Selective Defluorination Approach to N-Cbz-3,3-difluoro-2-difluoromethylenepyrrolidine and Its Application to 3,3-Difluoroproline Dipeptide Synthesis

Abstract

Mg-promoted defluorination of N-(p-methoxyphenyl)bis(trifluoromethyl)imine 1 gave perfluoroenamine 2, which was readily transformed to N-Cbz-2-trifluoromethyl-3,3-difluoropyrrolidine 10. Chemoselective defluorination from the trifluoromethyl group of 10 by LHMDS-promoted dehydrofluorination in THF provided 3,3-difluoro-2-difluoromethylenepyrrolidine 11. The product 11 was converted to 3,3-difluoroproline dipeptides 16 upon treatment with aminoesters.

Synthesis of Quaternary‐Carbon‐Containing and Functionalized Enantiopure Pentanecarboxylic Acids from Biocatalytic Desymmetrization of meso‐Cyclopentane‐1,3‐Dicarboxamides

“…For example,s imple and practical chemical manipulations of amide and ester functionalg roups of 30 would provides traightforward routes to diversec arba-sugar containing nucleoside analogues. [10] To demonstrate the utility of the method, the synthesis of cyclopentane-fused d-lactam 31 and d-lactone 32 was attempted from biotransformation products.A ss hown in Scheme 7, ozonolysis of 30 a followedc onsecutively by cyclic condensation [18] and reduction [19] led to the formation of dlactam product 31 in 76 %y ield. Cyano-substituted methyl ester (À)-28 underwent saponification with LiOH in am ixture of methanol and water,a nd subsequent iodolactonization under basic conditions to afford d-lactoned erivative 32 as nearly the sole product with ad iastereomericr atio of greater than 20:1.…”

Trifluoromethyl nitrogen heterocycles: synthetic aspects and potential biological targets

“…22). 84 At the same time, fluorinated amines 121a,b were produced in B55% yields by reaction of xanthate 122 with olefins 123 in the presence of lauroyl peroxide in refluxing 1,2-dichloroethane (DCE). The subsequent cyclization with potassium tertbutoxide in THF provided the fluorinated heterocycles 124 in B45% yields as mixtures of diastereomers.…”

Synthesis of 2-Fluoro-1,4-benzoxazines and 2-Fluoro-1,4-benzoxazepin-5-ones by Exploring the Nucleophilic Vinylic Substitution (SNV) Reaction of gem-Difluoroenamides

“…A significant amount of research has already been devoted to the class of β,β-dihaloenamines and β,β-dihalogenated enamides . In contrast, while some difluorinated enamines have been used as building blocks, for example, in the synthesis of difluorocysteine and -serine derivatives, dipeptides, difluoro­imines, and various α,α-difluoro-β-hydroxycarbonyl compounds, the chemistry of difluoroenamides has received only very limited attention. To our knowledge, this reactivity was exploited only twice toward the synthesis of fluorinated heterocycles, more specifically toward isoxazolidines and dihydropyrans or oxazoles .…”