Organocatalysis chemistry in flow

Current Organocatalysis

Volumn 2, Issue 2, 2015, Pages 79-101

  Puglisi, Alessandra ^a   Benaglia, Maurizio ^a   Porta, Riccardo ^a   Coccia, Francesca ^a  

^a UNIVERSITY OF MILAN   (Italy)

Author keywords

Catalytic reactors; Flow chemistry; Microreactors; Organocatalysis; Photoredox catalysis; Stereoselective synthesis; Supported chiral organocatalysts

Indexed keywords

EID: 84954397400     PISSN: 22133372     EISSN: 22133380     Source Type: Journal    
DOI: 10.2174/2213337202666150513002701     Document Type: Article

References (110)

1. Roberge, D.M.; Ducry, L.; Bieler, N.; Cretton, P.; Zimmermann, B. Microreactor Technology: A revolution for the fine chemical and pharmaceutical industries? Chem. Eng. Technol., 2005, 28, 318-323.
2. Malet-Sanz, L.; Flavien, S. Continuous flow synthesis. A pharma perspective. J. Med. Chem., 2012, 55, 4062-4098.
3. Rasheed, M.; Wirth, T. Intelligent microflow: Development of self-optimizing reaction systems. Angew. Chem. Int. Ed., 2011, 50, 357-358.
4. Noël, T.; Kuhn, S.; Musacchio, A.J.; Jensen, K.F.; Buchwald, S.L. Suzuki-miyaura cross-coupling reactions in flow: Multistep synthesis enabled by a microfluidic extraction. Angew. Chem. Int. Ed., 2011, 50, 5943-5946.
5. Wegner, J.; Ceylan, S.; Kirschning, A. Ten key issues in modern flow chemistry. Chem. Commun., 2011, 47, 4583-4592.
6. Newman, S.G.; Jensen, K.F. The role of flow in green chemistry and engineering. Green Chem., 2013, 15, 1456-1472.
7. Wu, H.; Khan, M.A.; Hussain, A.S. On-line process control and process analytical technology: integration of chemical engineering practice into semiconductor and pharmaceutical industries. Chem. Eng. Commun., 2007, 194, 760-779.
8. Poechlauer, P.; Manley, J.; Broxterman, R.; Gregertsen, B.; Ride-mark, M. Continuous processing in the manufacture of active pharmaceutical ingredients and finished dosage forms: An Industry perspective. Org. Process Res. Dev., 2012, 16, 1586-1590.
9. Evans, J. A paradigm shift. Chem. Eng., 2013, 860, 32-34.
10. Hartwig, J.; Metternich, J.B.; Nikbin, N.; Kirschning, A.; Ley, S.V. Continuous flow chemistry: a discovery tool for new chemical reactivity patterns. Org. Biomol. Chem., 2014, 12, 3611-3615.
11. Wegner, J.; Ceylan, S.; Kirschning, A. Flow chemistry-a key enabling technology for (multistep) organic synthesis. Adv. Synth. Catal., 2012, 354, 17-57.
12. Dalko, P.I. Enantioselective Organocatalysis. Reactions and Experimental procedures. Ed. Wiley VCH, Weinheim, 2007.
13. List, B. Asymmetric Organocatalysis, in Topics in Current Chemistry, Ed. Springer, 2009, vol. 291.
14. Puglisi, A.; Benaglia, M.; Chiroli, V. Stereoselective organic reactions promoted by immobilized chiral catalysts in continuous flow systems. Green Chem., 2013, 15, 1790-1813.
15. Zhao, D.; Ding, K. Recent advances in asymmetric catalysis in flow. ACS Catal., 2013, 3, 928-944.
16. Tsubogo, T.; Ishiwata, T.; Kobayashi, S. Asymmetric carbon-carbon bond formation under continuous-flow conditions with chiral heterogeneous catalysts. Angew. Chem. Int. Ed., 2013, 52, 6590-6604.
17. Spaccini, R.; Liguori, L.; Punta, C.; Bjørsvik, H.-R. Organocatalyzed epoxidation of alkenes in continuous flow using a multi-jet oscillating disk reactor. ChemSusChem, 2012, 5, 261-265.
18. Minisci, F.; Gambarotti, C.; Pierini, M.; Porta, O.; Punta, C.; Recu-pero, F.; Lucarini, M.; Mugnaini, V. Molecule-induced homolysis of N-hydroxyphthalimide (NHPI) by peracids and dioxirane. A new, simple, selective aerobic radical epoxidation of aliene. Tetrahedron Lett., 2006, 47, 1421-1424.
