UV PhotoVap: Demonstrating How a Simple and Versatile Reactor Based on a Conventional Rotary Evaporator Can Be Used for UV Photochemistry

Article abstract of DOI:10.1021/acs.oprd.8b00037

We report the use of a simple rotary evaporator as a semi-continuous UV photochemical reactor. By generation of a thin film from the rotation of a flask, better light penetration is achieved, and in this work we used high-power Hg lamps to enable the direct irradiation of molecules with UV light. The intramolecular [2 + 2] photocycloaddition of Cookson's dione and the intermolecular [2 + 2] photocycloaddition of maleimide with 1-hexyne were used as test reactions to examine the effectiveness of this reactor. High productivities, equivalent to 210 g h^-1, were obtained for the simple intramolecular reaction, demonstrating the scalability of the reactor. The effects of flask size, reaction mixture volume, and use of borosilicate or quartz glassware were also investigated.

Full text of DOI:10.1021/acs.oprd.8b00037

Subscriber access provided by UNIV OF DURHAM
UV PhotoVap: Demonstrating how a simple and versatile reactor based
on a conventional rotary evaporator can be used for UV Photochemistry
Charlotte Ann Clark, Darren Stephen Lee, Stephen J. Pickering, Martyn Poliakoff, and Michael W. George
Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/acs.oprd.8b00037 • Publication Date (Web): 28 Mar 2018
Downloaded from http://pubs.acs.org on March 28, 2018
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 10
Organic Process Research & Development
UV PhotoVap: Demonstrating how a simple and versatile reactor based on a conventional rotary
evaporator can be used for UV Photochemistry
1
2
3
4
5
6
7
Charlotte A. Clark†, Darren S. Lee†, Stephen J. Pickering‡, Martyn Poliakoff*†, and Michael W.
George*†§
8
9
†School of Chemistry, ‡Department of Mechanical, Materials and Manufacturing Engineering, The
University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom
§ Department of Chemical and Environmental Engineering, The University of Nottingham Ningbo China,
199 Taikang East Road, Ningbo 315100, China
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Email. martyn.poliakoff@nottingham.ac.uk; mike.george@nottingham.ac.uk
Abstract
We report the use of a simple rotary evaporator as a semi-continuous UV photochemical reactor. By
generating a thin film from the rotation of a flask, better light penetration is achieved and, in this report, we
have used high power Hg lamps to enable the direct irradiation of molecules using UV light. The
intramolecular [2+2] photocycloaddition of Cookson's dione and the intermolecular [2+2]
photocycloaddition of maleimide with 1-hexyne have been used as test reactions to examine the
effectiveness of this reactor. High productivities, equivalent to 210 g h-1 were obtained for the simple
intramolecular reaction, demonstrating the scalability of the reactor. The effects of flask size, reaction
mixture volume and use of borosilicate or quartz glassware have also been investigated.
1
ACS Paragon Plus Environment

Organic Process Research & Development
Page 2 of 10
Table of Contents Graphic
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2
ACS Paragon Plus Environment

