Organic Chemistry Portal
Organic Chemistry Highlights

Monday, September 28, 2015
Douglass F. Taber
University of Delaware

Flow Chemistry

Arturo Macchi of the University of Ottawa and Dominique M. Roberge of Lonza summarized (Org. Process Res. Dev. 2014, 18, 1286. DOI: 10.1021/op5001918) a "toolbox approach" for the evolution from batch to continuous chemical synthesis. Michael D. Organ of York University developed (Org. Process Res. Dev. 2014, 18, 1315. DOI: 10.1021/op5002512) a flow reactor with inline analytics, and Timothy D. White of Eli Lilly described (Org. Process Res. Dev. 2014, 18, 1482. DOI: 10.1021/op500239f) the continuous production of solid products under flow conditions.

Electrochemical reduction and oxidation are particularly easy under flow conditions. Steven V. Ley of the University of Cambridge oxidized (Org. Lett. 2014, 16, 4618. DOI: 10.1021/ol502201d) 1 under flow conditions, then condensed the product with tryptamine 2 to prepare the indole alkaloid Nazlinine (3). Thomas Wirth of Cardiff University electrolyzed (Org. Process Res. Dev. 2014, 18, 1377. DOI: 10.1021/op500155f) the carbonate 4 in a non-divided cell to return the deprotected phenol 5.

Timothy Noël of the Eindhoven University of Technology gathered (Chem. Eur. J. 2014, 20, 10562. DOI: 10.1002/chem.201400283) an overview of photochemical transformations under flow conditions. Kevin I. Booker-Milburn of the University of Bristol observed (Chem. Eur. J. 2014, 20, 15226. DOI: 10.1002/chem.201404347) superior yields for the coupling of 6 with 7 to form 8 under flow compared to batch conditions. Koichi Fukase of Osaka University and Ilhyong Ryu of Osaka Prefecture University converted (Chem. Eur. J. 2014, 20, 12750. DOI: 10.1002/chem.201402303) 9 selectively to 10 under flow conditions. Alexei A. Lapkin, also of the University of Cambridge, optimized (Org. Process Res. Dev. 2014, 18, 1443. DOI: 10.1021/op500181z) the singlet oxygen conversion of 11 to 12. Shawn K. Collins of the Université de Montréal cyclized (Org. Process Res. Dev. 2014, 18, 1571. DOI: 10.1021/op5002148) 13 to 14.

There have been several advances in the use of enzymes under flow conditions. Rodrigo O. M. A. de Souza of the Federal University of Rio de Janeiro found (Org. Process Res. Dev. 2014, 18, 1372. DOI: 10.1021/op500136c) that lipase in a microemulsion-based organogel efficiently converted coupled 15 with 16 to make 17. Timothy F. Jamison of MIT developed (Org. Lett. 2014, 16, 6092. DOI: 10.1021/ol502712v) a catch and release protocol for the reductive amination of 18 to 19.

Flow conditions are particularly suited for the transient generation of reactive intermediates. Dionicio Siegel, now at the University of California, San Diego used (Org. Lett. 2014, 16, 3628. DOI: 10.1021/ol501497y) in situ generated phthaloyl peroxide 22 to oxidize 21 to 23. Katja Buehler of TU Dortmund University employed (Org. Process Res. Dev. 2014, 18, 1516. DOI: 10.1021/op5002116) a combination of enzymes to effect the oxidation of 24 to 25. Thomas L. LaPorte of Bristol-Myers Squibb depended (Org. Process Res. Dev. 2014, 18, 1492. DOI: 10.1021/op500176z) on flow conditions to control the exothermic oxidation of 26 to 27. Frederic G. Buono of Boehringer Ingelheim found (Org. Process Res. Dev. 2014, 18, 1527. DOI: 10.1021/op500263m) flow conditions useful for optimizing the preparation of 30 by the addition of 29 to 28. Toby Broom of GlaxoSmithKline generated (Org. Process Res. Dev. 2014, 18, 1354. DOI: 10.1021/op400090a) the trifluoroborate 32, ready for Suzuki-Miyaura coupling, under flow conditions.

The value of flow was underlined by the preparation of 34 from 33 developed (Org. Process Res. Dev. 2014, 18, 1360. DOI: 10.1021/op5001435) by C. Oliver Kappe of the University of Graz. The explosive trinitro intermediate could be generated and then reduced without any need for isolation.

D. F. Taber, Org. Chem. Highlights 2015, September 28.