19. Liguori, L.; Bjørsvik, H.-R. Multijet oscillating disc millireactor: A novel approach for continuous flow organic synthesis. Org. Process Res. Dev., 2011, 5, 997-1009.
20. Baker, A.; Graz, M.; Saunders, R.; Evans, G.J.S.; Kaul, S.; Wirth, T. Flow synthesis of symmetrical di-and trisulfides using phase-transfer catalysis. J. Flow Chem., 2013, 3, 118-121.
21. Knowles, J.P.; Elliott, L.D.; Booker-Milburn, K.I. Flow photo-chemistry: Old light through new windows. Beilstein J. Org. Chem., 2012, 8, 2025-2052.
22. Garlets, Z.J.; Nguyen, J.D.; Stephenson, C.R.J. The development of visible-light photoredox catalysis in flow. Isr. J. Chem., 2014, 54, 351-360.
23. Su, Y.; Straathof, N.J.W.; Hessel, V.; Noel, T. Photochemical transformations accelerated in continuous-flow reactors: Basic concepts and applications. Chem. Eur. J., 2014, 20, 10562-10589.
24. Fagnoni, M.; Bonassi, F.; Plamieri, A.; Protti, S.; Ravelli, D.; Ballini, R. Flow synthesis of substituted-lactones by consecutive photocatalytic/reductive reactions. Adv. Synth. Catal., 2014, 356, 753-758.
25. Talla, A.; Driesse, B.; Straathof, N.J.W.; Milroy, L-G.; Brunsveld, L.; Hessel, V.; Noel, T. Metal-free photocatalytic aerobic oxidation of thiols to disulfides in batch and continuous-flow. Adv. Synth. Catal., 2015, DOI: 10.1002/adsc.201401010.
26. Schroll, P.; Konig, B. Photocatalytic-oxyamination of stable enolates, silyl enol ethers, and 2-oxoalkane phosphonic esters. Eur. J. Org. Chem., 2015, 2, 309-313.
27. Fabry, D.C.; Ronge, M.A.; Rueping, M. Immobilization and continuous recycling of photoredox catalysts in ionic liquids for applications in batch reactions and flow systems: catalytic alkene iso-merization by using visible light. Chem. Eur. J., 2015, 21, 5350-5354.
28. Rueping, M.; Vila, C.; Bootwicha, T. Continuous flow organocatalytic c h functionalization and cross-dehydrogenative coupling reactions: visible light organophotocatalysis for multicomponent reactions and c c, c p bond formations. ACS Catal., 2013, 3, 1676-1680.
29. Cantillo, D.; De Frutos, O.; Rincón, J.A.; Mateos, C.; Kappe, C.O. Continuous flow trifluoromethylation of ketones by metal-free visible light photoredox catalysis. Org. Lett., 2014, 16, 896-899.
30. Ushakov, D.B.; Gilmore, K.; Kopetzki, D.; McQuade, D.T.; Seeberger, P.H. Continuous-flow oxidative cyanation of primary and secondary amines using singlet oxygen. Angew. Chem. Int. Ed., 2014, 53, 557-561.
31. Lévesque, F.; Seeberger, P.H. Continuous-flow synthesis of the anti-malaria drug artemisinin. Angew. Chem. Int. Ed., 2012, 51, 1706-1709.
32. Kopetzki, D.; Lévesque, F.; Seeberger, P.H. A continuous-flow process for the synthesis of artemisinin. Chem. Eur. J., 2013, 19, 5450-5456.
33. Bogdan, A.R.; Mason, B.P.; Sylvester, K.T.; McQuade, D.T. Improving solid-supported catalyst productivity by using simplified packed-bed microreactors. Angew. Chem. Int. Ed., 2007, 46, 1698-1701.
34. Bogdan, A.; McQuade, D.T. A biphasic oxidation of alcohols to aldehydes and ketones using a simplified packed-bed microreactor. Beilstein J. Org. Chem., 2009, 5, No. 17
35. Bortolini, O.; Cavazzini, A.; D’Ambruoso, P.; Giovannini, P.P.; Caciolli, L.; Massi, A.; Pacifico, S.; Ragno, D. Thiazolium-functionalized polystyrene monolithic microreactors for continuous-flow umpolung catalysis. Green Chem., 2013, 15, 2981-2992.
