mL of acetoni-
trile (in the case of 1a–j, 1m) or in a 0.5M LiClO4 MeCN-
H2O 5/1 mixture (for 1k and 1l). The solution was charged
in a flask and pumped through the apparatus described in
the text (see also the Supporting Information, Figure S1).
The final solution was evaporated and the residue was puri-
fied by column chromatography (cyclohexane:ethyl acetate
as the eluents).
Figure 1. Radar charts for the synthesis of: a) 3 and b) 27.
For the meaning of the parameters, see text and Table 4.
formance in terms of specific productivity. By con-
trast, these reactions suffer from a poor overall pro-
ductivity as a result of the discontinuous nature of
Acknowledgements
We thank Prof. A. Albini and M. Mella (University of Pavia)
this light source (only 8 h per day can be actually ex- for fruitful discussions.
ploited). The calculated PMI values are governed by
the yield and the concentration of the substrates,
where flow approaches offer an actual advantage only
if a concentration increase is possible (e.g., in the syn-
References
thesis of 3, but not in that of 27).
[1] a) S. V. Luis, E. Garcia-Verdugo, (Eds.), Chemical Re-
actions and Processes Under Flow Conditions; RSC
Publishing: Cambridge and London, 2009; b) D. Webb,
T. F. Jamison, Chem. Sci. 2010, 1, 675–680; c) J.
Wegner, S. Ceylan, A. Kirschning, Adv. Synth. Catal.
2012, 354, 17–57; d) J. C. Pastre, D. L. Browne, S. V.
Ley, Chem. Soc. Rev. 2013, 42, 8849–8869; e) L. Carroc-
cia, B. Musio, L. Degennaro, G. Romanazzi, R. Luisi, J.
Flow Chem. 2013, 3, 29–33; f) Flow Chemistry, (Eds.: F.
Darvas, G. Dorman, V. Hessel), De Gruyter, 2014;
g) M. Brzozowski, M. OꢀBrien, S. V. Ley, A. Polyzos,
Acc. Chem. Res. 2015, 48, 349–362; h) F. G. Finelli,
A final remark deals with the different per-
formance offered by the flow reactor presented here
(Flow 1; V=50 mL; inner diameter=2.1 mm; lamp
power=500W) with respect to that previously report-
ed by our group (Flow 2; V=12 mL; inner diame-
ter=1.3 mm; lamp power=125W). As apparent from
Figure 1a, the updated version outperforms the previ-
ous one in all of the indexes considered.
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UPDATES
Decatungstate Photocatalyzed Acylations and Alkylations in Flow
L. S. M. Miranda, R. O. M. A. de Souza, Chem.
Commun. 2015, 51, 3708–3722.
[2] J. P. Knowles, L. D. Elliott, K. I. Booker-Milburn, Beil-
[12] M. Fagnoni, F. Bonassi, A. Palmieri, S. Protti, D. Ravel-
li, R. Ballini, Adv. Synth. Catal. 2014, 356, 753–758.
[13] D. Ravelli, S. Protti, M. Fagnoni, A. Albini, Curr. Org.
Chem. 2013, 17, 2366–2373.
stein J. Org. Chem. 2012, 8, 2025–2052.
[3] A. Albini, L. Germani, in: Handbook of Synthetic Pho-
tochemistry. (Eds.: A. Albini, M. Fagnoni) Wiley-VCH,
Weinheim, 2010, pp 1–24.
[14] a) S. Esposti, D. Dondi, M. Fagnoni, A. Albini, Angew.
Chem. 2007, 119, 2583–2586; Angew. Chem. Int. Ed.
2007, 46, 2531–2534; b) D. Ravelli, M. Zema, M. Mella,
M. Fagnoni, A. Albini, Org. Biomol. Chem. 2010, 8,
4158–4164.
[15] S. Angioni, D. Ravelli, D. Emma, D. Dondi, M. Fagno-
ni, A. Albini, Adv. Synth. Catal. 2008, 350, 2209–2214.
[16] a) D. Ravelli, A. Albini, M. Fagnoni, Chem. Eur. J.
2011, 17, 572–579; b) D. Ravelli, M. Zoccolillo, M.
Mella, M. Fagnoni, Adv. Synth. Catal. 2014, 356, 2781–
2786; c) S. Protti, D. Ravelli, M. Fagnoni, A. Albini,
Chem. Commun. 2009, 7351–7353; d) M. D. Tzirakis,
M. Orfanopoulos, Angew. Chem. 2010, 122, 6027–6029;
Angew. Chem. Int. Ed. 2010, 49, 5891–5893.