Page 3 of 10
Organic Process Research & Development
Introduction
1
2
3
4
5
6
7
8
9
Photochemical processing is undergoing a renaissance1-9 and this, in part, is driven by an increasing focus on
flow and continuous processing both in academia and industry.10-21 Flow chemistry offers particular
advantages for photochemistry where limitations of light penetration makes the scale-up of batch processes
more difficult. Much of the current interest has involved visible light photochemistry, particularly in the area
of photo-redox catalysis.22-30 The increasing number of researchers working in this field has helped fuel the
demand for effective and efficient photo-reactors and new experimental approaches.313233
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Our reactors have previously employed visible LEDs22,34-40 and such light sources were also used in our
recent photo-reactor41 for conventional solvents, which is based on a rotary evaporator (we styled this the
PhotoVap) where generation of a thin film enabled better light penetration, hence increased reaction
efficiency. This reactor can be operated in a semi-continuous manner and we have demonstrated that,
despite its simplicity, it is flexible, allowing different modes of operation on multiple scales by simply
changing the size of flask. It has efficient gas-liquid mass transfer as a consequence of the large surface area
of the thin-film generated upon spinning.41
For UV photochemical flow reactions, a major innovation was reported by Berry and Booker-Milburn where
they described the construction of a reactor consisting of a coil (single or multi-layered) of fluorinated
ethylene propylene (FEP) tubing wrapped around a transparent housing containing a Hg lamp.42 Since their
initial report, this approach has been exploited by many researchers43-61 and equipment manufacturers62
around the world. Recently, they reported a new high-capacity parallel tube flow reactor (PTFR) for UV
photochemical synthesis.63 Building upon their earlier work with FEP reactors, they designed the PTFR
reactor to meet several criteria for scaling up UV photochemical processes: (i) the reactor should be capable
of delivering ≥1 kg per day; (ii) it should encapsulate the UV as effectively as in an FEP reactor; (iii) it
should have a small footprint to fit within a standard fumehood; (iv) the FEP should be replaced with a more
durable, UV transparent tubing. The reactor operates with safe containment of a high-power (1−5 kW) UV
source and has been demonstrated with reactions on a variety of scales while reducing reaction times 10-fold
compared to their previous FEP reactors.63
Our original PhotoVap report focused on using visible light to initiate photochemical reactions primarily
involving oxygen. In this paper we extend the concept of using a rotary evaporator for thin film generation
and show that this relatively simple approach has considerable potential for UV photochemistry.
3
ACS Paragon Plus Environment

Organic Process Research & Development
Page 4 of 10
Results and Discussion
1
2
3
4
5
6
7
8
9
Safety is paramount in UV photolysis experiments particularly the containment of high-power UV sources
and radiation. Our approach has been to contain the reactor within a single fume hood where the solid walls
enclose the UV radiation on three sides and the glass sash is equipped with a removable dark-red plastic
filter which provides enhanced blocking of hard UV light and most of the visible spectrum too (see ESI).
The principle of the reactor is the same as described previously for visible light but with two main
differences: i) The visible light LEDs have been replaced by high power mercury lamps (1400-2000 W per
lamp, see ESI for more details). These Hg lamps provide a broadband emission that can be used to excite a
range of different chromophores. ii) In this UV set-up, inert nitrogen gas is delivered into the reactor during
operation, with a mass flow controller to control the delivery rate. Often, the presence of oxygen has a
deleterious effect on reactions involving UV light, by quenching excited states and lowering productivity.
The operation of the reactor is as described previously; the desired volume of reaction solution is delivered
and removed using two peristaltic pumps, while the temperature and rotation speed are controlled using the
built-in rotary evaporator functions (Figure 1), with all functions under the control of a computer.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 1. A simplified schematic showing the general set-up of the UV PhotoVap; inset photograph from
above showing the air-cooled Hg lamps in position around the flask.
The two UV lamps were positioned directly facing the thin film that is formed by rotation of the flask. In
this arrangement, the water bath was used to maintain a constant temperature of the flask (all reactions were
run with the average internal temperature, during irradiation of 37 °C). For some reactions, the reactor was
4
ACS Paragon Plus Environment