36. Xu, D.-Z.; Shi, S.; Wang, Y. Polystyrene-immobilized DABCO as a highly efficient and recyclable organocatalyst for the Knoevenagel condensation reaction. RSC Adv., 2013, 3, 23075-23079.
37. Martín, S.; Porcar, R.; Peris, E.; Burguete, M.I.; García-Verdugo, E.; Luis, S.V. Supported ionic liquid-like phases as organocatalysts for the solvent-free cyanosilylation of carbonyl compounds: from batch to continuous flow process. Green Chem., 2014, 16, 1639-1647.
38. Costantini, F.; Bula, W.P.; Salvio, R.; Huskens, J.; Gardeniers, H.J.G.E.; Reinhoudt, D.N.; Verboom, W. Nanostructure based on polymer brushes for efficient heterogeneous catalysis in microreactors. J. Am. Chem. Soc., 2009, 131, 1650-1651.
39. Munirathinam, R.; Huskens, J.; Verboom, W. Piperazine-containing, polymer brush layer as supported base catalyst in a glass microreactor. J. Flow Chem., 2014, 4, 135-139.
40. Wirth, T. Ed.; Microreactors in Organic Synthesis and Catalysis, 2008, Wiley-VCH.
41. Hessel, V. Novel process windows-gate to maximizing process intensification via flow chemistry. Chem. Eng. Technol., 2009, 32, 1655-1681.
42. Geyer, K.; Gustafson, T.; Seeberger, P.H. Developing continuous-flow microreactors as tools for synthetic chemists. Synlett., 2009, 2382-2391.
43. Wiles, C.; Watts, P. Recent advances in micro reaction technology. Chem. Commun., 2011, 47, 6512-6535.
44. Ceylan, S.; Coutable, L.; Wegner, J.; Kirschning, A. Inductive heating with magnetic materials inside flow reactors. Chem. Eur. J., 2011, 17, 1884-1893.
45. Wiles, C.; Watts, P. Continuous flow reactors: a perspective. Green Chem., 2012, 14, 38-54.
46. Rodrigues, T.; Schneider, P.; Schneider, G. Accessing new chemical entities through microfluidic systems. Angew. Chem. Int. Ed., 2014, 53, 5750-5758.
47. Odedra, A.; Seeberger, P.H. 5-(Pyrrolidin-2-yl)tetrazole-catalyzed aldol and mannich reactions: acceleration and lower catalyst loading in a continuous-flow reactor. Angew. Chem. Int. Ed., 2009, 48, 2699-2702.
48. Fritzsche, S.; Ohla, S.; Glaser, P.; Giera, D.S.; Sickert, M.; Schneider, C.; Belder, D. Asymmetric organocatalysis and analysis on a single microfluidic nanospray chip. Angew. Chem. Int. Ed., 2011, 50, 9467-9470.
49. Opalka, S.M.; Longstreet, A.R.; McQuade, D.T. Continuous proline catalysis via leaching of solid proline. Beilstein J. Org. Chem., 2011, 7, 1671-1679.
50. Carroccia, L.; Musio, B.; Degennaro, L.; Romanazzi, G.; Luisi, R. Microreactor-mediated organocatalysis: towards the development of sustainable domino reactions. J. Flow Chem., 2013, 3, 29-33.
51. Rossi, S.; Benaglia, M.; Puglisi, A.; De Filippo, C.C.; Maggini, M. Continuous-flow stereoselective synthesis in microreactors: nucleophilic additions to nitrostyrenes organocatalyzed by a chiral bifunctional catalyst. J. Flow. Chem., 2014, DOI: 10.1556/JFC-D-14-00030.
52. Rueping, M.; Bootwicha, T.; Sugiono, E. Continuous-flow catalytic asymmetric hydrogenations: Reaction optimization using FTIR inline analysis. Beilstein J. Org. Chem., 2012, 8, 300-307.
53. Solodenko, W.; Mennecke, K.; Kirschning, A. First preparation of spacer-linked cyclic neooligoaminodeoxysaccharides. Chem. Eur. J., 2002, 8, 2717-2729.
54. Sugiono, E.; Rueping, M. Continuous-flow catalytic asymmetric hydrogenations: Reaction optimization using FTIR inline analysis. Beilstein J. Org. Chem., 2013, 9, 2457-2462.
