A stereoselective one-pot synthesis of spiropyrazolones through an organocatalytic
asymmetric Michael addition and a formal Conia-ene reaction has been developed.
Depending on the nitroalkene, the 5-exo-dig-cyclization could be achieved by
silver-catalyzed alkyne activation or by oxidation of the intermediate enolate. The
mechanistic pathways have been investigated using computational chemistry and
mechanistic experiments.
As tereoselective one-pot synthesis of spiropyrazolones through an organocatalytic asymmetric Michael addition and aformal Conia-ene reaction has been developed. Depending on the nitroalkene,t he 5-exo-dig-cyclization could be achieved by silver-catalyzed alkyne activation or by oxidation of the intermediate enolate.T he mechanistic pathways have been investigated using computational chemistry and mechanistic experiments.
This review covers the enantioselective lithiation–substitution at the α‐position of nitrogen‐containing heterocycles mediated by strong organolithium bases and chiral ligands. The reactions occur by two main mechanistic pathways: asymmetric deprotonation and asymmetric substitution. For
N
‐Boc heterocycles, asymmetric deprotonation is the predominant pathway, and
s
‐BuLi, in combination with chiral diamines, such as (–)‐sparteine and the (+)‐sparteine surrogate, are used. This approach is highly successful with
N
‐Boc pyrrolidines, piperidines, and piperazines. Substrates for asymmetric‐substitution‐mediated reactions include some
N
‐Boc heterocycles, but other
N
‐substituents, such as
N
‐alkyl groups,
N
‐alkyl‐BY
3
salts (Y = H, F) and
N
‐thioamide groups are also used. With both mechanistic pathways, the lithiated heterocycle can be transmetalated to form an organocopper or organozinc species to widen the scope of the electrophile. The full scope and limitations of this approach to synthesize enantioenriched α‐substituted aziridines, azetidines, pyrrolidines, piperidines, piperazines, azepanes and other five‐/six‐membered‐ring heterocyles are summarized.
Asymmetric Synthesis of Spiropyrazolones by Sequential Organo-and SilverCatalysis. -An asymmetric Michael addition and a formal Conia-ene reaction give rise to a stereoselective one-pot synthesis of spiropyrazolones. Depending on the nitroalkene, the 5-exo-dig-cyclization is achieved by silver-catalyzed alkyne activation or by oxidation of the intermediate enolate. This method overcomes some limitations of established spiropyrazolone syntheses. -(HACK, D.; DUERR, A. B.; DECKERS, K.; CHAUHAN, P.; SELING, N.; RUEBENACH, L.; MERTENS, L.; RAABE, G.; SCHOENEBECK*, F.; ENDERS, D.; Angew.
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