The realm of combinatorial chemistry is strongly based on the concept of parallel chemistry and its ease of automation. Although this batch-type approach in general may be considered a success story, some limitations remain rarely addressable by conventional approaches. Particularly, scaling-up problems such as the re-synthesis of multigram amounts of active compounds as well as the synthesis of building blocks and scaffolds in large amounts may prove to be problematic. Our expertise in continuous chemistry prompted us to develop a microreaction system for sequential organic synthesis that should overcome these limitations. In the present contribution we describe this system as well as its application to the first library approach towards fluoro-quinolone antibiotics such as Ciprofloxacin solely using microreaction technology. A known one-pot batch procedure for the synthesis of this compound class was split in its individual reaction steps, which were successfully adapted to a continuous conduct. After some optimisation studies the overall sequence was suitable for chemical diversification. Particularly it was shown, that the first step of the synthesis -the acylation reaction of a b-dimethylamino acrylate with trifluoro-benzoic acid chloride -was accessible to synthesis of high quantities without any difficulties to yield a primary building block suitable for subsequent library synthesis. In a first diversification step, the Michael addition of a set of primary amines was followed by nucleophilic ring closure providing the difluoroquinolone system, which was subjected to a second diversification step by means of a nucleophilic aromatic substitution reaction. Thus, a number of Ciprofloxacin analogues could be synthesised in good overall yield and purity. Isolated yields ranged from 71 to 85% in the first diversification step and from 59 to 99% in the second step.

The title compounds are enantioselectively synthesized in just two preparative steps, making use of the Ugi-four-component reaction with an amino acid as chiral component, followed by a gold-catalyzed hydroamination.

Me4N+SOF3 -, the first example of a SOF3 - salt, has been prepared from Me4NF and SOF2. The colorless, microcrystalline solid was characterized by its Raman and infrared spectra, and in acetonitrile solution by 19F NMR. The structure of the SOF3 - anion is predicted by ab initio calculations to possess a pseudo trigonal bipyramidal structure with two remarkably long sulfur−fluorine bonds in the axial position. One fluorine, the oxygen atom, and a sterically active lone pair of electrons occupy the equatorial plane.

Butanone side chains at arenes and hetarenes, efficiently introduced by a Heck-type reaction, are transformed to annulated thieno[3,2-b]thiophenes in a domino redox process under Willgerodt-Kindler conditions. A nucleophilic aromatic substitution with an intermediary thioenolate is a reasonable key step of this process.

[Me(4) N](+) [SO(2) F(3) ](-) , the first example of a [SO(2) F(3) ](-) salt, has been prepared from Me(4) NF and SO(2) F(2) . The colorless, microcrystalline solid was characterized by its infrared and Raman spectra. The trigonal bipyramidal structure of C(2v) symmetry of the [SO(2) F(3) ](-) anion is predicted by ab initio calculations. Two oxygen atoms with d(SO)=143.2 pm and one fluorine atom with d(SF)=157.9 pm occupy the equatorial plane. The two fluorine atoms in the axial position with d(SF)=168.5 pm are repulsed by the two oxygen atoms forming a bent axis with ∡(F(ax) SF(ax) )=165.2°.