Nucleophilic reactions of ethyl (Z)-2‑bromo-4,4,4-trifluorobut-2-enoate: One molecule – various heterocycles

Aza‐Michael Reaction: A Decade Later – Is the Research Over?

“…This conclusion can be illustrated by recent examples of the uncatalyzed aza-Michael reaction with geminal [22] or vicinal substituted alkenes. [23][24][25][26][27] For example, arylidene malonic acid diethyl esters 13 react quickly (unfortunately, the time is not specified) with various secondary amines as well as pyrazoles under non-catalytic conditions to provide expected adduct 14 in good to high yields (Scheme 3). [22] The addition of amines to unsaturated diazoketones 15 is proved to be very dependent on the type of Michael acceptor and amine nature (Scheme 4).…”

Pull‐Pull Alkenes in the Aza‐Michael Reaction

“…In contrast, only 5‐hydroxypyrazole 56 (R=Bn) was isolated in moderate yield (31%) when the same ester 52 a was treated with benzylhydrazine (Scheme 22). [62] …”

“…[63] The reaction of bromoenoate 52 a with other 1,4-binucleophiles (diamines, aminoalcohols and aminothiol) led to various six-and five-membered heterocycles some of them are privileged structures for medicinal chemistry and can be easily prepared by one-pot procedure in good yield (Scheme 23). [62] The role of the β-CF 3 substituent became clear in compare the reactivity of enoates 52 a,b and its nonfluorinated analogues -alkyl 2-bromobut-2-enoates. It was shown that very often under the conditions which was found optimal for CF 3 -bromoenoate 52 a (TEA, THF or EtOH, rt), no reaction occurred when methyl 2-bromobut-2-enoates was treated with the same nucleophiles (AdNH 2 , BnNH 2 , DMEDA).…”

“…The reaction of bromoenoate 52 a with other 1,4‐binucleophiles (diamines, aminoalcohols and aminothiol) led to various six‐ and five‐membered heterocycles some of them are privileged structures for medicinal chemistry and can be easily prepared by one‐pot procedure in good yield (Scheme 23). [62] …”

“…[51] In contrast, only 5hydroxypyrazole 56 (R=Bn) was isolated in moderate yield (31%) when the same ester 52 a was treated with benzylhydrazine (Scheme 22). [62] The optically pure CF conditions. [63] The reaction of bromoenoate 52 a with other 1,4-binucleophiles (diamines, aminoalcohols and aminothiol) led to various six-and five-membered heterocycles some of them are privileged structures for medicinal chemistry and can be easily prepared by one-pot procedure in good yield (Scheme 23).…”