Chiral phosphoric acids are efficient organocatalysts for the asymmetric three-component reaction of amines, aldehydes, and pyruvate derivatives. Simultaneous condensation of amines with both carbonylic compounds followed by a hydrogen bonding activated nucleophilic addition of enamines to imines affords densely functionalized enantioenriched 1,5-dihydro-2H-pyrrol-2-ones. These substrates can be used in subsequent diastereoselective transformations to afford enantiopure γ-lactam derivatives.
Chiral
phosphoric acids efficiently catalyze the asymmetric Friedel–Crafts
reaction of several indoles with α-iminophosphonates to
afford enantioenriched hybrid α-aminophosphonate functionalized
indole derivatives.
An efficient synthetic methodology for the preparation of 3-amino 1,5-dihydro-2H-pyrrol-2-ones through a multicomponent reaction of amines, aldehydes, and pyruvate derivatives is reported. In addition, the densely substituted lactam substrates show in vitro cytotoxicity, inhibiting the growth of carcinoma human tumor cell lines HEK293 (human embryonic kidney), MCF7 (human breast adenocarcinoma), HTB81 (human prostate carcinoma), HeLa (human epithelioid cervix carcinoma), RKO (human colon epithelial carcinoma), SKOV3 (human ovarian carcinoma), and A549 (carcinomic human alveolar basal epithelial cell). Given the possibilities in the diversity of the substituents that offer the multicomponent synthetic methodology, an extensive structure-activity profile is presented. In addition, both enantiomers of phosphonate-derived γ-lactam have been synthesized and isolated and a study of the cytotoxic activity of the racemic substrate vs. its two enantiomers is also presented. Cell morphology analysis and flow cytometry assays indicate that the main pathway by which our compounds induce cytotoxicity is based on the activation of the intracellular apoptotic mechanism.
A Brönsted
acid multicomponent reaction between pyruvate
derivatives, amines, and aldehydes for the preparation of phosphorus
and fluorine substituted γ-lactam derivatives is presented.
Depending on the substitution in the resulting 1,5-dihydro-2H-pyrrol-2-one substrates, the reaction provides enol- or
enamine-derived γ-lactams. Some enantioselective examples of
this reaction are also reported using chiral phosphoric acids as organocatalysts.
Moreover, several synthetic applications of γ-lactam derivatives
are presented including some examples of highly diastereoselective
transformations.
Herein we report
the first alkynylation of quinolones with terminal
alkynes under mild reaction conditions. The reaction is catalyzed
by Cu(I) salts in the presence of a Lewis acid, which is essential
for the reactivity of the system. The enantioselective version of
this transformation has also been explored, and the methodology has
been applied in the synthesis of the enantioenriched tetrahydroquinoline
alkaloid cuspareine.
A wide range of methods for the enantioselective synthesis of α‐aminophosphonic acid derivatives have been developed over the years. Although the most used methodology is the Pudovik reaction, the use of α‐iminophosphonates for the synthesis of optically active α‐aminophosphonates has emerged during the last years. The existing methods for the synthesis of α‐phosphorylated imines and their enantioselective reactions for the synthesis of enantio‐enriched α‐aminophosphonates are summarized in this review.
Here, an enantioselective aza-Reformatsky reaction using acyclic ketimine substrates is presented. Using α-phosphorated ketimines as electrophilic substrates and a simple BINOL-derived ligand, phosphorated analogues of aspartic acid holding chiral tetrasubstituted carbons are efficiently obtained with excellent enantioselectivity through an asymmetric organocatalytic Reformatsky-type reaction. The phosphorated analogues of aspartic acid have been used for the synthesis of phosphorus-containing enantiopure tetrasubstituted β-lactams.
Due to their structural similarity with natural α-amino acids, α-aminophosphonic acid derivatives are known biologically active molecules. In view of the relevance of tetrasubstituted carbons in nature and medicine and the strong dependence of the biological activity of chiral molecules into their absolute configuration, the synthesis of α-aminophosphonates bearing tetrasubstituted carbons in an asymmetric fashion has grown in interest in the past few decades. In the following lines, the existing literatures for the synthesis of optically active tetrasubstituted α-aminophosphonates are summarized, comprising diastereoselective and enantioselective approaches.
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