ACS Catalysis
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recycled. At the same time, this technology has a high potential
Author Contributions
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to assist the process chemist to safely and sustainably employee
carbene chemistry at large scale. NP catalyst used in this study
is stable, recyclable, and requires inexpensive PPh3 ligand. DLS
data supports the existence of nanomicelles in the presence of
carbenes. Further reports on the use of metal-carbenes in
micellar media for enantioselective pathways will be reported
in a due course.
The manuscript was written through contributions of all authors.
All authors have given approval to the final version of the
manuscript.
ACKNOWLEDGMENT
Financial support provided by the University of Louisville and
Novartis Institutes for Medical Research is warmly acknowledged.
EXPERIMENTAL METHODS.
REFERENCES
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Preparation of Nanocatalyst. To a vigorously stirred solution
of K2PdCl4 (33 mg, 0.1 mmol) and tetra-n-octylammonium
bromide (109 mg, 0.2 mmol) in 1:1 deionized water/CH2Cl2 (2
mL), a solution of PPh3 (131 mg, 0.5 mmol) in CH2Cl2 (2 mL)
was slowly added at room temperature (rt). The resulting
mixture was stirred for 30 minutes at rt. To the reaction mixture,
a solution of NaBH4 (12 mg, 0.3 mmol) in deionized water (1
mL) was slowly added followed by addition of 0.1 mL 3 wt %
PS-750-M in H2O. Reaction mixture was stirred for additional
1 h at rt under inert atmosphere.
(1)
(2)
(3)
Lipshutz, B. H.; Gallou, F.; Handa, S. Evolution of Solvents in
Organic Chemistry. ACS Sustain. Chem. Eng. 2016, 4, 5838–
5849.
Kitanosono, T.; Masuda, K.; Xu, P.; Kobayashi, S. Catalytic
Organic Reactions in Water toward Sustainable Society. Chem.
Rev. 2018, 118, 679–746.
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
Breslow, R. The Principles of and Reasons for Using Water as a
Solvent for Green Chemistry. Handbook of Green Chemistry.
March
2010,
15,
pp
1–29.
(4)
(5)
Lipshutz, B. H.; Isley, N. A.; Fennewald, J. C.; Slack, E. D. On
the Way Towards Greener Transition-Metal-Catalyzed Processes
as Quantified by E Factors. Angew. Chem., Int. Ed. 2013, 52,
10952–10958.
Chang, C.-R.; Huang, Z.-Q.; Li, J. The Promotional Role of
Water in Heterogeneous Catalysis: Mechanism Insights from
Computational Modeling. Wiley Interdiscip. Rev. Comput. Mol.
Sci. 2016, 6, 679–693.
After 1 h additional stirring, CH2Cl2 (1 mL) was added to the
reaction mixture and mixture was stirred for few minutes.
Stirring was stopped and organic layer was allowed to separate
from the aqueous. Organic layer was removed from the reaction
mixture. Organic layer was dried over Na2SO4. Volatiles were
removed under reduced pressure to obtain nanoparticles as
yellow solid. To the solid material 1 mL pentane was added and
material was tritiated for a minute. Pentane was removed under
reduced pressure to obtain free-flowing yellow solid (132 mg).
(6)
(7)
Sheldon, R. A. The E Factor 25 Years on: The Rise of Green
Chemistry and Sustainability. Green Chem. 2017, 19, 18–43.
Alfonsi, K.; Colberg, J.; Dunn, P. J.; Fevig, T.; Jennings, S.;
Johnson, T. A.; Kleine, H. P.; Knight, C.; Nagy, M. A.; Perry, D.
A.; Stefaniak, M. Green Chemistry Tools to Influence
Medicinal Chemistry and Research Chemistry Based
Organisation. Green Chem. 2008, 10, 31–36.
a
Catalytic Reactions with Nanocatalyst. In a 4 mL reaction
vial containing PTFE-coated stir bar, N-tosylhydrazone (0.37
mmol), aryl halide (0.25 mmol), Pd NPs (1.5 mol %, 12 mg),
and LiOH (0.5 mmol, 12 mg) were added. The reaction vial was
sealed with a rubber septum. 1.0 mL 3 wt % aq. PS-750-M was
added to the reaction mixture and septum was wrapped with
parafilm. The reaction mixture was stirred at 70 ˚C till complete
consumption of starting material.
