Enantioselective Aza‐Michael Addition of Imides by Using an Integrated Strategy Involving the Synthesis of a Family of Multifunctional Catalysts, Usage of Multiple Catalysis, and Rational Design of Experiment

Silvi, Mattia; Renzi, Polyssena; Rosato, Deborah; Margarita, Cristiana; Vecchioni, Alessio; Bordacchini, Ivan; Morra, Diego; Nicolosi, Alessandro; Cari, Riccardo; Sciubba, Fabio; Schietroma, Daniele M. Scarpino; Bella, Marco

doi:10.1002/chem.201301493

Cited by 23 publications

(14 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The concentration of sample for CD analysis was 0.37 mg/mL (MeOH). The analytical data are in agreement with those reported previously in the literature [ 83 ].…”

Section: Methodssupporting

confidence: 91%

Synthesis of Isothiocyanates Using DMT/NMM/TsO− as a New Desulfurization Reagent

2021

View full text Add to dashboard Cite

Thirty-three alkyl and aryl isothiocyanates, as well as isothiocyanate derivatives from esters of coded amino acids and from esters of unnatural amino acids (6-aminocaproic, 4-(aminomethyl)benzoic, and tranexamic acids), were synthesized with satisfactory or very good yields (25–97%). Synthesis was performed in a “one-pot”, two-step procedure, in the presence of organic base (Et3N, DBU or NMM), and carbon disulfide via dithiocarbamates, with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TsO−) as a desulfurization reagent. For the synthesis of aliphatic and aromatic isothiocyanates, reactions were carried out in a microwave reactor, and selected alkyl isothiocyanates were also synthesized in aqueous medium with high yields (72–96%). Isothiocyanate derivatives of L- and D-amino acid methyl esters were synthesized, under conditions without microwave radiation assistance, with low racemization (er 99 > 1), and their absolute configuration was confirmed by circular dichroism. Isothiocyanate derivatives of natural and unnatural amino acids were evaluated for antibacterial activity on E. coli and S. aureus bacterial strains, where the most active was ITC 9e.

show abstract

“…The concentration of sample for CD analysis was 0.37 mg/mL (MeOH). The analytical data are in agreement with those reported previously in the literature [ 83 ].…”

Section: Methodssupporting

confidence: 91%

Synthesis of Isothiocyanates Using DMT/NMM/TsO− as a New Desulfurization Reagent

2021

View full text Add to dashboard Cite

show abstract

“…Jørgensen and co‐workers reported the use of 1,2,4‐triazoles as good amine surrogates for secondary‐amine‐catalyzed enantioselective aza‐Michael reactions with α,β‐unsaturated aldehydes 6. Nonbasic benzotriazoles,7 5‐phenyltetrazoles,8 hydroxylamines,9 hydrazones,10 azides,11 anilines,12 hydrazides,13 imides,14 and imines15 have also been reported as valid nitrogen sources for asymmetric aza‐Michael reactions under iminium catalysis. Ooi and co‐workers reported a unique arylaminophosphonium‐catalyzed asymmetric addition of 2,4‐dimethoxyanilines to nitroolefins 16…”

Section: Methodsmentioning

confidence: 99%

Highly Enantioselective Aza‐Michael Reaction between Alkyl Amines and β‐Trifluoromethyl β‐Aryl Nitroolefins

2015

View full text Add to dashboard Cite

The aza-Michael addition reaction is av ital transformation for the synthesis of functionalizedc hiral amines. Despite intensive research, enantioselective aza-Michael reactions with alkyl amines as the nitrogen donor have not been successful. We report the use of chiral N-heterocyclic carbenes (NHCs) as noncovalent organocatalysts to promote ah ighly selective aza-Michael reaction between primary alkyla mines and b-trifluoromethyl b-aryl nitroolefins.I nc ontrast to classical conjugate-addition reactions,astrategy of HOMOraising activation was used. Chiral trifluoromethylated amines were synthesized in high yield (up to 99 %) with excellent enantioselectivity (up to 98 %ee).The asymmetric aza-Michael reaction is arguably one of the most straightforward methods for the synthesis of important 1,2-difunctionalized chiral building blocks,s uch as 1,2-diamines. [1] Many successful combinations of nitrogen nucleophiles and electron-deficient olefins have been reported, with either Lewis acid catalysts [2] or organocatalysts. [3] However, two key problems remain largely unsolved:t he use of alkyl amines as the nitrogen source,and the construction of tertiary stereocenters with anitrogen substituent. Simple alkyl amines tend to form stable complexes with Lewis acids,w hich not only deactivates the catalyst, but also renders the aza-Michael reaction reversible. [4] In the case of organocatalysis,p rimary and secondary amines interfere with both LUMO-lowering iminium activation (competing imine/iminium formation) and proton catalysis (acid-base neutralization). As ar esult, research efforts have been mostly concentrated on modulating the basicity of the donor nitrogen atom (Scheme 1). For example,M acMillan and co-workers used N-silyloxycarbamates as anonbasic nitrogen source for aza-Michael reactions of a,b-unsaturated aldehydes. [5] Jørgensen and co-workers reported the use of 1,2,4-triazoles as good amine surrogates for secondary-amine-catalyzed enantioselective aza-Michael reactions with a,b-unsaturated aldehydes. ] and imines [15] have also been reported as valid nitrogen sources for asymmetric aza-Michael reactions under iminium catalysis.Ooi and co-workers reported au nique arylaminophosphonium-catalyzed asymmetric addition of 2,4-dimethoxyanilines to nitroolefins. [16] Theonly reaction of this type involving abasic amine was reported by Sundararajan and Prabagaran, who used ap olymer-supported Lewis acid as the catalyst and found that benzyl amine reacted with ethyl cinnamate to give the product with 81 % ee. [17] However,t he arguably more useful reaction of unactivated alkyl amines has not been reported. Furthermore,n early all aza-Michael reactions rely on LUMO-lowering activation mechanisms with Lewis acids, amine catalysts,o rB r ønsted acids.H erein, we report an enantioselective aza-Michael reaction between primary alkyl amines and b-trifluoromethyl b-aryl nitroolefins for the Entry Catalyst Additive Solvent Yield [%] [b] ee [%] [c]

show abstract

“…Sigman applied surface response modelling to optimise ligands for metal‐catalysed asymmetric allylation and asymmetric propargylation 6. Recently, our research group applied DoE to optimise the reaction conditions for a challenging aza‐Michael addition of imides mediated by multifunctional and multiple catalysis 7. To the best of our knowledge, there is only one report to date on kinetic resolution and statistical optimisation.…”

Section: Introductionmentioning

confidence: 99%

Kinetic Resolution of Oxazinones: Rational Exploration of Chemical Space through the Design of Experiments

Renzi

Kronig

Carlone

et al. 2014

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

show abstract

Enantioselective Aza‐Michael Addition of Imides by Using an Integrated Strategy Involving the Synthesis of a Family of Multifunctional Catalysts, Usage of Multiple Catalysis, and Rational Design of Experiment

Cited by 23 publications

References 56 publications

Synthesis of Isothiocyanates Using DMT/NMM/TsO− as a New Desulfurization Reagent

Synthesis of Isothiocyanates Using DMT/NMM/TsO− as a New Desulfurization Reagent

Highly Enantioselective Aza‐Michael Reaction between Alkyl Amines and β‐Trifluoromethyl β‐Aryl Nitroolefins

Kinetic Resolution of Oxazinones: Rational Exploration of Chemical Space through the Design of Experiments

Contact Info

Product

Resources

About