[4] a) M. Oelgemçller, O. Shvydkiv, Molecules 2011, 16,
7522–7550; b) O. Shvydkiv, M. Oelgemçller, in: CRC
Handbook of Organic Photochemistry and Photobiolo-
gy, (Eds.: A. Griesbeck, M. Oelgemoeller, F. Ghetti),
3rd edn., CRC Press, 2012, pp 49–72; c) M. Oelgemoel-
ler, Chem. Eng. Technol. 2012, 35, 1144–1152; d) M.
Neumann, K. Zeitler, Org. Lett. 2012, 14, 2658–2661.
[5] Y. Su, N. J. W. Straathof, V. Hessel, T. Nol, Chem. Eur.
J. 2014, 20, 10562–10589.
[6] Z. J. Garlets, J. D. Nguyen, C. R. J. Stephenson, Isr. J.
Chem. 2014, 54, 351–360.
[7] For reviews on synthetic applications of flow chemistry,
see: a) J. Wegner, S. Ceylan, A. Kirschning, Adv. Synth.
Catal. 2012, 354, 17–57; b) J. C. Pastre, D. L. Browne,
S. V. Ley, Chem. Soc. Rev. 2013, 42, 8849–8869; c) D.
Webb, T. F. Jamison, Chem. Sci. 2010, 1, 675–680;
d) B. J. Deadman, S. G. Collins, A. R. Maguire, Chem.
Eur. J. 2015, 21, 2298–2308; e) V. Hessel, D. Kralisch,
N. Kockmann, T. Nol, Q. Wang, ChemSusChem 2013,
6, 746–789.
[8] B. D. A. Hook, W. Dohle, P. R. Hirst, M. Pickworth,
M. B. Berry, K. I. Booker-Milburn, J. Org. Chem. 2005,
70, 7558–7564.
[9] L. D. Elliott, J. P. Knowles, P. J. Koovits, K. G. Maskill,
M. J. Ralph, G. Lejeune, L. J. Edwards, R. I. Robinson,
I. R. Clemens, B. Cox, D. D. Pascoe, G. Koch, M.
Eberle, M. B. Berry, K. I. Booker-Milburn, Chem. Eur.
J. 2014, 20, 15226–15232.
[10] a) S. Protti, M. Fagnoni, D. Ravelli, ChemCatChem
2015, 7, 1516–1523; b) M. Fagnoni, D. Dondi, D. Ravel-
li, A. Albini, Chem. Rev. 2007, 107, 2725–2756.
[11] a) I. N. Lykakis, E. Evgenidou, M. Orfanopoulos, Curr.
Org. Chem. 2012, 16, 2400–2414; b) M. D. Tzirakis, I. N.
Lykakis, M. Orfanopoulos, Chem. Soc. Rev. 2009, 38,
2609–2621; c) C. Tanielian, Coord. Chem. Rev. 1998,
178–180, 1165–1181.
[17] K. Yamada, M. Okada, T. Fukuyama, D. Ravelli, M.
Fagnoni, I. Ryu, Org. Lett. 2015, 17, 1292–1295.
[18] H. Qrareya, D. Ravelli, M. Fagnoni, A. Albini, Adv.
Synth. Catal. 2013, 355, 2891–2899.
[19] a) D. Dondi, M. Fagnoni, A. Albini, Chem. Eur. J.
2006, 12, 4153–4163; b) D. Dondi, D. Ravelli, M. Fag-
noni, M. Mella, A. Molinari, A. Maldotti, A. Albini,
Chem. Eur. J. 2009, 15, 7949–7957.
[20] I. Ryu, A. Tani, T. Fukuyama, D. Ravelli, S. Monta-
naro, M. Fagnoni, Org. Lett. 2013, 15, 2554–2557.
[21] C. Jimenez-Gonzalez, C. S. Ponder, Q. B. Broxterman,
J. B. Manley, Org. Process Res. Dev. 2011, 15, 912–917.
[22] J. W. Tucker, Y. Zhang, T. F. Jamison, C. R. J. Stephen-
son, Angew. Chem. Int. Ed. 2012, 51, 4144–4147.
[23] E. M. Schuster, P. Wipf, Isr. J. Chem. 2014, 54, 361–370.
[24] See for instance: a) F. Fringuelli, D. Lanari, F. Pizzo, L.
Vaccaro, Green Chem. 2010, 12, 1301–1305; b) S. Bo-
nollo, D. Lanari, J. M. Longo, L. Vaccaro, Green Chem.
2012, 14, 164–169.
[25] D. Ravelli, S. Protti, P. Neri, M. Fagnoni, A. Albini,
Green Chem. 2011, 13, 1876–1884.
[26] See, for instance: J. D. Nguyen, B. Reiß, C. Dai, C. R. J.
Stephenson, Chem. Commun. 2013, 49, 4352–4354.
[27] R. A. Sheldon, Green Chem. 2007, 9, 1273–1283.
Adv. Synth. Catal. 2015, 357, 3687 – 3695
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