Page 5 of 10
Organic Process Research & Development
operated semi-continuously, where the flask was filled, irradiated and then emptied on an automated cycle.
For each experiment, the temperature was continually monitored during irradiation by internal and external
1
2
3
4
5
thermocouples. Typically, during the course of operation, the temperature increased (at a rate of ca. 3.5 °C
min-1), with an average temperature of ca. 37 °C. Despite any increase in temperature, the amount of solvent
6
7
evaporation was found to be minimal (ca. < 2 mL).
8
9
The intramolecular [2+2] cycloaddition of tricycle (1) was explored as an initial test of the reactor. This
reaction has been shown to perform very efficiently under a range of UV irradiation wavelengths and forms
only one product 2, the so-called Cookson’s dione (Scheme 1).64-67 The simplicity of the reaction and the
ease of preparing 1 on multigram scales made this reaction a convenient benchmark for the reactor
performance.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 1. Intramolecular [2+2] cycloaddition of 1 to form Cookson’s dione (2).
Initially, 30 mL of a 0.25 M solution of 1 in EtOAc was irradiated in a 1 L quartz flask. Using a single 2 kW
Hg lamp, moderate to high conversion and yields could be obtained in less than 1 minute with 97%
conversion (90% yield) (Table 1, entries 1-3). Switching to a borosilicate reaction flask gave a drop in
productivity with twice the irradiation time needed to reach high conversions (Table 1, entry 4). Increasing
both the irradiated volume and the lamp power resulted in a noticeable increase in productivity with the
highest productivity (entry 7; 210.6 g h-1) obtained using a combination of lamps (1 × 1400 W plus 1 × 2000
W; i.e. 3.4 kW total). Although the majority of the runs were conducted with the reactor running as a batch
reactor, we obtained similar productivities (e.g. entry 8; 170.5 g h-1) when the reactor was operated semi-
continuously. This simple intramolecular reaction demonstrates that the reactor is capable of being scaled up
relatively quickly to a point where it is producing >200 g h-1. Also, given the simplicity of the reactor
design, issues that could lead to downtime, such as reactor fouling, can be easily minimized by simply
swapping the flask for a clean one.
5
ACS Paragon Plus Environment

Organic Process Research & Development
Page 6 of 10
Table 1. Comparing % conversion of 1, % yield and productivities (g h-1) of 2 over a range of reactor
1
2
parameters.
3
4
5
6
7
Entry
Lamp
Irradiated
[1] / M
Photolysis
Time / s
Conversion Yield / %
/ %
Equivalent
Productivitya /
g h-1
Power / kW Volume / mL
8
9
1
2
2.0
2.0
2.0
2.0
3.4
3.4
3.4
3.4
30
30
0.25
0.25
0.25
0.25
0.5
30
45
60
150
30
60
90
60
63
84
97
94
35
63
88
64
58
77
90
80
34
63
83
59
55.1
56.4
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3
30
46.2
4b
30
22.2
5
100
100
100
100
148
6
0.5
198.7
7
0.5
210.6
8c
0.5
170.5
Unless specified otherwise the reaction was conducted in batch in EtOAc using a 1 L round bottomed quartz flask rotating at 150 RPM with N2
bubbling through the solution (at 30 sccm)(sccm = standard cubic centimeters per minute). aEquivalent Productivity takes into account the time
to pump in and out of the vessel (Processing time) and is calculated by: [([1] (M) × Irradiated volume (mL))/1000] × yield × molecular weight ×
(3600 s/Irradiation time (s) + Processing time (s)). bReaction flask was a 1 L borosilicate round bottomed flask. cReaction conducted by running
the reactor as a semi-continuous process.
The reactor was also run using a more complex intermolecular reaction involving two components; the
[2+2] cycloaddition of maleimide (3) with 1-hexyne (4) (Scheme 2). The reaction proceeds via the
excitation of 3 which subsequently reacts with 4 in a [2+2] cycloaddition yielding the bicyclic product 5. An
added complication is that 4 is relatively volatile (b.p. 71.3 °C), allowing us to probe any possible reagent
loss during operation.
Scheme 2. [2+2] photo-cycloaddition of maleimide (3) to 1-hexyne (4) forming bicycle (5).
Moderate yields of 5 (42%) were obtained using a single 1.4 kW lamp within 2 minutes irradiation time
(Table 2, entry 1). Doubling the lamp power (Table 2, entry 2) by adding a second 1.4 kW lamp gave a
similar yield in half of the time (60 s). Changing the flask to borosilicate (Table 2, entry 3) gave a drop in
productivity of ca. 50% as expected because this glassware filters out some of the UV light. In our visible
light experiments, we observed an increase in productivity on increasing both the flask size and irradiated
solution volume, and were keen to investigate this effect for the UV.41 For this reaction, on increasing the
irradiated solution volume we observed a corresponding increase in both productivity and mass balance
6
ACS Paragon Plus Environment

