Screening of chiral catalysts for enantioselective electrophilic fluorination of β-ketoesters

Asymmetric Fluorination, Trifluoromethylation, and Perfluoroalkylation Reactions

“…In addition, the use of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), as an additive, allowed 10−15% enantiomeric excess to be gained in all the reactions (Table ) . Other combinations of chiral ligand (sparteine, cinchona alkaloids, PyBOX, Trost's ligand, BINOL) and metal (Zn, Mg, Al, Sc, La) as well as various N−F reagents were screened, leading to enantioenriched α-fluoro-β-keto esters in high yields and moderate enantioselectivities (up to 67% ee) 11 Enantioselective Fluorination Catalyzed by BOX−Copper Complexes producttime, hyield, %ee, % 99 48 72 52 108 0.5 96 85 109 3 92 63 111 96 56 43 114 0.5 94 35 115 0.5 92 38 116 2 88 40 …”

Modern Approaches for Asymmetric Construction of Carbon–Fluorine Quaternary Stereogenic Centers: Synthetic Challenges and Pharmaceutical Needs

“…In 2004, the Cahard group reported that ( R , R )-BOX-Ph complexes of not only Cu­(OTf) 2 (Scheme a) but also various other metal salts such as Mg­(ClO 4 ) 2 , Zn­(OTf) 2 , Sc­(OTf) 3 , and La­(OTf) 3 can catalyze the fluorination reaction of β-keto esters. , Although only low enantioselectivity (up to 17% ee) was observed for the reaction using Mg and lanthanoid complexes, reasonably high asymmetric induction was observed when the ( R , R )-BOX-Ph-Zn­(OTf) 2 complex was used as a catalyst (up to 74% ee). They also tested a heterobimetallic complex, Al–Li–BINOL, and obtained moderate asymmetric induction (up to 67% ee) when NFPY-BF 4 was used as fluorinating reagent . In 2005, Jørgesen reported that ( R , R )-DBFOX-Zn­(ClO 4 ) 2 catalyzed asymmetric fluorination of β-keto phosphonates 210 (Scheme a) .…”

Bifunctional organo/metal cooperative catalysis with cinchona alkaloid scaffolds

“…Cahard and Ma gained low enantioselectivities (22% ee) in the fluorination of b-ketoesters using a combination of cinchona-alkaloid derivatives and Cu II or Zn II ions. 82 Shibata and his research group synthesized 3 0 -fluorothalidomide by enantioselective fluorination with the help of a dihydroquinine(DHQ)/Cu II /Li I combination. 83 Both reagents were used in super-stoichiometric amounts but a new kind of enantioselectivity dependent on the type of Lewis acid was discovered.…”