The hydrofluorination of enolizable ynones with AgF in t-BuOH/DMF is reported. The formation of furans as side products can be suppressed using 2,2'-biphenol. The corresponding β-fluoroenones were obtained with good Z-selectivity. A variety of functional groups are tolerated. β-Fluoroenones are vinylogous acid fluorides whose hydrolysis to vinylogous acids can be avoided under the reported reaction conditions. The asymmetric 1,2-reduction of β-fluoroenones to 3-fluoroallylic alcohols is possible with pinacolborane and a Ni(0) catalyst prepared from a pyrimidyloxazoline ligand.

Bicyclic peptides have great therapeutic potential since they can bridge the gap between small molecules and antibodies by combining a low molecular weight of about 2 kDa with an antibody-like binding specificity. Here we apply a recently developed in silico rational design strategy to produce a bicyclic peptide to target the C-terminal region (residues 31–42) of the 42-residue form of the amyloid β peptide (Aβ42), a protein fragment whose aggregation into amyloid plaques is linked with Alzheimer’s disease. We show that this bicyclic peptide is able to remodel the aggregation process of Aβ42 in vitro and to reduce its associated toxicity in vivo in a C. elegans worm model expressing Aβ42. These results provide an initial example of a computational approach to design bicyclic peptides to target specific epitopes on disordered proteins.

A rhodium catalyzed allylic cyanation of 3‐fluoroallylic trifluoroacetates with TMSCN and a bulky phosphite ligand gives 3‐fluoroallylic nitriles with a good substrate scope and high Z/E‐selectivity. For dialkylated substrates the fluorine substituent controls the regioselectivity in favor of the distal product. For the stereoselectivity of the allylic cyanation selected scalemic substrates showed inversion of the stereocenter and some or no stereoerosion.