Highly efficient continuous flow reactions using singlet oxygen as a "green" reagent.

Described is a new method for the efficient in situ production of singlet oxygen in a simple continuous flow photochemical reactor. The extremely large interfacial area generated by running the biphasic mixture in a narrow channel at a high flow rate ensures high throughput as well as fast and efficient oxidation of various alkenes, 1,3-dienes, and thioethers on a preparative scale.

[1]  Andreas Kirschning,et al.  Ten key issues in modern flow chemistry. , 2011, Chemical communications.

[2]  K. Jähnisch,et al.  Photochemical Generation and [4+2]‐Cycloaddition of Singlet Oxygen in a Falling‐Film Micro Reactor , 2005 .

[3]  N. Hoffmann,et al.  Photochemical reactions as key steps in organic synthesis. , 2008, Chemical reviews.

[4]  J. Armitage,et al.  SAFETY CONSIDERATIONS IN INDUSTRIAL USE OF ORGANIC PEROXIDES , 1964 .

[5]  Robert C. R. Wootton,et al.  A Microfabricated Nanoreactor for Safe, Continuous Generation and Use of Singlet Oxygen , 2002 .

[6]  H. Vial,et al.  Synthesis and antimalarial activity of trioxaquine derivatives. , 2004, Chemistry.

[7]  P. Mayo,et al.  Photochemical rearrangement of diene endoperoxides , 1970 .

[8]  Mark Pickworth,et al.  A practical flow reactor for continuous organic photochemistry. , 2005, The Journal of organic chemistry.

[9]  K. Ulbrich,et al.  HPMA copolymer conjugates of paclitaxel and docetaxel with pH-controlled drug release. , 2010, Molecular pharmaceutics.

[10]  P. Seeberger,et al.  Optimization of Glycosylation Reactions in a Microreactor , 2007 .

[11]  B. Lohray,et al.  Novel 4-N-substituted aryl pent-2-ene-1,4-dione derivatives of piperazinyloxazolidinones as antibacterials. , 2006, Bioorganic & medicinal chemistry letters.

[12]  K. Pfoertner Photochemistry in industrial synthesis , 1990 .

[13]  G. Ohloff Singlet oxygen: a reagent in organic synthesis , 1975 .

[14]  T. Karayiannis,et al.  The effect of tube diameter on vertical two-phase flow regimes in small tubes , 2006 .

[15]  R. Schmidt,et al.  Radiationless deactivation of singlet oxygen (1.DELTA.g) by solvent molecules , 1987 .

[16]  G. Schenck Probleme präparativer Photochemie , 1952 .

[17]  F. Toste,et al.  Enantioselective Synthesis of γ-Hydroxyenones by Chiral Base-Catalyzed Kornblum DeLaMare Rearrangement , 2006 .

[18]  P. Seeberger,et al.  Continuous flow thermolysis of azidoacrylates for the synthesis of heterocycles and pharmaceutical intermediates. , 2011, Chemical communications.

[19]  Takehiko Kitamori,et al.  A Microfluidic Device for Conducting Gas-Liquid-Solid Hydrogenation Reactions , 2004, Science.

[20]  V. Lucchini,et al.  Photooxygenation of olefins in the presence of titanium(IV) catalyst. A convienient "one-pot" synthesis of epoxy alcohols. , 1989 .

[21]  Hong Cao,et al.  HIV-1 protease inhibitors from inverse design in the substrate envelope exhibit subnanomolar binding to drug-resistant variants. , 2008, Journal of the American Chemical Society.

[22]  Liwei Pan,et al.  Flow Pattern, Pressure Drop, and Mass Transfer in a Gas−Liquid Concurrent Two-Phase Flow Microchannel Reactor , 2009 .

[23]  Reinhard Schmidt,et al.  Physical mechanisms of generation and deactivation of singlet oxygen. , 2003, Chemical reviews.

[24]  A. Griesbeck,et al.  Interactions of singlet oxygen with 2,5-dimethyl-2,4-hexadiene in polar ano non-polar solvents evidence for a vinylog ene-reaction , 1984 .

[25]  P. Knochel,et al.  Novel chiral diphosphine ligands with a pinene core obtained via an allylphosphinite–allylphosphine oxide rearrangement , 2004 .

[26]  Wolfgang Ehrfeld,et al.  Direct fluorination of toluene using elemental fluorine in gas/liquid microreactors , 2000 .

[27]  L. Luo,et al.  An experimental investigation of gas–liquid two-phase flow in single microchannel contactors , 2008 .

[28]  K. Paulvannan An atom-economical approach to conformationally constrained tricyclic nitrogen heterocycles via sequential and tandem Ugi/intramolecular Diels-Alder reaction of pyrrole. , 2004, The Journal of organic chemistry.

[29]  Xue Han,et al.  Cleaner continuous photo-oxidation using singlet oxygen in supercritical carbon dioxide. , 2009, Angewandte Chemie.

[30]  Daniel A. Crowl,et al.  Application of the flammability diagram for evaluation of fire and explosion hazards of flammable vapors , 1998 .

[31]  D. Sawicka,et al.  An intramolecular oxo Diels-Alder approach to 1-oxo-1,2,3,3a, 4,7a-hexahydro-pyrano[3,4-c]pyrrole-4-carboxylic acid ethyl esters , 2003 .

[32]  G. Kreisel,et al.  Photosensitized oxidation of citronellol in microreactors , 2007 .

[33]  Peter H Seeberger,et al.  Oligosaccharide synthesis in microreactors. , 2007, Organic letters.

[34]  Dennis K. Taylor,et al.  Synthesis and chemistry of 2,3-dioxabicyclo[2.2.2]octane-5,6-diols. , 2009, The Journal of organic chemistry.

[35]  Dwight W. Chasar,et al.  STANDING COMMITTEESS: DIVISIONAL ACTIVITIES , 2005 .

[36]  Michael Oelgemöller,et al.  Micro-photochemistry: photochemistry in microstructured reactors. The new photochemistry of the future? , 2008, Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology.

[37]  O. Neumüller,et al.  Zur photosensibilisierten Autoxydation der Steroide: Δ5‐Steroid‐7α‐hydroperoxyde und ‐7‐ketone durch Allylumlagerung von Δ6‐Steroid‐5α‐hydroperoxyden , 1958 .