Synthesis of α,α-difluoro-β-amino carbonyl-containing sulfonamides and related compounds

Recent Progress in the in situ Detrifluoro­acetylative Generation of Fluoro Enolates and Their Reactions with Electrophiles

“…According to the reported data,32a,32b the reactivity of the enolates 26 generated in situ by detrifluoroacetylation turned out to be relatively low. Thus, no reactions were observed between 26 and non‐activated imines derived from benzaldehyde and aniline or its 4‐OMe‐ or 4‐CO 2 Me‐substituted derivatives.…”

“…Although the CF 2 ‐containing sulfonamides 28 are a quite interesting class of biologically relevant compounds, their synthetic applications as intermediates are rather limited due to the problematic nature of the removal of the sulfonamide function. Therefore, the same research group32b studied the reactions between enolates 26 and other types of imines.…”

Catalytic Enantioselective Michael Addition Reactions of Tertiary Enolates Generated by Detrifluoroacetylation

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This work describes, for the first time, Michael additionr eactions of tertiary fluoro-enolates in situ generated by detrifluoroacetylation with 1-(1-(phenylsulfonyl) vinylsulfonyl)benzene. While it is still premature to draw any definite conclusion about reactivity of these enolates generated in situ by detrifluoroacetylation, the available data [11][12][13][14][15][16][17][18][19][20] point to the necessity to use highly electrophilic reaction partners.F or example, enolates 4 do not react at all with unactivated imines [16a] and ketones. These reactions show ac onsiderable degree of structuralg eneralitya nd allow the preparation of new types of biologically relevant molecules that contain quaternaryC ÀFstereogenic carbonatomsand feature five-, six-, or seven-membered rings as well as heterocyclic 3-fluoro-2,3-dihydrochromen-4-one moieties.

Development of new efficient methodsf or the synthesis of fluorine-containing compounds remainso ne of the central challenges of modern organic chemistry.

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“…Over the years, the fluorinatedb uilding-block approach was shown to be synthetically reliablea nd functional as ag roup-diverse strategyf or the preparation of structurally complex molecules of medicinal importance. [6,7] As presented in Scheme 1, three general structural types of enolate precursors 1, [6,8] 2, [9] and 3 [10] have been introduceds o far.I nt he presence of organic base (usually triethylamine) and metali ons (usually LiBr) compounds 1-3 readily undergo in situ elimination of trifluoroacetic acid and generationo fc orresponding enolates 4.C hemistry of these enolates has been studied on the examples of halogenation, [11] aldol [12][13][14][15] and Mannich [16][17][18][19][20] addition reactions. [5] One of the recent innovations in this chemistryw as the development of a detrifluoroacetylative approach fort he in situ generation of fluoro-enolates (Scheme 1).…”

“…[4] In this area, fluorine-containing enols are particularly attractive structural units displaying versatile reactivity and target molecular diversity. While it is still premature to draw any definite conclusion about reactivity of these enolates generated in situ by detrifluoroacetylation, the available data [11][12][13][14][15][16][17][18][19][20] point to the necessity to use highly electrophilic reaction partners.F or example, enolates 4 do not react at all with unactivated imines [16a] and ketones. [6,7] As presented in Scheme 1, three general structural types of enolate precursors 1, [6,8] 2, [9] and 3 [10] have been introduceds o far.I nt he presence of organic base (usually triethylamine) and metali ons (usually LiBr) compounds 1-3 readily undergo in situ elimination of trifluoroacetic acid and generationo fc orresponding enolates 4.C hemistry of these enolates has been studied on the examples of halogenation, [11] aldol [12][13][14][15] and Mannich [16][17][18][19][20] addition reactions.…”