NBS‐Mediated Aziridination between Styrenes and Amides under Transition Metal‐Free Conditions

An efficient and simple protocol for N‐bromosuccinimide (NBS)‐mediated styrenes aziridination using amides as the nitrenoid source has been developed. This aziridination affords desired products in moderate to good yields without using transition metal catalyst under very mild reaction condition.     

Cerium(IV) ammonium nitrate: Reagent for the versatile oxidative functionalization of styrenes using N-hydroxyphthalimide

Cerium(IV) ammonium nitrate was found to be a versatile reagent for the oxidative functionalization of styrenes using N-hydroxyphthalimide and iodine affording three different types of products with oxyphthalimide, nitrate and iodide groups. It was shown that reaction of styrenes with N-hydroxyphthalimide and cerium(IV) ammonium nitrate can be selectively directed to oxynitro-oxyphthalimides and dioxyphthalimides depending on the reaction conditions, in particular a solvent. Reaction of styrenes with iodine under the action of N-hydroxyphthalimide and cerium(IV) ammonium nitrate leads to the formation of iodo-oxyphthalimides.     

Tertiary amine-promoted enone aziridination: investigations into factors influencing enantioselective induction

trans-N-Unsubstituted aziridines were synthesised (up to 77% ee) via a chiral tertiary amine-promoted nucleophilic aziridination of α,β-unsaturated ketones utilising in situ generated N–N ylides (aminimines). A wide range of chiral tertiary amines were synthesised and evaluated, allowing structure–activity relationships to be drawn. The most efficient promoter for asymmetric aziridination, quinine, was assessed with several enones to ascertain the effect of substrate structure on product ee, while the intermediate hydrazinium salt was characterised by X-ray crystallography.     

Designed To React: Terminal Copper Nitrenes and Their Application in Catalytic C−H Aminations

Heteroscorpionate ligands of the bis(pyrazolyl)methane family have been applied in the stabilisation of terminal copper tosyl nitrenes. These species are highly active intermediates in the copper‐catalysed direct C?H amination and nitrene transfer. Novel perfluoroalkyl‐pyrazolyl‐ and pyridinyl‐containing ligands were synthesized to coordinate to a reactive copper nitrene centre. Four distinct copper tosyl nitrenes were prepared at low temperatures by the reaction with SO₂tBuPhINTs and copper(I) acetonitrile complexes. Their stoichiometric reactivity has been elucidated regarding the imination of phosphines and the aziridination of styrenes. The formation and thermal decay of the copper nitrenes were investigated by UV/Vis spectroscopy of the highly coloured species. Additionally, the compounds were studied by cryo‐UHR‐ESI mass spectrometry and DFT calculations. In addition, a mild catalytic procedure has been developed where the copper nitrene precursors enable the C?H amination of cyclohexane and toluene and the aziridination of styrenes.     

A one-pot stereoselective synthesis of trans-1-aryl-2-aminotetralins from 2-arylethyl styrenes

An efficient stereoselective synthesis of trans-1-aryl-2-aminotetralins has been achieved via Cu(OTf)₂ catalyzed one-pot aziridination and regioselective intramolecular arylation of in situ generated aziridines from 2-arylethyl styrenes and PhINSO₂(4-NO₂C₆H₄) [PhINNs]. Reaction of a mixture of E/Z-styrenes (?85:15) provided trans-N-protected-1-aryl-2-aminotetralins with high diastereoselectivity (dr > 95:5), which are important synthons for many artificial pharmaceuticals.     

Synthesis of fluorinated N-aminoaziridines: access to new CF3-peptidomimetics

A series of fluorinated N-aminoaziridines have been synthesized by the PhI(OAc)₂-mediated aziridination procedure. The reaction was carried out with various protected hydrazides and fluorinated alkenes. The reaction was extended to alkenes bearing an amino acid and the ring opening of the CF₃–N-aminoaziridines has been investigated.     

N-Bromoamides as versatile catalysts for aziridination of olefins using chloramine-T

N-Bromoamides catalyze effectively the aziridination of electron-deficient as well as electron-rich olefins using chloramine-T (N-chloro-N-sodio-p-toluenesulfonamide) as a nitrogen source under ambient conditions to afford the corresponding aziridines in good to excellent yields.     