55. Nicewicz, D.; MacMillan, D.W.C. Merging photoredox catalysis with organocatalysis: The direct asymmetric alkylation of aldehydes. Science, 2008, 322, 77-80.
56. Wang, C.; Lu, Z. Catalytic enantioselective organic transformations via visible light photocatalysis. Org. Chem. Front., 2015, 2, 179-190.
57. Neumann, M.; Zeitler, K. Application of microflow conditions to visible light photoredox catalysis. Org. Lett., 2012, 14, 2658-2661.
58. McQuade, D.T.; Seeberger, P.H. Applying flow chemistry: methods, materials, and multistep synthesis. J. Org. Chem., 2013, 78, 6384-6389.
59. Mojzesova, M.; Meciarova, M.; Marti, R.; Sebesta, R. Organocatalytic oxa-diels-alder reaction of,-unsaturated ketones under non-classical conditions. New J. Chem., 2015, 39, 2573-2579.
60. Mascia, S.; Heider, P.L.; Zhang, H.; Lakerveld, R.; Benyahia, B.; Barton, P.I.; Braatz, R.D.; Cooney, C.L.; Evans, J.M.B.; Jamison, T.F.; Jensen, K.F.; Myerson, A.S.; Trout, B.L. End-to-end continuous manufacturing of pharmaceuticals: integrated synthesis, purification, and final dosage formation. Angew. Chem. Int. Ed., 2013, 52, 12359-12363.
61. De Vos, D.E.; Vankelecom, I.F.J.; Jacobs, P.A. Chiral Catalyst Immobilization and Recycling, Wiley-VCH, Weinheim, 2000.
62. Benaglia, M. Recoverable and Recyclable Catalysts, Wiley-VCH, Weinheim, 2009.
63. Trindade, A.F.; Gois, P.M.P.; Afonso, C.A.M. Recyclable stereoselective catalysts. Chem. Rev., 2009, 109, 418-514.
64. Haraguchi, N.; Itsuno, S. Polymeric Chiral Catalyst Design and Chiral Polymer Synthesis, John Wiley & Sons, 2011.
65. Ding, K.J.; Uozomi, F.J.K. Handbook of Asymmetric Heterogeneous Catalysts, Wiley-VCH, Weinheim, 2008.
66. Benaglia, M.; Puglisi, A.; Cozzi, F. Polymer supported organic catalysts. Chem. Rev., 2003, 103, 3401-3429.
67. Cozzi, F. Immobilization of organic catalysts: When, Why, and How. Adv. Synth. Catal., 2006, 348, 1367-1390.
68. Benaglia, M. Recoverable and recyclable chiral organic catalysts. New J. Chem., 2006, 30, 1525-1533.
69. Gruttadauria, M.; Giacalone, F.; Noto, R. Supported proline and proline-derivatives as recyclable organocatalysts. Chem. Soc. Rev., 2008, 37, 1666-1688.
70. Kristensen, T.E.; Hansen, T. Polymer-supported chiral organocatalysts: synthetic strategies for the road towards affordable polymeric immobilization. Eur. J. Org. Chem., 2010, 17, 3179-3204.
71. Cantillo, D.; Kappe, C.O. Immobilized transition metals as catalysts for cross-couplings in continuous flow—a critical assessment of the reaction mechanism and metal leaching. ChemCatChem, 2014, 6, 3286-3305.
72. Rodríguez-Escrich, C.; Pericàs, M.A. Organocatalysis on Tap: Enantioselective continuous flow processes mediated by solid-supported chiral organocatalysts. Eur. J. Org. Chem., 2015, 6, 1173-1188.
73. Hafez, A.M.; Taggi, A.E.; Dudding, T.; Lectka, T. Asymmetric catalysis on sequentially-linked columns. J. Am. Chem. Soc., 2001, 123, 10853-10859.
74. Song, C.E. Cinchona Alkaloids in Synthesis and Catalysis, Wiley-VCH, Weinheim, 2009.
75. Marcelli, T.; Hiemstra, H. Cinchona Alkaloids in Asymmetric Organocatalysis. Synthesis 2010, 8, 1229-1279.
76. Melchiorre, P. Cinchona-based primary amine catalysis in the asymmetric functionalization of carbonyl compounds. Angew. Chem.Int. Ed., 2012, 51, 9748-9770.
