A Continuous Flow Process for LSN647712 via Double Organometallic Additions to Dimethylcarbamyl Chloride.

The ketone intermediate LSN647712 is a key synthetic intermediate for the drug substance lasmiditan manufacturing process. A three-step connected continuous flow process utilizing a Turbo Grignard reagent, N-methylpiperidin-4-ylmagnesium chloride, and lithiated 2,6-dibromopyridine sequentially added to double electrophile (O═C(++) synthon dimethylcarbamyl chloride (DMCC) was developed to deliver the ketone intermediate in a high chemical yield (>85%). This highly productive (>100 g/h lab system) and intensified process (τ ∼ 3 min) yields the product in high purity upon batch reactive crystallization to form a corresponding hydrobromide salt. In addition to the connected plug flow reactor system, the Grignard reagent, N-methylpiperidin-4-ylmagnesium chloride, was also prepared continuously in CSTR as a more soluble LiCl adduct in THF (Turbo Grignard).

Axial shielding of Pd(II) complexes enables perfect stereoretention in Suzuki-Miyaura cross-coupling of Csp3 boronic acids.

Stereocontrolled Csp3 cross-coupling can fundamentally change the types of chemical structures that can be mined for molecular functions. Although considerable progress in achieving the targeted chemical reactivity has been made, controlling stereochemistry in Csp3 cross-coupling remains challenging. Here we report that ligand-based axial shielding of Pd(II) complexes enables Suzuki-Miyaura cross-coupling of unactivated Csp3 boronic acids with perfect stereoretention. This approach leverages key differences in spatial orientation between competing pathways for stereoretentive and stereoinvertive transmetalation of Csp3 boronic acids to Pd(II). We show that axial shielding enables perfectly stereoretentive cross-coupling with a range of unactivated secondary Csp3 boronic acids, as well as the stereocontrolled synthesis of xylarinic acid B and all of its Csp3 stereoisomers. We expect these ligand design principles will broadly enable the continued search for practical and effective methods for stereospecific Csp3 cross-coupling.

Unified Approach to Substituted Allenoates via Pd-Catalyzed ß-Hydride Elimination of (E)-Enol Triflates.

A robust synthesis of allenoates via a Pd-catalyzed ß-hydride elimination of (E)-enol triflates is presented. Salient features of this method include low catalyst loadings, mild reaction conditions, and the ability to access all four patterns of substituted allenoates from a single substrate class.

Ultrasonic sensor based defect detection and characterisation of ceramics.

Ceramic tiles, used in body armour systems, are currently inspected visually offline using an X-ray technique that is both time consuming and very expensive. The aim of this research is to develop a methodology to detect, locate and classify various manufacturing defects in Reaction Sintered Silicon Carbide (RSSC) ceramic tiles, using an ultrasonic sensing technique. Defects such as free silicon, un-sintered silicon carbide material and conventional porosity are often difficult to detect using conventional X-radiography. An alternative inspection system was developed to detect defects in ceramic components using an Artificial Neural Network (ANN) based signal processing technique. The inspection methodology proposed focuses on pre-processing of signals, de-noising, wavelet decomposition, feature extraction and post-processing of the signals for classification purposes. This research contributes to developing an on-line inspection system that would be far more cost effective than present methods and, moreover, assist manufacturers in checking the location of high density areas, defects and enable real time quality control, including the implementation of accept/reject criteria.

Pd-catalyzed asymmetric ß-hydride elimination en route to chiral allenes.

We wish to report our preliminary results on the discovery and development of a catalytic, asymmetric ß-hydride elimination from vinyl Pd(II)-complexes derived from enol triflates to access chiral allenes. To achieve this, we developed a class of chiral phosphite ligands that demonstrate high enantioselectivity, allow access of either allene enantiomer, and are readily synthesized. The methodology is demonstrated on over 20 substrates, and application to the formal asymmetric total synthesis of the natural product, (+)-epibatidine, is also provided.

Effect of kafirin protein coating on sensory quality and shelf-life of 'Packham's Triumph' pears during ripening.

BACKGROUND: Pears are exported in large quantities from South Africa, resulting in large revenues. Minimisation of quality losses once the fruit has reached the export destination is as important as following strict export and distribution protocols. Kafirin can form edible films. In this study an edible coating made from 20 g kg(-1) kafirin coating solution was applied as a postharvest treatment to retard quality deterioration of 'Packham's Triumph' pears during storage at the typical ripening temperature (20 °C). Changes in physicochemical and sensory quality were monitored over a period of 24 days. RESULTS: The kafirin coating was unable to retard the onset of ripening but decreased the respiration rate and retarded the progression of senescence. However, moisture loss was exacerbated in the kafirin-coated fruit during ripening at 20 °C, especially towards the end of the shelf-life. CONCLUSION: The kafirin coating extended the eat-ripe quality of the pears by 1-2 weeks. However, the appearance of the fruit was unacceptable after 14 days of storage in terms of wrinkled skin. Further work is needed to improve the water barrier properties of the kafirin coating by incorporating a wax or triglyceride into the coating formulation or more simply by applying a kafirin coating to waxed fruit.