Rigid backbone 1,8-anthracene-linked bis-oxazolines (AnBOXes): design,synthesis, application and characteristics in catalytic asymmetric aziridination

A series of rigid backbone 1,8-anthracene-linked bis-oxazolines (AnBOXes) have been designed, synthesized, and evaluated in the catalytic asymmetric aziridination with [N-(p-toluenesulfonyl)imino]phenyliodinane (PhINTs) as a nitrene source. The results indicate that highly enantioselective aziridination of chalcones catalyzed by an AnBOX and CuOTf complex with up to >99% ee and the opposite enantioselectivity, compared with the ligands of Evans et al., can be achieved. The enantioselectivity is substituent dependent with respect to chalcones. Chalcones with electron-donating substituents show higher enantioselectivities due to the stronger Lewis basicity of the oxygen of their carbonyl groups than those with electron-withdrawing substituents. The results also indicate that the coordination between the oxygen of the carbonyl group in chalcones and the ether group in alkenes with the copper in the catalyst is essential for high enantioselectivity, while the π–π stacking interaction between two reactants plays an importantly additional role for high enantioselectivity in asymmetric aziridination. An excellent backbone-controlled stereoselectivity was observed for the AnBOX ligands in asymmetric aziridination, as this will provide very important information for designing novel ligands.     

Synthesis of (−)-benzolactam-V8 by application of asymmetric aziridination

(?)-Benzolactam-V8, an artificially-designed cyclic dipeptide with strong tumor-promoter activity, was synthesized from benzyl (S)-N-(2-formylphenyl)-N-methylvalinate by application of guanidinium ylide-participated asymmetric aziridination followed by the reductive ring-opening reaction of 3-arylaziridine-2-carboxylate formed.     

Aziridination of alkenes using N-iodo-N-potassio-p-toluenesulphonamide as a nitrene precursor

N-Iodo-N-potassio-p-toluenesulphonamide was found to be a convenient nitrene precursor for the aziridination of alkenes in the presence of copper catalysts.     

Microencapsulated Cu(acac)2: a recoverable and reusable polymer-supported copper catalyst for aziridination of olefins

Microencapsulated copper(II) acetylacetonate was prepared and used in the aziridination of alkenes employing [N-(p-tolylsulfonyl)imino]phenyliodinane (PhINTs) as the nitrogen source. Microencapsulated copper(II) acetylacetonate [MC-Cu(acac)₂] catalyst was reused for several cycles with consistent activity.     

Styrene Aziridination by Iron(IV) Nitrides

Thermolysis of the iron(IV) nitride complex [PhB(tBuIm)₃Fe?N] with styrene leads to formation of the high‐spin iron(II) aziridino complex [PhB(tBuIm)₃Fe‐N(CH₂CHPh)]. Similar aziridination occurs with both electron‐rich and electron‐poor styrenes, while bulky styrenes hinder the reaction. The aziridino complex [PhB(tBuIm)₃Fe‐N(CH₂CHPh)] acts as a nitride synthon, reacting with electron‐poor styrenes to generate their corresponding aziridino complexes, that is, aziridine cross‐metathesis. Reaction of [PhB(tBuIm)₃Fe‐N(CH₂CHPh)] with Me₃SiCl releases the N‐functionalized aziridine Me₃SiN(CH₂CHPh) while simultaneously generating [PhB(tBuIm)₃FeCl]. This closes a synthetic cycle for styrene azirdination by a nitride complex. While the less hindered iron(IV) nitride complex [PhB(MesIm)₃Fe?N] reacts with styrenes below room temperature, only bulky styrenes lead to tractable aziridino products.     

Synthesis of substituted pyrrolidines and piperidines from endocyclic enamine derivatives. Synthesis of (±)-laburnamine

Functionalization of the α- and β-positions of readily available endocyclic enamine derivatives provides a convenient method for the formation of substituted pyrrolidines and piperidines. α-Alkoxy-β-iodopyrrolidines are formed by the electrophilic addition of iodine to the endocyclic enamine double bond of an N-substituted 2-pyrroline, and nucleophillic attack by an alcohol on the intermediate iodonium ion. The resultant α-alkoxy-β-iodopyrrolidines can be used in radical cyclization reactions to give bicyclic hemiaminal compounds, which can be further elaborated using N-acyliminium chemistry to form α,β-cis-dialkylsubstituted pyrrolidines. A strategy for the incorporation of amino functionality at the β-position was also established by using iodoamination of the enamine double bond, followed by migration of the amine functionality through an aziridination/methanolysis protocol. An alternative method uses an azidomethoxylation protocol using ceric ammonium nitrate (CAN) in the presence of NaN₃ and methanol. Formation and trapping of the N-acyliminium ions derived from these substrates, afforded the 3-carbamate and 3-azido-2-substituted products with good diastereoselectivity, with the preferential formation of the trans and cis stereoisomers, respectively. Using the sequential iodoamination, aziridination in methanol and N-acyliminium transformation, trans-3-NHCO₂Me-2-allyl-pyrrolidine was prepared, which was used as the key precursor in a synthesis of the natural 1-amidopyrrolizidine alkaloid, (±)-laburnamine.     