77. Duan, J.; Li, P. Asymmetric organocatalysis mediated by primary amines derived from cinchona alkaloids: recent avances. Catal. Sci. Technol., 2014, 4, 311-320.
78. Porta, R.; Benaglia, M.; Coccia, F.; Cozzi, F.; Puglisi, A. Solid supported 9-amino-9-deoxy-epi-quinine as efficient organocatalyst for stereoselective reactions in batch and under continuous flow conditions. Adv. Synth. Catal., 2015, DOI: 10.1002/adsc.2014 00821.
79. Oh, S.H.; Rho, H.S.; Lee, J.W.; Lee, J.E.; Youk, S.H.; Chin, J.; Song, C.E. A highly reactive and enantioselective bifunctional organocatalyst for the methanolytic desymmetrization of cyclic an-hydrides: prevention of catalyst aggregation. Angew. Chem. Int. Ed., 2008, 47, 7872-7875.
80. Bae, H.Y.; Song, C.E. Cinchona-based sulfonamide organocatalysts: concept, scope, and practical applications. Bull. Korean Chem. Soc., 2014, 35, 1590-1600.
81. Lee, J-W.; Mayer-Gall, T.; Opwis, K.; Song, C.E.; Gutmann, J.S.; List, B. Organotextile Catalysis. Science, 2013, 341, 1225-1229.
82. Alza, E.; Rodrígues-Escrich, C.; Sayalero, S.; Bastero, A.; Pericàs, M.A. A solid-supported organocatalyst for highly stereoselective, batch, and continuous-flow mannich reactions. Chem. Eur. J., 2009, 15, 10167-10172.
83. Ayats, C.; Henseler, A.H.; Pericàs, M.A. A solid-supported organocatalyst for continuous-flow enantioselective aldol reactions. ChemSusChem, 2012, 5, 320-325.
84. Martín-Rapún, R.; Sayalero, S.; Pericàs, M.A. Asymmetric anti-mannich reactions in continuous flow. Green Chem., 2013, 15, 3295-3301.
85. Ayats, C.; Henseler, A.H.; Dibello, E.; Pericas, M.A. Continuous flow enantioselective three-component anti-mannich reactions catalyzed by a polymer-supported threonine derivative. ACS Catal., 2014, 4, 3027-3033.
86. Ötvös, S.B.; Mándity, I.M.; Fülöp, F. Highly efficient 1,4-addition of aldehydes to nitroolefins: organocatalysis in continuous flow by solid-supported peptidic catalysts. ChemSusChem, 2012, 5, 266-269.
87. Arakawa, Y.; Wennemers, H. Enamine catalysis in flow with an immobilized peptidic catalyst. ChemSusChem, 2013, 6, 242-245.
88. Scatena, G.S.; de la Torre, A.F.; Cass, Q.B.; Rivera, D.G.; Paixão, M.W. Multicomponent approach to silica-grafted peptide catalysts: a 3 d continuous-flow organocatalytic system with on-line monitoring of conversion and stereoselectivity. ChemCatChem, 2014, 6, 3208-3214.
89. Ahrendt, K.A.; Borths, C.J.; MacMillan, D.W.C. New strategies for organic catalysis: The first highly enantioselective organocatalytic diels-alder reaction. J. Am. Chem. Soc., 2000, 122, 4243-4244.
90. Chiroli, V.; Benaglia, M.; Cozzi, F.; Puglisi, A.; Annunziata, R.; Celentano, G. Continuous-flow stereoselective organocatalyzed diels-alder reactions in a chiral catalytic “Homemade” hplc column. Org. Lett., 2013, 15, 3590-3593.
91. Porta, R.; Benaglia, M.; Chiroli, V.; Coccia, F.; Puglisi, A. Stereoselective diels alder reactions promoted under continuous-flow conditions by silica-supported chiral organocatalysts. Isr. J. Chem., 2014, 54, 381-394.
92. Chiroli, V.; Benaglia, M.; Puglisi, A.; Porta, R.; Jumde, R.P.; Mandoli, A. A chiral organocatalytic polymer-based monolithic reactor. Green Chem., 2014, 16, 2798-2806.
93. Porta, R.; Benaglia, M.; Puglisi, A.; Mandoli, A.; Gualandi, A.; Cozzi, P.G. A Catalytic Reactor for the Organocatalyzed Enantioselective Continuous Flow Alkylation of Aldehydes. Chem-SusChem, 2014, 7, 3534-3540.
