8 research outputs found
Generation and Ring Opening of Aziridines in Telescoped Continuous Flow Processes
A simple method for
the preparation of a variety of <i>N</i>-sulfonyl aziridines
(10 examples) from 1,2-amino alcohols under
continuous flow conditions is described. Using flow based methods,
the aziridines can be further ring opened with oxygen, carbon, and
halide nucleophiles or ring expanded to imidazolines by Lewis acid
promoted reaction with nitriles. Telescoping the aziridine generation
and ring opening steps together in a microfluidic reactor allows the
chemistry to be undertaken with limited exposure to the potentially
hazardous aziridine intermediates
Generation and Ring Opening of Aziridines in Telescoped Continuous Flow Processes
A simple method for
the preparation of a variety of <i>N</i>-sulfonyl aziridines
(10 examples) from 1,2-amino alcohols under
continuous flow conditions is described. Using flow based methods,
the aziridines can be further ring opened with oxygen, carbon, and
halide nucleophiles or ring expanded to imidazolines by Lewis acid
promoted reaction with nitriles. Telescoping the aziridine generation
and ring opening steps together in a microfluidic reactor allows the
chemistry to be undertaken with limited exposure to the potentially
hazardous aziridine intermediates
Palladium-Catalyzed Multicomponent Synthesis of 2âAryl-2-imidazolines from Aryl Halides and Diamines
An
efficient palladium-catalyzed three-component reaction that
combines aryl halides, isocyanides, and diamines provides access to
2-aryl-2-imidazolines in yields up to 96%. Through variation of the
diamine component, the reaction can be extended to the synthesis of
2-aryl-1<i>H</i>-benzimidazoles and 2-aryl-1,4,5,6-tetrahydropyrimidines
Palladium-Catalyzed Multicomponent Synthesis of 2âAryl-2-imidazolines from Aryl Halides and Diamines
An
efficient palladium-catalyzed three-component reaction that
combines aryl halides, isocyanides, and diamines provides access to
2-aryl-2-imidazolines in yields up to 96%. Through variation of the
diamine component, the reaction can be extended to the synthesis of
2-aryl-1<i>H</i>-benzimidazoles and 2-aryl-1,4,5,6-tetrahydropyrimidines
Asymmetric Synthesis of 2âSubstituted Oxetan-3-ones via Metalated SAMP/RAMP Hydrazones
2-Substituted oxetan-3-ones can be
prepared in good yields and
enantioselectivities (up to 84% ee) by the metalation of the SAMP/RAMP
hydrazones of oxetan-3-one, followed by reaction with a range of electrophiles
that include alkyl, allyl, and benzyl halides. Additionally, both
chiral 2,2- and 2,4-disubstituted oxetan-3-ones can be made in high
ee (86â90%) by repetition of this lithiation/alkylation sequence
under appropriately controlled conditions. Hydrolysis of the resultant
hydrazones with aqueous oxalic acid provides the 2-substituted oxetan-3-ones
without detectable racemization
Nitrogen Stereodynamics and Complexation Phenomena as Key Factors in the Deprotonative Dynamic Resolution of Alkylideneaziridines: A Spectroscopic and Computational Study
The present work is aimed at shedding
light on the origin of the
stereoselectivity observed in the reactions of chiral heterosubstituted
organolithiums, generated by lithiation of alkylideneaziridines. Factors
such as the nitrogen inversion barrier, the stereochemistry at the
nitrogen atom, the substitution pattern of the alkylideneaziridines,
and the reaction conditions are taken into consideration. The interplay
between nitrogen stereodynamics and complexation phenomena seems to
be crucial in determining the stereochemical outcome of the lithiation/trapping
sequence. The findings were rationalized by a synergistic use of NMR
experiments, run on the lithiated intermediates, alongside computational
data. It has been demonstrated that, in such systems, the stereochemistry-determining
step is the deprotonation reaction, and a model based on a deprotonative
dynamic resolution has been proposed. Such findings could find application
in dynamic systems other than aziridines
Synthesis and functionalization of azetidineâcontaining small macrocyclic peptides
Cyclic peptides are increasingly important structures in drugs but their development can be impeded by difficulties associated with their synthesis. Here, we introduce the 3âaminoazetidine (3âAAz) subunit as a new turnâinducing element for the efficient synthesis of small headâtoâtail cyclic peptides. Greatly improved cyclizations of tetraâ, pentaâ and hexapeptides (28 examples) under standard reaction conditions are achieved by introduction of this element within the linear peptide precursor. Postâcyclization deprotection of the amino acid side chains with strong acid is realized without degradation of the strained fourâmembered azetidine. An special feature of this chemistry is that further lateâstage modification of the resultant macrocyclic peptides can be achieved via the 3âAAz unit.  This is done by: (i) chemoselective deprotection and substitution at the azetidine nitrogen, or by (ii) a clickâbased approach employing a 2âpropynyl carbamate on the azetidine nitrogen. In this way, a range of dye and biotin tagged macrocycles are readily produced. Structural insights gained by XRD analysis of a cyclic tetrapeptide indicate that the azetidine ring encourages access to the less stable, allâtrans conformation. Moreover, introduction of a 3âAAz into a representative cyclohexapeptide improves stability towards proteases compared to the homodetic macrocycle.</p
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Synthesis and functionalization of azetidineâcontaining small macrocyclic peptides
Cyclic peptides are increasingly important structures in drugs but their development can be impeded by difficulties associated with their synthesis. Here, we introduce the 3âaminoazetidine (3âAAz) subunit as a new turnâinducing element for the efficient synthesis of small headâtoâtail cyclic peptides. Greatly improved cyclizations of tetraâ, pentaâ and hexapeptides (28 examples) under standard reaction conditions are achieved by introduction of this element within the linear peptide precursor. Postâcyclization deprotection of the amino acid side chains with strong acid is realized without degradation of the strained fourâmembered azetidine. An special feature of this chemistry is that further lateâstage modification of the resultant macrocyclic peptides can be achieved via the 3âAAz unit.  This is done by: (i) chemoselective deprotection and substitution at the azetidine nitrogen, or by (ii) a clickâbased approach employing a 2âpropynyl carbamate on the azetidine nitrogen. In this way, a range of dye and biotin tagged macrocycles are readily produced. Structural insights gained by XRD analysis of a cyclic tetrapeptide indicate that the azetidine ring encourages access to the less stable, allâtrans conformation. Moreover, introduction of a 3âAAz into a representative cyclohexapeptide improves stability towards proteases compared to the homodetic macrocycle.</p