(8)
(9)
Prat, D.; Hayler, J.; Wells, A. Merck’s Reaction Review Policy:
An Exercise in Process Safety. Green Chem. 2014, 16, 4546–
4551.
Byrne, F. P.; Jin, S.; Paggiola, G.; Petchey, T. H. M.; Clark, J. H.;
Farmer, T. J.; Hunt, A. J.; Robert McElroy, C.; Sherwood, J.
Tools and Techniques for Solvent Selection: Green Solvent
Selection Guides. Sustain. Chem. Process. 2016, 4, 7.
Leahy, D. K.; Simmons, E. M.; Hung, V.; Sweeney, J. T.;
Fleming, W. F.; Miller, M. Design and Evolution of the BMS
Process Greenness Scorecard. Green Chem. 2017, 19, 5163–
5171.
(10)
After complete consumption of starting material as monitored
by TLC and GCMS, reaction mixture was cooled to rt. 1 mL
EtOAc or MTBE was added to the reaction mixture and mixture
was stirred for a minute at rt. Stirring was stopped and organic
layer was allowed to separate from the aqueous layer. Organic
layer was removed with the use of pipette. Similarly, additional
extraction procedure was employed. Combined organic layers
were dried over anhydrous Na2SO4. Volatiles were removed
under reduced pressure to obtain semi-pure product, which was
further purified by flash chromatography using EtOAc/hexanes
as eluent. All organic solvents were recovered and reused.
(11)
(12)
Leadbeater, N. E. Fast, Easy, Clean Chemistry by Using Water as
a Solvent and Microwave Heating: The Suzuki Coupling as an
Illustration. Chem. Commun. 2005, 23, 2881–2902.
Capello, C.; Fischer, U.; Hungerbühler, K. What Is a Green
Solvent? A Comprehensive Framework for the Environmental
Assessment of Solvents. Green Chem. 2007, 9, 927–934.
Prat, D.; Hayler, J.; Wells, A. A Survey of Solvent Selection
Guides. Green Chem. 2014, 16, 4546–4551.
Kobayashi, S.; Nagayama, S.; Busujima, T. Lewis Acid Catalysts
Stable in Water. Correlation between Catalytic Activity in Water
and Hydrolysis Constants and Exchange Rate Constants for
Substitution of Inner-Sphere Water Ligands. J. Am. Chem. Soc.
1998, 120, 8287–8288.
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ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS
Publications website.
Detailed reaction optimization, general catalytic procedure,
characterization of nanomaterial, analytical data and NMRs of
compounds.
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Kobayashi, S.; Ogawa, C. New Entries to Water-Compatible
Lewis Acids. Chem. – A Eur. J. 2006, 12, 5954–5960.
Cortes-Clerget, M.; Akporji, N.; Zhou, J.; Gao, F.; Guo, P.;
Parmentier, M.; Gallou, F.; Berthon, J.-Y.; Lipshutz, B. H.
Bridging the Gap between Transition Metal- and Bio-Catalysis
via Aqueous Micellar Catalysis. Nat. Commun. 2019, 10, 2169.
Hamasaka, G.; Muto, T.; Uozumi, Y. Molecular-Architecture-
Based Administration of Catalysis in Water: Self-Assembly of an
Amphiphilic Palladium Pincer Complex. Angew. Chem., Int. Ed.
2011, 50, 4876–4878.
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AUTHOR INFORMATION
Osako, T.; Torii, K.; Hirata, S.; Uozumi, Y. Chemoselective
Continuous-Flow Hydrogenation of Aldehydes Catalyzed by
Platinum Nanoparticles Dispersed in an Amphiphilic Resin. ACS
Catal. 2017, 7, 7371–7377.
Corresponding Author.
*sachin.handa@louisville.edu
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