94. Connon, S.J. Chiral phosphoric acids: powerful organocatalysts for asymmetric addition reactions to imines. Angew. Chem. Int. Ed., 2006, 45, 3909-3912.
95. Terada, M. Binaphthol-derived phosphoric acid as a versatile catalyst for enantioselective carbon-carbon bond forming reactions. Chem. Commun., 2008, 35, 4097-4112.
96. Zamfir, A.; Schenker, S.; Freund, M.; Tsogoeva, S.B. Chiral BI-NOL-derived phosphoric acids: privileged Brønsted acid organocatalysts for C-C bond formation reactions. Org. Biomol. Chem., 2010, 8, 5262-5276.
97. Akiyama, T.; Itoh, J.; Yokota, K.; Fuchibe, K. Enantioselective mannich-type reaction catalyzed by a chiral brønsted acid. Angew. Chem. Int. Ed., 2004, 43, 1566-1568.
98. Uraguchi, D.; Terada, M. Chiral Brønsted acid-catalyzed direct Mannich reactions via electrophilic activation. J. Am. Chem. Soc., 2004, 126, 5356-5357.
99. Osorio-Planes, L.; Rodrígues-Escrich, C.; Pericàs, M.A. Enantioselective continuous-flow production of 3-indolylmethanamines mediated by an immobilized phosphoric acid catalyst. Chem. Eur. J., 2014, 20, 2367-2372.
100. Auvil, T.J.; Schafer, A.G.; Mattson, A.E. Design strategies for enhanced hydrogen-bond donor catalysts. Eur. J. Org. Chem., 2014, 13, 2633-2646.
101. Kasaplar, P.; Rodrígues-Escrich, C.; Pericàs, M.A. Continuous flow, highly enantioselective michael additions catalyzed by a ps-supported squaramide. Org. Lett., 2013, 15, 3498-3501.
102. Kardos, G.; Soós, T. Tether-free immobilized bifunctional squaramide organocatalysts for batch and flow reactions. Eur. J. Org. Chem., 2013, 4490-4494.
103. Baxendale, I.R.; Deelay, J.; Griffiths-Jones, C.M.; Ley, S.V.; Saaby, S.; Tranmer, G.F. A flow process for the multi-step synthesis of the alkaloid natural product oxomaritidine: a new paradigm for molecular assembly. Chem. Commun., 2006, 2566-2568.
104. Newton, S.; Carter, C.F.; Pearson, C.M.; de C. Alves, L.; Lange, H.; Thansandote, P.; Ley, S.V. Accelerating spirocyclic polyketide synthesis using flow chemistry. Angew. Chem. Int. Ed., 2014, 53, 4915-4920.
105. Hopkin, M.D.; Baxendale, I.R.; Ley, S.V. An expeditious synthesis of imatinib and analogues utilising flow chemistry methods. Org. Biomol. Chem., 2013, 11, 1822-1839.
106. Dalla Vechia, L.; Reichart, B.; Glasnov, T.; Miranda, L.S.M.; Kappe, C.O.; de Souza, R.O.M.A. A three step continuous flow synthesis of the biaryl unit of the HIV protease inhibitorAtazanavir. Org. Biomol. Chem., 2013, 11, 6806-6813.
107. Chen, M.; Buchwald, S. Continuous-flow synthesis of 1-substituted benzotriazoles from chloronitrobenzenes and amines in a c n bond formation/hydrogenation/diazotization/cyclization sequence. Angew. Chem. Int. Ed., 2013, 52, 4247-4250.
108. Battilocchio, C.; Deadman, B.J.; Nikbin, N.; Kitching, M.O.; Baxendale, I.R.; Ley, S.V. A machine-assisted flow synthesis of sr48692: a probe for the investigation of neurotensin receptor-1. Chem. Eur. J., 2013, 19, 7917-7930.
109. Ingham, R.J.; Battilocchio, C.; Fitzpatrick, D.E.; Sliwinski, E.; Hawkins, J.M.; Ley, S.V. A systems approach towards an intelligent and self-controlling platform for integrated continuous reaction sequences. Angew. Chem. Int. Ed., 2015, 54, 144-148.
110. Ghislieri, D.; Gilmore, K.; Seeberger, P.H. Chemical assembly systems: layered control for divergent, continuous, multistep syntheses of active pharmaceutical ingredients. Angew. Chem. Int. Ed., 2015, 54, 678-682.