Page 7 of 10
Organic Process Research & Development
(Table 2, entry 4), attributable to a reduction in the amount of polymeric byproduct formed. This was also
apparent on visual inspection of the flask where considerably less reactor fouling observed when a larger
irradiation volume was used. The use of larger volumes is expected to increase the amount of mixing and
reduce the potential for over-irradiation.
1
2
3
4
5
6
7
8
9
Clearly this reaction suffers from some secondary irradiation or competing processes when quartz is used as
the reaction glassware, because the conversion is quite high but the yield is roughly half that with
borosilicate. Additional experiments with an excess (5 and 10 equiv.) of 1-hexyne (Table 2, entries 5 and 6),
showed little increase in the yield compared to that with 1.5 equiv. (Table 2, entry 2) which suggests that
any evaporation of this reagent is minimal despite its volatility and low boiling point (71.3 °C).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 2. Photo [2+2] cycloaddition of 3 with 1-hexyne to form 4 using various parameters in the reactor.
Entry
Lamp Power
/ kW
Irradiated
Photolysis
Time / s
Mass
Conversion Yield / %
/ %
Equivalent
Volume / mL
balance /
Productivitya /
%
52
46
79
80
54
51
g h-1
1
2
1.4
2.8
2.8
2.8
2.8
2.8
30
30
120
60
60
60
60
60
81
83
25
29
82
79
42
38
20
23
44
40
5.7
9.0
3b
30
4.7
4
100
30
14.0
10.6
9.4
5c
6d
30
Unless specified otherwise the reaction was conducted running the reactor semi-continuously. All reactions were ran in CH3CN using a 1 L
round bottomed quartz flask rotating at 150 RPM with N2 bubbling through the solution (at 30 sccm)(sccm = standard cubic centimeters per
minute). aEquivalent Productivity takes into account the time to pump in and out of the vessel (Processing time) and is calculated by: [([1] (M) ×
b
Irradiated volume (mL))/1000] × yield × molecular weight × (3600 s/Irradiation time (s) + Processing time (s)) Reaction flask was a 1 L
borosilicate round bottomed flask. Reaction conducted using c5 and d10 equivalents of 1-hexyne.
It was reasoned that a UV cutoff at ca. 250 nm might allow optimum irradiation for this reaction; therefore
we tried using an internal UV filter by simply replacing the CH3CN solvent with EtOAc (UV cutoff < 256
nm). However, repeating the reaction in EtOAc gave similar results to those reactions conducted in CH3CN.
Several external filters were also applied, this time by using the thin film that is generated on the outside of
the flask as it rotates in the water bath. Aqueous CuSO4 and KI were used with minimal improvements in
productivity (see ESI for further details). An alternative set-up was also tried with this reaction, one that
placed a 2 kW lamp above the flask. However the productivity obtained from this set-up was lower, with
lower yields and more issues with fouling/overheating. (See ESI for further details). Whilst the yields for
this reaction were typically lower than other reactors reported, this reaction is very challenging with many
possibilities for by-product formation and fouling; however productivities of up to 14.0 g h-1 were obtained
further demonstrating the potential of the reactor for scalable UV photochemistry.
7
ACS Paragon Plus Environment

Organic Process Research & Development
Page 8 of 10
1
2
3
4
5
6
7
Conclusion
In this report we have demonstrated that a simple rotary evaporator can be converted into an effective UV
photochemical reactor, by addition of high power UV lamps, which is capable of producing up to 210 g h-1.
Two reactions were studied to enable different properties of the reactor to be studied; for the simple
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
intramolecular reaction of 1
→ 2 high productivities were obtained. For the more complex intermolecular
reaction of 3 + 4 → 5, the yields were moderate owing to the possible over-irradiation of the products and
starting materials. During operation, no evidence for the evaporation of volatile reagents was observed,
suggesting that the heat generated by the lamps can be effectively managed using the water bath. The
simplicity of the design and availability of the equipment makes this a viable and inexpensive option for
anybody seeking the rapid scale up of a UV photochemical process.
Acknowledgements
We thank EPSRC grants, (EP/P013341/1) and the University of Nottingham EPSRC Impact Acceleration
fund (EP/K503800/1) for supporting this work. We also thank M. Dellar, C. Dixon, P. Fields, M. Guyler, D.
Lichfield, M. McAdam, R. Wilson and R. Meehan for technical support at the University of Nottingham
Supporting Information
Further details of the reactor, processing times, properties of the lamps and screens used, experimental
details, and the 1H and 13C NMR assignments and spectra for the compounds are provided in the ESI.
8
ACS Paragon Plus Environment

