1395349-05-9Relevant academic research and scientific papers
The dual reactivity of Weinreb amides applied to the late-stage divergent functionalisation of: Meso pyrrolidines
Boufroura, Hamza,Sevaille, Laurent,Gigant, Nicolas,Drège, Emmanuelle,Joseph, Delphine
, p. 12403 - 12411 (2018)
By exploiting the dual reactivity of a Weinreb amide moiety, i.e. nucleophilic addition or N-O reductive cleavage, a series of diversified symmetrical and dissymmetrical pyrrolidine analogues of lobelanine were synthesized from simple and readily available building blocks. Diversity is introduced at a late stage by using a wide variety of readily available organolithium and organomagnesium reagents, and chemoselective orientation can be achieved due to the steric encumbrance of both the reaction partners, the liganding ability of the starting meso pyrrolidine, and the nature of the organometallic species. This work constitutes the first example that takes advantage of the side reaction of Weinreb amide decomposition for the desymmetrization of a meso platform bearing two remote and highly flexible N-methoxy-N-methylamide arms through a probable beneficial metal-templated arrangement.
Thermodynamic epimeric equilibration and crystallisation-induced dynamic resolution of lobelanine, norlobelanine and related analogues
Amara,Bernadat,Venot,Retailleau,Troufflard,Drge,Le Bideau,Joseph
, p. 9797 - 9810 (2015/01/08)
The step-economical synthesis of lobelanine involving a ring closing double aza-Michael (RCDAM) reaction is revisited and successfully extended to the synthesis of various configurationally more stable analogues. Owing to the presence of a configurationally labile β-aminoketone subunit, lobelanine is prone to self-catalyze mutarotation in solution. Through the synthesis of original lobelanine analogues, we studied the influence of (i) the size of the central heterocycle, (ii) the bulkiness of the nitrogen protecting group, and (iii) the phenacyl arm substituent on the thermodynamic equilibrium and its displacement by crystallisation-induced dynamic resolution (CIDR). We demonstrated that fine structural tuning combined with optimized CIDR conditions favours the first efficient diastereoselective synthesis of lobelanine's analogues.
Solvent-free double aza-Michael under ultrasound irradiation: Diastereoselective sequential one-pot synthesis of pyrrolidine Lobelia alkaloids analogues
Amara, Zacharias,Drège, Emmanuelle,Troufflard, Claire,Retailleau, Pascal,Joseph, Delphine
experimental part, p. 7148 - 7157 (2012/10/08)
Novel 2,5-meso-pyrrolidines have been straightforwardly synthesized from readily available symmetrical double Michael acceptors. The key step rested on an aza-Michael addition of primary alkylamines to bis-enones. Competitive Rauhut-Currier and aza-Michael reactions have been highlighted in protic solvent. Ultrasound activation associated with solvent-free conditions led to the expected pyrrolidines in quantitative yields and excellent stereoselectivities. The optimized conditions have been extended to the sonochemical synthesis of pyrrolidine Lobelia alkaloids analogues in short sequences.
