Imines monofluorination

Nonactivated C—H bonds in imines can be selectively monofluorinated in HF-SbF5 in the presence of CC14 to yield the corresponding fluoroketones when the reaction mixture is quenched with HF-pyridine534 (Scheme 5.54). The transformation is initiated by hydride abstraction with CC13+ from the most reactive carbon farthest from the functional group and involves dicationic intermediates 134 and 135. 

A solution of Tf2NF (360 mg, 1.2 mmol) in anhyd CHjClj (5 mL) was stirred with aiihyd NajCOj (0.1 g) for 15 min, A solution of A-[l-(4-bromophenyl)cthylidene]butylamine (130 mg, 0.5 mmol) in CH Cl, (5 mL) was then added dropwise with stirring at rt. The resulting solution was stirred for 5 h, then 1 M aq HCl (20 mL) was poured into the mixture. The organic layer was separated and the aqueous phase was extracted with Et O (3 x 20 mL), The combined extracts were washed with brine and dried (Na SO. ), and the solvent was removed with a rotary evaporator. The residue w as flash chromatographed (pentane/ Ei,0 30 1) to give the pure difluoro product yield 90 mg (78%). When the same imine was reacted with 0.67 equivalents of TfjNF, monofluorinated ketone 2 was obtained in about 30% yield, in addition to 16% of the difluorinated ketone. In the latter reaction, the imine solution has to be added to the. V-fluoro amine solution in one portion to increase the amount of monofluorinated product. 

The first section of this chapter describes the preparation and several synthetic applications of a-fluoroalkyl P-sulfmyl enamines and imines the second deals with the chemistry of di- and trifluoropyruvaldehyde A, 5-ketals, stereochemically stable synthetic equivalents of P-di and P-trifluoro a-amino aldehydes, which can be prepared from the corresponding p-sulfinyl enamines the third overviews the preparation of chiral sulfinimines of trifluoropyruvate and their use to prepare a library of a-trifluoromethyl (Tfm) a-amino acids the fourth section is mainly dedicated to the asymmetric synthesis of monofluorinated amino compounds, using a miscellany of methods such as MifstmobuAike azidation of P-hydroxy sulfoxides, ring opening of fluoroalkyl epoxides with nitrogen-centered nucleophiles and 1,3-dipolar cycloadditions with chiral fluorinated dipolarophiles. 

Route B is also versatile and efficient (/-/,/5), allowing for the preparation of iV-aryl, A -alkoxycarbonyl and also A -unsubstituted polyfluoroalkyl enamines and imines in good to excellent yields. Starting material in this case are fluorinated p-sulfmyl ketones 7, which were submitted to Staudmger (aza-PP/7%) reaction 16,17) with iminophosphoranes 8. Monofluorinated ketones 7 were found to be poorly reactive when submitted to the Staudinger reaction, therefore low yields (10-30%) of the corresponding products were generally obtained. No reaction was achieved with nonfluorinated 3-ketosulfoxides. 

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