Alexander Stadler

Solid- and solution-phase synthesis of bioactive dihydropyrimidines

With the emergence of high-throughput screening in the pharmaceutical industry over a decade ago, synthetic chemists were faced with the challenge of preparing large collections of molecules to satisfy the demand for new screening compounds. The unique exploratory power of multicomponent reactions such as the Biginelli three-component reaction was soon recognized to be extremely valuable to produce compound libraries in a time- and cost-effective manner. The present review summarizes synthetic advances from our laboratories for the construction of Biginelli libraries via solution-and solid-phase strategies that are amenable to a high-throughput or combinatorial format.

The Scale-Up of Microwave-Assisted Organic Synthesis

Single-mode microwave reactors have been very successful in the past few years in the field of method development and optimization. Future trends clearly indicate the use of microwave technology for the development of completely new reaction routes for organic synthesis, with increasing demand for large-scale microwave production of chemical substances (>100 g per run). For microwave-assisted synthesis to become a fully accepted industrial technology in the future, there is a need to develop techniques that can ultimately routinely provide products on a multikilogram scale. Thus, the further development of large reactors, at least in the pilot plant scale to enable multikilogram production of lead compounds, is required. Herein are discussed several already known scale-up processes in microwave-assisted organic chemistry in a ≥50 mL batch scale and experiments performed with both continuous flow and stop-flow techniques. Furthermore, the available instrumentation for scale-up at laboratory scale and beyond is presented.

High-speed microwave-promoted Mitsunobu inversions. Application toward the deracemization of sulcatol

An enantioconvergent synthesis of the aggregation pheromones (R)- and (S)-sulcatol (6-methyl-5-hepten-2-ol) is described. Key steps in the deracemization strategy are sequential combinations of enzymatic resolutions and Mitsunobu inversions. Racemization-free Mitsunobu transformations have been carried out within 5 min by microwave irradiation, providing the desired sulcatyl acetates with clean inversion of chirality.

Neat carbomethoxypivaloylketene—preparation and chemical reactivity

Abstract Neat carbomethoxypivaloylketene, the first fairly persistent α-oxoketene stabilized both electronically as well as sterically, is generated by flash vacuum pyrolysis of the corresponding furan-2,3-dione. It adds primary amines to afford pivaloyl-malonic acid amides and undergoes hetero-Diels–Alder reactions to furnish usual and unusual [4+2] adducts. Some stereo- and regiochemical features are verified with aid of 2D NMR experiments and a X-ray structure analysis.

Microwave‐Assisted Syntheses in Recyclable Ionic Liquids: Photoresists Based on Renewable Resources

The copoly(2-oxazoline) pNonOx80-stat-pDc=Ox20 can be synthesized from the cationic ring-opening copolymerization of 2-nonyl-2-oxazoline NonOx and 2-dec-9′-enyl-2-oxazoline Dc=Ox in the ionic liquid n-hexyl methylimidazolium tetrafluoroborate under microwave irradiation in 250 g/batch quantities. The polymer precipitates upon cooling, enabling easy recovery of the polymer and the ionic liquid. Both monomers can be obtained from fatty acids from renewable resources. pNonOx80-stat-pDc=Ox20 can be used as polymer in a photoresist (resolution of 1 μm) based on UV-induced thiol–ene reactions.

ADVENTURES IN MICROWAVE-ASSISTED ORGANIC SYNTHESIS: CONTRIBUTIONS FROM THE KAPPE LABORATORY 2000-2005

This review highlights work in the field of microwave-assisted organic synthesis (MAOS) originating from the Kappe research laboratories in Graz, Austria. The focus of the article is on synthetic applications in the area of heterocyclic chemistry, multicomponent reactions, transition metal- catalyzed processes, solid-phase synthesis and combinatorial chemistry.