Page 9 of 10
Organic Process Research & Development
References
1
2
3
4
5
6
7
8
9
1.
2.
3.
4.
5.
6.
7.
8.
9.
Skubi, K. L.; Blum, T. R.; Yoon, T. P. Chem. Rev. 2016, 116, 10035-10074.
Romero, N. A.; Nicewicz, D. A. Chem. Rev. 2016, 116, 10075-10166.
Remy, R.; Bochet, C. G. Chem. Rev. 2016, 116, 9816-9849.
Ravelli, D.; Protti, S.; Fagnoni, M. Chem. Rev. 2016, 116, 9850-9913.
Kärkäs, M. D.; Porco, J. A.; Stephenson, C. R. J. Chem. Rev. 2016, 116, 9683-9747.
Hone, C. A.; Roberge, D. M.; Kappe, C. O. Chem. Sus. Chem. 2016, 10, 32-41.
Ghogare, A. A.; Greer, A. Chem. Rev. 2016, 116, 9994-10034.
Chen, M.; Zhong, M. J.; Johnson, J. A. Chem. Rev. 2016, 116, 10167-10211.
Cambie, D.; Bottecchia, C.; Straathof, N. J. W.; Hessel, V.; Noel, T. Chem. Rev. 2016, 116, 10276-
10341.
Plutschack, M. B.; Pieber, B.; Gilmore, K.; Seeberger, P. H. Chem. Rev. 2017, 117, 11796-11893.
Koenig, S. G.; Sneddon, H. F. Green Chem. 2017, 19, 1418-1419.
Britton, J.; Raston, C. L. Chem. Soc. Rev. 2017, 46, 1250-1271.
Porta, R.; Benaglia, M.; Puglisi, A. Org. Process Res. Dev. 2016, 20, 2-25.
Gutmann, B.; Cantillo, D.; Kappe, C. O. Angew. Chem. Int. Ed. 2015, 54, 6688-6728.
Baumann, M.; Baxendale, I. R. Beilstein J. Org. Chem. 2015, 11, 1194-1219.
Pastre, J. C.; Browne, D. L.; Ley, S. V. Chem. Soc. Rev. 2013, 42, 8849-8869.
Baxendale, I. R. J. Chem. Technol. Biot. 2013, 88, 519-552.
Wegner, J.; Ceylan, S.; Kirschning, A. Adv. Synth. Catal. 2012, 354, 17-57.
Hartman, R. L.; McMullen, J. P.; Jensen, K. F. Angew. Chem. Int. Ed. 2011, 50, 7502-7519.
Webb, D.; Jamison, T. F. Chem. Sci. 2010, 1, 675-680.
Mak, X. Y.; Laurino, P.; Seeberger, P. H. Beilstein J. Org. Chem. 2009, 5,
19. doi:10.3762/bjoc.5.19.
Wu, L.; Abada, Z.; Lee, D. S.; Poliakoff, M.; George, M. W. Tetrahedron 2017, DOI:
10.1016/j.tet.2017.11.048.
Tay, N. E. S.; Nicewicz, D. A. J. Am. Chem. Soc. 2017, 139, 16100-16104.
