Palladium catalysts enantioselective fluorination

Catalysts (25) are the Lewis acid-Lewis base bifunctional catalysts in which Lewis acid-Al(III) moiety activates acyl iminium ion and the Lewis base (oxygen of phosphine oxide) does TMSCN, simultaneously (Scheme 5.7). Halogen atoms at the 6-position enhanced both yields and enantioselectivity in Reissert-type cyanation of the imino part of 26. However, the order for the activation is not parallel to the electronegativity of the halogen atoms and, moreover, the strong electron-withdrawing trifluoromethyl group provided unexpectedly the worst result for the activation [13]. It is not simple to explain this phenomenon only in terms of the increased Lewis acidity of the metal center. Trifluoromethylated BINOL-zirconium catalysts (28) for asymmetric hetero Diels-Alder reaction (Scheme 5.8) [14], trifluoromethylated arylphosphine-palladium catalyst (32) for asymmetric hydrosilylation (Scheme 5.9) [15], and fluorinated BINOL-zinc catalyst (35) for asymmetric phenylation (Scheme 5.10) [16] are known. 

Likewise, 2-cyanophosphonates undergo enantioselective fluorination reactions to products with almost the same enantiomeric excesses. Due to the linear nitrile group, these reactions are believed to proceed without efficient chelation and hence require the presence of additional base. To this end, pyridine derivatives were found to be best. Sodeoka described a combination of lutidine and her dimeric hydroxyl-bridged palladium dimer as catalyst precursor, [31] while Kim relied on a sterically more congested pyridine in combination with a XylBINAP catalyst [29, 32]. 

The catalytic enantioselective fluorination of oxindoles by using a BINAP-palladium catalyst also proceeded highly efficiently without exclusion of air and moisture to give the corresponding fluorinated oxindoles in good yields with high-to-excellent enantioselectivities (up to 96%... 

In these cases, NFSI was preferred to Selectfluor and the reactions were performed either in alcohol or in ionic liquids in which the palladium complexes can be immobilized and reused with excellent reproducibility even after 10 consecutive cycles. For example, the enantioselective electrophilic fluorination of 2-methyl-3-oxo-3-phenylpro-pionic acid tert-butyl ester in [hmim] [BF4] gives the corresponding fluorinated product in 93% yield with 92% ee, and still in 67% yield with 91% ee after 10 cycles. The fluorination of various cyclic and acyclic (3-keto esters was carried out with NFSI in ethanol in the presence of 2.5 mol% of catalyst, leading to excellent ee-values up to 94%. The reaction is not sensitive to water, can be run on a 1-g scale, and proceeds via a palladium enolate complex as for the titanium-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyl-dioxolane (TADDOL) catalyst. The reaction was extended to tert-butoxycarbonyl lactones and lactams. Reactions with lactones proceeded smoothly in an alcoholic solvent with 2.5 mol% of catalyst and NFSI, while the less acidic lactam substrates required concurrent use of the Pd complex and 2,6-lutidine as a co-catalyst. Under the reaction conditions, the fluorinated lactones and lactams were obtained in good yields with excellent enantioselectivities (up to 99%... 

---