Stereoselective synthesis of CF3-substituted aziridines by Lewis acid-mediated aziridination of aldimines with diazoacetates

Treatment of trifluoroacetaldehyde N,O-acetal with diazoacetate in the presence of a Lewis acid furnished CF₃-substituted aziridinecarboxylates in good yields. Both cis and trans isomers were obtained stereoselectively by the proper choice of the ester substituents. Use of a chiral diazoacetate derived from (R)-pantolactone led to highly diastereoselective aziridination (94% de).     

Copper-catalyzed alkene aziridination with N-tosyloxycarbamates

Pyridine copper complexes were found as active catalysts for the intramolecular aziridination of allylic N-tosyloxycarbamates and the intermolecular aziridination of styrenes with trichloroethyl N-tosyloxycarbamates. Free aziridines were easily obtained by basic deprotection of the trichloroethyl group.     

Palladium-catalyzed aziridination of alkenes using N,N-dichloro-p-toluenesulfonamide as nitrogen source

N,N-Dichloro-p-toluenesulfonamide (TsNCl₂) was found to be an efficient nitrogen source for the aziridination of unfunctionalized alkenes using palladium catalysts. Among the palladium salts, palladium acetate was the most effective catalyst for this reaction. A variety of alkenes were reacted at room temperature with TsNCl₂ to form the desired aziridines in moderate to good yields. This method can complement our previous protocol which is limited to the use of electron-deficient α,β-unsaturated alkenes.     

Novel aziridination of α-halo ketones: an efficient nucleophile-induced cyclization of phosphoramidates to functionalized aziridines

A novel and efficient aziridination of α-halo ketones is reported. The reaction of α-halo ketones with diethyl N-arylphosphoramidates affords diethyl N-aryl-N-(2-oxoalkyl)phosphoramidates which undergo reductive (H⁻-induced) cyclization with sodium borohydride followed by sodium hydride to give 1,2-disubstituted and 1,2,3-trisubstituted aziridines. The cyclization induced by NCS⁻ or PhS⁻ affords substituted aziridines functionalized at C-2. The reactions give excellent yields and are highly diastereoselective in favour of cis aziridines.     

Mn-tetraarylporphyrins bearing N-alkyl sulphonamido tails: effect of the length and polarity of the chains on physical properties and reactivity

Manganese-complexes of a new series of tetraarylporphyrins, featuring both chlorine atoms in ortho, ortho′ positions and N-mono- or N,N-disubstituted sulphonamido groups in meta on the meso-phenyls, were used as catalysts in the epoxidation of α-olefines in the presence of diluted (17.5%) H₂O₂ as primary oxidant. The catalytic efficiency of these catalysts is related to the polarity of the chains and the N,N-dialkylsulphonamido porphyrins turned out to be more reactive than the robust Mn-TDClPP in the epoxidations of styrenes.     

Asymmetric aziridination: a new entry to optically active non-N-protected aziridines

A newly designed robust Ru(salen)(CO) complex 3 was found to catalyze asymmetric aziridination using azide compounds carrying p-nitrobenzenesulfonyl and 2-(trimethylsilyl)ethanesulfonyl (SES) groups, which are easily removable N-protecting groups under mild conditions, as a nitrene precursor in a highly enantioselective manner. In particular, the reactions with SES azide showed excellent enantioselectivity greater than 90% ee, except for one example.     

Facile generation of vicinal bromoazides from olefins using TMSN3 and TsNBr2 without any catalyst

A very rapid and efficient method has been developed for the synthesis of vicinal bromoazides directly from olefin using N,N-dibromo-p-toluenesulfonamide (TsNBr₂) without any catalyst. The reaction is extremely fast which goes into completion instantaneously to produce bromoazides. This procedure is applicable to various olefins such as cinnamates, chalcone, styrenes, and acrylate to give the corresponding 1,2-bromoazide in an excellent yield.