Seo, H.; Liu, A. F.; Jamison, T. F. J. Am. Chem. Soc. 2017, 139, 13969-13972.
Pitzer, L.; Sandfort, F.; Strieth-Kalthoff, F.; Glorius, F. J. Am. Chem. Soc. 2017, 139, 13652-13655.
Ma, J.; Rosales, A. R.; Huang, X.; Harms, K.; Riedel, R.; Wiest, O.; Meggers, E. J. Am. Chem. Soc.
2017, 139, 17245-17248.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
Loh, Y. Y.; Nagao, K.; Hoover, A. J.; Hesk, D.; Rivera, N. R.; Colletti, S. L.; Davies, I. W.;
MacMillan, D. W. C. Science 2017, 358, 1182-1187.
Dauncey, E. M.; Morcillo, S. P.; Douglas, J. J.; Sheikh, N. S.; Leonori, D. Angew. Chem. Int. Ed.
2017, DOI: 10.1002/anie.201710790.
Chen, K.; Berg, N.; Gschwind, R.; König, B. J. Am. Chem. Soc. 2017.
Ahn, J. M.; Peters, J. C.; Fu, G. C. J. Am. Chem. Soc. 2017, DOI: 10.1021/jacs.7b10907.
29.
30.
31.
32.
Shvydkiv, O.; Limburg, C.; Nolan, K.; Oelgemöller, M. J. Flow Chem. 2012,
Ioannou, G. I.; Montagnon, T.; Kalaitzakis, D.; Pergantis, S. A.; Vassilikogiannakis, G.
ChemPhotoChem 2017, , 173-177.
Kouridaki, A.; Huvaere, K. React. Chem. Eng. 2017,
Penders, I. G. T. M.; Amara, Z.; Horvath, R.; Rossen, K.; Poliakoff, M.; George, M. W. RSC Adv.
2015, , 6501-6504.
Amara, Z.; Bellamy, J. F. B.; Horvath, R.; Miller, S. J.; Beeby, A.; Burgard, A.; Rossen, K.;
Poliakoff, M.; George, M. W. Nat. Chem. 2015, , 489-495.
2, 52-55.
1
33.
34.
2, 590-597.
5
35.
36.
7
Hall, J. F. B.; Bourne, R. A.; Han, X.; Earley, J. H.; Poliakoff, M.; George, M. W. Green Chem.
2013, 15, 177-180.
Han, X.; Bourne, R. A.; Poliakoff, M.; George, M. W. Chem. Sci. 2011, 2, 1059-1067.
37.
38.
39.
40.
Han, X.; Bourne, R. A.; Poliakoff, M.; George, M. W. Green Chem. 2009, 11, 1787-1792.
Bourne, R. A.; Han, X.; Poliakoff, M.; George, M. W. Angew, Chem. Int. Ed. 2009, 48, 5322-5325.
Bourne, R. A.; Han, X.; Chapman, A. O.; Arrowsmith, N. J.; Kawanami, H.; Poliakoff, M.; George,
M. W. Chem. Commun. 2008, 4457-4459.
9
ACS Paragon Plus Environment

