Advanced Concepts for Catalysis in Synthesis and Flow Chemistry

Thomas Wirth

School of Chemistry, Cardiff University, Cardiff CF10 3AT, UK

wirth@cf.ac.uk Abstract: The development of catalytic reactions based on stoichiometric reactions using selenium- and iodine-based reagents will be discussed. Novel chiral reagents and catalysts allow the easy synthesis of versatile scaffolds as synthetic building blocks as well as applications towards natural product synthesis. The contact between immiscible liquids in a microfluidic system creating segmented flow offers great potential in the study of biphasic reactions in organic chemistry with significant advantages with respect to conventional flask techniques. This can dramatically increase the reaction rate, especially when microwave irradiation, sonication or phase transfer catalysis are combined with segmentation. Metal-catalyzed sequences can also be performed advantageously in biphasic systems. Chemistry with hazardous chemicals, the synthesis of radiopharmaceuticals and the development of a microreactor for electrochemistry will be discussed. Selected recent publications: • Fast Synthesis of Benzofluorenes by Selenium-Mediated Carbocyclizations

S. A. Shahzad, T. Wirth, Angew. Chem. Int. Ed. 2009, 48, 2588 – 2591. • A New Versatile and Highly Reactive Polyfluorinated Hypervalent Iodine(III) Compound

S. Schäfer, T. Wirth, Angew. Chem. Int. Ed. 2010, 49, 2786 – 2789. • A practical microreactor for electrochemistry in flow

K. Watts, W. Gattrell, T. Wirth, Beilstein J. Org. Chem. 2011, 7, 1108 – 1114. • Ritter Reactions in Flow

L. Audiger, S. C. Elmore, R. I. Robinson, T. Wirth, ChemSusChem 2012, 5, 257-260. • Highly Stereoselective Metal-free Oxyaminations using Chiral Hypervalent Iodine Reagents

U. Farid, T. Wirth, Angew. Chem. Int. Ed. 2012, 51, 3462 – 3467. • Stereoselective Rearrangements with Chiral Hypervalent Iodine Reagents

U. Farid, F. Malmedy, R. Claveau, L. Albers, T. Wirth, Angew. Chem. Int. Ed. 2013, 52, 7018 – 7022. • Efficient Terpene Synthase Catalysis by Extraction in Flow

O. Cascón, G. Richter, R. K. Allemann, T. Wirth, ChemPlusChem 2013, 78, 1334 – 1337 • Microreactors in Organic Chemistry and Catalysis 2nd Edition (book)

Ed.: T. Wirth, Wiley-VCH, 2013. • Flexible Functionalizations of Carbonyl Compounds through Umpolung using Hypervalent Iodine

Reagents P. Mizar, T. Wirth, Angew. Chem. 2014, 126, 6103 – 6107; Angew. Chem. Int. Ed. 2014, 53, 5993 – 5997.

• Stereoselective Diamination with Novel Chiral Hypervalent Iodine Catalysts P. Mizar, A. Laverny, M. El-Sherbini, U. Farid, M. Brown, F. Malmedy, T. Wirth, Chem. Eur. J. 2014, 20, 9910 – 9913.

Thomas Wirth is professor of organic chemistry at Cardiff University. After studying chemistry in Bonn/Germany and at the Technical University of Berlin/Germany, he obtained his PhD in 1992 with Professor S. Blechert. After a postdoctoral stay with Professor K. Fuji at Kyoto University a JSPS fellow, he started his independent research at the University of Basel/Switzerland. In the group of Professor B. Giese he obtained his habilitation on stereoselective oxidation reactions supported by various scholarships before taking up his current position at Cardiff University in 2000. He was invited as a visiting professor to a number of places including the University of Toronto/Canada (1999), Chuo University in Tokyo (2000), Osaka University (2004), Osaka Prefecture University (2008) and with a JSPS fellowship to Kyoto University (2012). He was awarded the Werner-Prize from the New Swiss Chemical Society (2000) and the Furusato award from JSPS London (2013). His main interests of research concern stereoselective electrophilic reactions, oxidative transformations with hypervalent iodine reagents including mechanistic investigations and organic synthesis performed in microreactors.

.About 30 % of the world’s iodine …… production comes from the Chiba area in Japan, shown in the background of thepicture (Map data !2012 ZENRIN Imagery !2012 TerraMetrics). Enantiomerically purehypervalent iodine compounds are the key for metal-free, highly stereoselectiveoxyaminations of alkenes. In their Communication on page 3462 ff., T. Wirth and U.Farid report the use of the reaction for the facile synthesis of 2-arylprolinols.

Second, Completely Revised and Enlarged Edition

Edited by Thomas Wirth

Microreactors in Organic Chemistry and Catalysis