- Vicinal bromofluoroalkanes: Their regioselective formation and their conversion to fluoroolefins
-
The reaction of alkenes with N-bromosuccinimide and triethylamine tris(hydrofluoride) produces vic-bromofluoroalkanes (1) with high yields. As long as the addition to the double bond is sterically unhindered, bromine and fluorine get attached with very high regioselectivity, the latter halogen occupying the more substituted, carbocation stabilizing position. 2-Fluoro-1-alkenes give 1-bromo-2,2-di-fluoroalkanes (4). The heavier halogen may be removed by base promoted dehydro-fluorination, to afford fluoroolefins (2), or by reduction with tributyltin hydride, leading to mono- or difluoroalkanes (e.g., 5).
- Suga, Hiroaki,Hamatani, Takeshi,Guggisberg, Yves,Schlosser, Manfred
-
-
Read Online
- β,β-Difluoro analogs of α-oxo-β-phenylpropionic acid and phenylalanine
-
A simple three-step procedure converted the readily accessible (2-bromo-1,1-difluoroethyl)arenes (2) into α-aryl-α,α- difluoroacetaldehydes (1). Subsequent hydrocyanation, hydrolysis, oxidation and again hydrolysis afforded β-aryl-β,β-difluoro-α- oxopropionic acids (3). Reductive amination transformed the oxoacids 3 into a separable mixture of α-hydroxyacids 11 and racemic β,β-difluoro- β-phenylalanine derivatives (4). Enantiomerically pure β,β- difluorophenylalanine (L-4a) was obtained when α,α-difluoro-α- phenylacet-aldehyde (1a) was condensed with homochiral 1-phenylethylamine, hydrogen cyanide added to the resulting imine, the diastereomeric mixture thus produced hydrolyzed to the carboxamides (15) which were found to be separable by fractional crystallization or chromatography. The pKa values of the β-aryl-β,β-difluoroalanines (4) were measured and biological profile of the latter probed. 3-(4-Chlorophenyl)-3,3-difluoro-2-oxopropionic acid (4c) proved to be a potent (Ki 27 μM) and selective inhibitor of arogenate dehydratase, a key enzyme catalyzing the last step of the phenylalanine biosynthesis.
- Schlosser, Manfred,Brügger, Nadia,Schmidt, Werner,Amrhein, Nikolaus
-
p. 7731 - 7742
(2007/10/03)
-
- Synthesis of γ-Fluoro-α,β-unsaturated Carboxylic Esters from Saturated α-Fluoro Aldehydes
-
γ-Fluoro-α,β-unsaturated carboxylic esters 7a, 7b and 7d and 4-fluoro-4-phenylbut-3-enoic ester (8) are obtained by two alternative pathways from 2-fluoro aldehydes 5a-d, either by Horner-Wadsworth-Emmons reaction or by Wittig reaction. The aldehydes 5a-d are prepared by Swern oxidation of the corresponding fluorohydrins 4a-d. These are available from α-olefins by bromofluorination, bromine-by-acetate replacement and subsequent hydrolysis.
- Oldendorf, Jens,Haufe, Gu?nter
-
-