17 research outputs found
Lithiation of 4-membered heterocycles as useful strategy for the preparation of new molecular scaffolds: addressing the regioselectivity in azetidines and thietanes
Four-membered heterocycles (4-MH) with one or two heteroatoms are of great importance in medicinal chemistry and synthetic organic chemistry. This kind of scaffolds show peculiar structural features, related to the ring âpuckeringâ, and biological properties. Our recent research efforts have been focused on the stereoselective synthesis and functionalization of some 4-MH such as azetidines, thietanes and oxazetidines
Desymmetrization of α-diimines: Synthesis of new 3-(diaziridin-3-yl) oxaziridines
New heterocyclic compounds characterized by the presence of a diaziridine and an oxaziridine ring directly bound were reported. A first desymmetrization reaction of α-diimines using nosyloxycarbamate as aminating agent in a H2O/CH2Cl2 system gives (E)-3-(iminomethyl) diaziridine-1-carboxylates which were further functionalized obtaining the never synthesized before 3-(diaziridin-3-yl)oxaziridines. © 2013 Elsevier Ltd. All rights reserved
Solvent-Free Stereoselective Synthesis of (E)-Trifluoromethyl Imines and Hydrazones
A new, green and efficient strategy for the synthesis of trifluoromethyl ketimines, aldimines, and hydrazones starting from the corresponding trifluoromethyl carbonyl compounds or their hemiacetals is reported. The condensation reactions were performed under solvent-free conditions with a range of amines or hydrazines and proceeded with high stereoselectivity, always giving only the E-isomer in very good yields
Microreactor-Mediated Organocatalysis: Towards the Development of Sustainable Domino Reactions
Microreactor-mediated organocatalysed Michael reactions have been developed. By using a soluble proline-derived catalyst, Michael-type reactions, leading to Îł-nitroketones, have been optimized in homogeneous and continuous-flow conditions. As proof of principle, an integrated microfluidic system able to perform domino processes useful in the preparation of bicyclo[4.4.0]decanes with six contiguous stereogenic centres has been set up
Synthesis of optically active trifluoromethyl substituted diaziridines and oxaziridines
(E)-Trifluoromethyl imines were considered as ideal substrates to be transformed into the corresponding diaziridines by a direct amination reaction with nosyloxycarbamates. The diastereoselective induction was strongly controlled by the N-substituent Similar results were obtained in the epoxidation reactions performed on the same substrates using m-CPBA as oxidant. Starting from enantiopure imines chiral diaziridines or oxaziridines were obtained with very high enantiopurity. (C) 2011 Elsevier Ltd. All rights reserved
Stereoselective synthesis and ROESY 1H NMR study of bidiaziridines
The bisaziridination reaction of symmetric (E-s-trans-E)-α-diimines using ethyl nosyloxycarbamate as aminating agent yields symmetrically functionalized bidiaziridines, under mild conditions. The reactions take place with very high stereoselectivity giving only bidiaziridines with total retention of the starting α-diimine configuration, as determined by NMR measurements. Moreover, only a single pure diastereomer, derived from attack of the aza-anion on the opposite faces of conjugate system was obtained, starting from chiral substrates. ROESY analyses clearly show that all nitrogens have a stable pyramidal conformation, and the absolute configurations of new chiral centers were assigned. © 2012 American Chemical Society
Straightforward access to 4-membered sulfurated heterocycles: introducing a strategy for the single and double functionalization of thietane 1-oxide
A strategy for the stereoselective functionalization of thietane 1-oxide has been developed. Mono (C2 substituted) and doubly (C2, C4 disubstituted) functionalized thietanes have been obtained from the readily available thietane 1-oxide by using the corresponding organometallic intermediates that reacted with electrophiles leaving intact the 4-membered ring
Chiral bidiaziridines by a two-step domino aziridination of meso-α-diimines
Chiral racemic α-diimines, tested in aziridination reactions with NsONHCO2Et, for the first time led to the synthesis of d,l-bidiaziridines, stereoselectively derived from the corresponding meso (E-s-trans-E)-α-diimines. Moreover, a minor bidiaziridine isomer, probably a meso form that was lost under classical work-up conditions, can be obtained by adding water to the crude mixtures at the end of amination reactions. The results definitively prove that the imine aziridination by carbamates is a two-step domino process. The structures of the compounds were determined using 2D NMR on purified bidiaziridine
Deconstruction of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline moiety to separate Pglycoprotein (P-gp) activity from Ï2 receptor affinity in mixed P-gp/Ï2 receptor agents
6,7-Dimethoxytetrahydroisoquinoline is widely used as basic moiety in s2 receptor ligands, in order to
provide s2 versus s1 selectivity. This same moiety is also widely exploited in modulators of P-glycoprotein
(P-gp) efflux pump, so that mixed s2/P-gp agents are often obtained. Deconstruction of 6,7-
dimethoxytetrahydroisoquinoline moiety present in the potent mixed s2/P-gp agent 6,7-dimethoxy-2-
[4-[1-(4-fluorophenyl)-1H-indol-3-yl]butyl]-1,2,3,4-tetrahydroisoquinoline (1) could lead to the separation of s2 affinity from P-gp activity. Therefore, phenethylamino-, benzylamino- and indanamine series
were obtained. The NH group was also methylated in the N-phenethylamino series, and ethylated in the
benzylamino series, to better match 6,7-dimethoxytetrahydroisoquinoline. The s2 affinity drastically
decreased with the increase of conformational freedom, whereas alkylation of the NH-group was beneficial
for s2 receptor interaction. By contrast, deconstruction of 6,7-dimethoxytetrahydroisoquinoline slightly
reduced P-gp activity, with dimethoxy-substituted derivatives displaying potent P-gp interaction. Therefore, âring-openedâ 6,7-dimethoxytetrahydroisoquinoline derivatives represent a promising strategy to
obtain P-gp selective agents devoid of s2 receptor affinit
Regioselective functionalization of 2-arylazetidines: evaluating the ortho-directing ability of the azetidinyl ring and the a-directing ability of the N-substituent
The regioselective lithiationâfunctionalization of 2-arylazetidines
has been explored. The nature of the N-substituent is mainly
responsible for a regioselectivity switch. ortho-Lithiation occurred,
using hexyllithium as a greener base, in N-alkylazetidines, while abenzylic
lithiation has been observed with N-Boc azetidines