Diastereoselective Synthesis of the Nonracemic Methyl syn-(3-Fluoroalkyl)isoserinates

Abstract

Cycloaddition of the (fluoroalkyl)imines 7a-c with the ketene formed in situ from (benzyloxy)acetyl chloride and triethylamine provided stereoselectively cis-(fluoroalkyl)azetidinones 5a-c in moderate yields. The corresponding N-Boc-isoserinates 11a-c and protected synthons 12a-c have been prepared from these azetidinones 5a-c. Cycloaddition of the chiral imine 18 (R F ) CF 3 ) with the same ketene led to the diastereoisomeric azetidinones 19 and 20 with a poor diastereoisomeric excess (10-20%). However, the two diastereoisomers could be easily separated by crystallization and provided enantiomerically pure N-Boc-isoserinates 23 (R,R) and 23 (S,S) after ring opening and debenzylation.

Trifluoroacetaldehyde: A useful industrial bulk material for the synthesis of trifluoromethylated amino compounds

“…However, its adaptation to trifluoroacetaldehyde has received little attention. First, we attempted to prepare trifluoroethylamino derivatives via reduction of trifluoroacetaldimine 3, which was synthesized according to the conventional method [20]. Trifluoroacetaldimine 3a, derived from p-anisidine 2a, was easily reduced by catalytic hydrogenation using Pd-C catalyst to produce trifluoroethylamine 4a in 90% yield (Scheme 1).…”

New synthesis of 2-trifluoromethyl-2,3-dihydro-1H-quinolin-4-ones

“…As reported in the literature [11], imine 1 and N,Odisubstituted aminal 2a were generated competitively when equivalent amounts of 4-anisidine and trifluoroacetaldehyde ethyl hemiacetal (TFAE) were refluxed in toluene in the presence of a catalytic amount of p-toluenesulfonic acid (Scheme 1, Eq. (1)).…”

Trifluoromethyl- and difluoromethyl-β-lactams as useful building blocks for the synthesis of fluorinated amino acids, dipeptides, and fluoro-taxoids

“…Accordingly, it was necessary to use benzyloxyacetyl chloride as the ketene precursor for the reaction with CF 3 -imine 7. The use of benzyloxyketene for the reaction with CF 3 -imines has been reported by us [48,51] and others [40]. Thus, the [2 þ 2] ketene-imine cycloaddition proceeded smoothly at 40 8C to give racemic cis-3-benzyloxy-4-trifluoromethylazetidin-2-one 8(AE) in moderate yield.…”

“…Therefore, fluorine-containing a-hydroxy-b-amino acids are expected to serve as important and useful bioactive compounds for medicinal chemistry and chemical biology. However, only a limited number of methods for the synthesis of enantiopure fluorine-containing a-hydroxy-b-amino acids have been reported to date [32,[36][37][38][39][40].…”