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

Abstract

SummaryEsters 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 C4 building block at high enantiomeric-enrichment. The (DHQ)2AQN and (DHQD)2AQN 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; 19F{1H} spectra recorded in d-chloroform/diisopropyl tartrate showed distinct baseline separated signals for different enantiomers.

Application of chiral ligands: carbohydrates, nucleoside-lanthanides and other Lewis acid complexes to control regio- and stereoselectivity of the dipolar cycloaddition reactions of nitrile oxides and esters

“…IR (lm, cm Ethyl tridec-(2E)-2-enoate (3e). 39 NaH 60% (1.5 mmol) of THF was added dropwise with stirring at 0 C over 10 min to the solution of diisopropyl (ethoxycarbonylmethyl)phosphonate (1 mmol) in anhydrous Et 2 O and the solution was stirred at 0 C and then at rt for 60 min. The solution was cooled to À15 C and an aldehyde 1 (1 mmol) solution in anhydrous THF was added dropwise with stirring over 20-30 min and then the solution was stirred at rt for 24 h under anhydrous argon.…”