Multigramme synthesis and asymmetric dihydroxylation of a 4-fluorobut-2E-enoate

Esters of crotonic acid were brominated on a multigramme scale using a free radical procedure. A phase transfer catalysed fluorination transformed these species to the 4-fluorobut-2E-enoates reproducibly and at scale (48–53%, ca. 300 mmol). Asymmetric dihydroxylation reactions were then used to transform the butenoate, ultimately into all four diastereoisomers of a versatile fluorinated C(4) building block at high enantiomeric-enrichment. The (DHQ)(2)AQN and (DHQD)(2)AQN ligands described by Sharpless were the most effective. The development and optimisation of a new and facile method for the determination of ee is also described; (19)F{(1)H} spectra recorded in d-chloroform/diisopropyl tartrate showed distinct baseline separated signals for different enantiomers.