Organic Process Research & Development
Page 10 of 10
41.
42.
43.
Clark, C. A.; Lee, D. S.; Pickering, S. J.; Poliakoff, M.; George, M. W. Org. Process Res. Dev. 2016,
20, 1792-1798.
Hook, B. D. A.; Dohle, W.; Hirst, P. R.; Pickworth, M.; Berry, M. B.; Booker-Milburn, K. I. J. Org.
Chem. 2005, 70, 7558-7564.
Blanco-Ania, D.; Gawade, S. A.; Zwinkels, L. J. L.; Maartense, L.; Bolster, M. G.; Benningshof, J.
C. J.; Rutjes, F. P. J. T. Org. Process Res. Dev. 2016, 20, 409-413.
Junkers, T. Eur Polym J 2015, 62, 273-280.
Halperin, S. D.; Kwon, D.; Holmes, M.; Regalado, E. L.; Campeau, L. C.; DiRocco, D. A.; Britton,
R. Org. Lett. 2015, 17, 5200-5203.
1
2
3
4
5
6
7
8
44.
45.
9
46.
47.
48.
49.
Kumarasamy, E.; Raghunathan, R.; Jockusch, S.; Ugrinov, A.; Sivaguru, J. J. Am. Chem. Soc. 2014,
136, 8729-8737.
Hurevich, M.; Kandasamy, J.; Ponnappa, B. M.; Collot, M.; Kopetzki, D.; McQuade, D. T.;
Seeberger, P. H. Org. Lett. 2014, 16, 1794-1797.
Fagnoni, M.; Bonassi, F.; Palmieri, A.; Protti, S.; Ravelli, D.; Ballini, R. Adv. Synth. Catal. 2014,
356, 753-758.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Do, H. Q.; Bachman, S.; Bissember, A. C.; Peters, J. C.; Fu, G. C. J. Am. Chem. Soc. 2014, 136
2162-2167.
Cantillo, D.; de Frutos, O.; Rincon, J. A.; Mateos, C.; Kappe, C. O. J. Org. Chem. 2014, 79, 223-
,
50.
229.
51.
Wojcik, F.; O'Brien, A. G.; Gotze, S.; Seeberger, P. H.; Hartmann, L. Chem. Eur. J. 2013, 19, 3090-
3098.
Sterk, D.; Jukic, M.; Casar, Z. Org. Process Res. Dev. 2013, 17, 145-151.
Cludius-Brandt, S.; Kupracz, L.; Kirschning, A. Beilstein J. Org. Chem. 2013, 9, 1745-1750.
Yavorskyy, A.; Shvydkiv, O.; Hoffmann, N.; Nolan, K.; Oelgemöller, M. Org. Lett. 2012, 14, 4342-
4345.
Levesque, F.; Seeberger, P. H. Angew. Chem. Int. Ed. 2012, 51, 1706-1709.
Harrowven, D. C.; Mohamed, M.; Goncalves, T. P.; Whitby, R. J.; Bolien, D.; Sneddon, H. F.
Angew. Chem. Int. Ed. 2012, 51, 4405-4408.
52.
53.
54.
55.
56.
57.
58.
Andrews, R. S.; Becker, J. J.; Gagne, M. R. Angew. Chem. Int. Ed. 2012, 51, 4140-4143.
Aida, S.; Terao, K.; Nishiyama, Y.; Kakiuchi, K.; Oelgemöller, M. Tetrahedron Lett. 2012, 53
5578-5581.
,
59.
60.
61.
Levesque, F.; Seeberger, P. H. Org. Lett. 2011, 13, 5008-5011.
Gutierrez, A. C.; Jamison, T. F. Org. Lett. 2011, 13, 6414-6417.
Bou-Hamdan, F. R.; Levesque, F.; O'Brien, A. G.; Seeberger, P. H. Beilstein J. Org. Chem. 2011,
7,
1124-1129.
Fang, Y.; Tranmer, G. K. Med. Chem. Commun. 2016, 7, 720-724.
Elliott, L. D.; Berry, M.; Harji, B.; Klauber, D.; Leonard, J.; Booker-Milburn, K. I. Org. Process
Res. Dev. 2016, 20, 1806-1811.
Elliott, L. D.; Knowles, J. P.; Koovits, P. J.; Maskill, K. G.; Ralph, M. J.; Lejeune, G.; Edwards, L.
J.; Robinson, R. I.; Clemens, I. R.; Cox, B.; Pascoe, D. D.; Koch, G.; Eberle, M.; Berry, M. B.;
Booker-Milburn, K. I. Chem. Eur. J. 2014, 20, 15226-15232.
Aillet, T.; Loubiere, K.; Dechy-Cabaret, O.; Prat, L. Chem. Eng. Process 2013, 64, 38-47.
Cookson, R. C.; Crundwell, E.; Hill, R. R.; Hudec, J. J. Chem. Soc. 1964, 3062-3075.
Cookson, R. C.; Crundwell, E.; Hudec, J. Chem. Ind-London 1958, 1003-1004.
62.
63.
64.
65.
66.
67.
10
ACS Paragon Plus Environment