ABSTRACT
A spirocyclic, sp3-atom rich oxetane-containing scaffold was synthesised in just two steps via a gold catalysed propargylic alcohol rearrangement. The key gold cyclisation can be undertaken on a 40â¯g scale allowing the preparation of 419 lead-like compounds based on the scaffold for the European Lead Factory.
Subject(s)
Drug Design , Ethers, Cyclic/chemistry , Piperidines/chemistry , Small Molecule Libraries/chemistry , Catalysis , Cyclization , Gold/chemistry , Small Molecule Libraries/chemical synthesisABSTRACT
A new class of fluorinated lactones was prepared by the intramolecular fluorocyclizations of unsaturated carboxylic acids by using the stable fluoroiodane reagent in combination with AgBF4. This unique reaction incorporates a cyclization, an aryl migration, and a fluorination all in one step. The fluoroiodane reagent, prepared easily from fluoride, can also be used without a metal catalyst to give moderate yields within just 1â hour, thus demonstrating that it is a suitable reagent for developing new (18)F-labelled radiotracers for PET imaging.
ABSTRACT
The air and moisture stable fluoroiodane 8, readily prepared on a 6 g scale by nucleophilic fluorination of the hydroxyiodane 7 with TREAT-HF, has been used as an electrophilic fluorinating reagent for the first time to monofluorinate 1,3-ketoesters and difluorinate 1,3-diketones in good isolated yields.
