Application of peptidyl radicals into a new radical cascade leading to unsaturated gamma-lactams

Radical cyclization of dipeptides 1a-h proceeds smoothly to give five- and seven-membered rings in good to moderate total yields using Stork's catalytic tin hydride method. A radical is generated on a protecting group and translocated to the peptide moiety. Following a cyclization reaction, the vinyl radical can abstract hydrogen from a benzyl group on an amine, which results in elimination of the protected amine group. Encouraging results have notably been obtained with amino acids other than glycine.     

Reaction of chlorosulfonyl isocyanate with aziridines

The reaction of chlorosulfonyl isocyanate (CSI) with 1,2,3-triphenylaziridine (1) and some cis- and trans-1-cyclohexyl-2-aroyl-3-phenylaziridines, 4-7 and 19-22 has been described. The cis-isomers of aziridines, 4-7 , undergo a smooth reaction with CSI to give the corresponding cis-isomers of 2-chlorosulfonylimino-1,3-oxazolidines, 8-11 , in good yields (65-67%). While the trans-isomers, 19-22 , gave unusual products 23-26 which have been assigned a bicyclic structure, based on their physical and spectral (ir, pmr, ms) data. Plausible mechanisms have been postulated to explain the transformations.     

Reaction of aziridines with acetylenic γ-hydroxy aldehydes

The corresponding acetylenic aziridino hydroxy carbinols were obtained by the reaction of aziridine, 2,2-dimethylaziridine, and methyl aziridine-2-carboxylate with 4-hydroxy-4-methylpent-2-yn-1-al and 3-(1-hydroxycyclohexyl)prop-2-yn-1-al. It is shown that the latter at room temperature undergo isomerization with time to 2-hydroxy-4-aziridino-5,5-dialkylduiydrofurans. The isomerization of acetylenic aziridinocarbinols, which includes an intermediate step involving retrodecomposition of the aziridino (hydroxy) carbinols to the starting aldehydes and aziridines, was investigated by dynamic NMR spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 334–337, March, 1979.     

Reaction of oxiranes with lithium: deoxygenation leading to olefins

Mono-, di-, tri- and tetra-substituted epoxides undergo facile deoxygenation yielding olefins when treated with lithium in tetrahydrofuran. Aliphatic epoxides yield olefins with the same stereochemistry as the parent compound.     

Reaction mechanism of the alternating copolymerization of aziridines with cyclic imides

The copolymerizations of N-substituted aziridines and cyclic imide were studied. N-Ethylsuccinimide copolymerized with ethylenimine, but N-ethylethylenimine did not copolymerize with succinimide and N-ethylsuccinimide without catalyst. The effect of additives on the copolymerization of ethylenimine with succinimide and that of N-ethylethylenimine with succinimide and N-ethylsuccinimide was also examined. The rate of copolymerization of ethylenimine with succinimide was accelerated by the addition of N-acetylethylenimine or water. The copolymerization of N-ethylethylenimine with succinimide was initiated only by water, but N-ethylethylenimine did not copolymerize with N-ethylsuccinimide in the presence of water. Gas evolved on heating the copolymer of ethylenimine and succinimide was analyzed and confirmed to be ammonia. On the basis of these results the reaction mechanisms of the copolymerization of ethylenimine with succinimide or N-ethylsuccinimide and of N-ethylethylenimine with succinimide initiated by water are discussed.     

Heteroatomic derivatives of aziridine. 12. Reaction of 1-(carbomethoxyalkyl)aziridines with thiols and mercapto acids

The reaction of 1-(carbomethoxyalkyl)aziridines with thiols and mercapto acids, which leads to the formation of the corresponding sulfides and esters of S-substituted N-(2-mercaptoethyl)amino acids, was studied. The acid hydrolysis of o-[(N-carbomethoxyethyl)-2-aminoethylthio]benzoic acid and o-[(N-cyanoethyl)-2-aminoethylthio]benzoic acid leads to o-[N-(carboxyethyl)-2-aminoethylthio]benzoic acid hydrochloride. The cyclization of 1-[(N-carbomethoxyethyl)-2-aminoethylthio]benzoic acid in the presence of PCl₃ gives 5-oxo-4-(carbomethoxyethyl)-6,7-benzoperhydro-1,4-thiazepine.See [1] for communication 11.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 921–923, July, 1981.     

Investigation of a flexible enantiospecific approach to aziridines

A flexible approach to functionalized and enantioenriched aziridines has been developed from an intermediate aziridinylmethyl tosylate. This protocol features a Cu-catalyzed Grignard substitution reaction that allows a range of functionalized organic fragments to be incorporated. Moreover, a convenient one-pot procedure is outlined that allows the trityl group to be exchanged for a range of common N-protecting groups.     

Carbonylative ring expansion of aziridines to beta-lactams with rhodium-complexed dendrimers on a resin

Rhodium-complexed dendrimers, supported on a resin, were evaluated as catalysts for the carbonylative ring expansion reactions of a variety of aziridines with carbon monoxide to give beta-lactams. The effects of reaction temperature, solvent, time, and pressure of carbon monoxide on this transformation were also investigated. The dendritic catalysts showed comparable activity to the homogeneous analogue. More importantly, this catalytic system can be easily recovered by simple filtration and recycled without significant loss of activity.     

Addition reactions of iodomethyllithium to imines. A direct and efficient synthesis of aziridines and enantiopure amino aziridines

An efficient and general synthesis of aziridines by the reaction of imines derived from p-toluenesulfonamides with in situ generated iodomethyllithium, with a simple and rapid experimental protocol, is reported for the first time. The reaction with the chiral aldimine derived from phenylalaninal allowed access to (2R,1'S)-2-(1'-aminoalkyl)aziridine with very high diastereoselectivity, in enantiopure form. A mechanism to explain this novel reaction is proposed.     

Organophosphorus chemistry,XII. Reaction of furil with alkyl phosphites and ylide-phosphoranes

Summary The reaction of furil (1) with trialkyl phosphites2 yielded caged phosphorane derivatives of types3a-c. Dry hydrogen chloride gas converted3a-c into the respectivea-hydroxyvinyl-phosphates8a-c which are equally produced by reacting furil with the appropriate dialkyl phosphite7. The reaction of furil with ylide-phosphoranes10 proceeded according to the Wittig reaction mechanism to give the respective ethylenes11a-c. The new compounds have been characterized by their spectroscopic data (IR, PMR,³¹P-NMR, MS) and elementary analyses.Dedicated to Prof. M. Sidky on the occasion of his 60th birthday     

Reaction pathways leading to arylene ethynylene macrocycles via alkyne metathesis

Mechanistic studies on the direct formation of arylene ethynylene macrocycles via alkyne metathesis catalyzed by a molybdenum complex are reported. Gel permeation chromatography (GPC) and matrix-assisted laser desorption ionization (MALDI) mass spectrometry on the products from metathesis of monomer 1 show the initial formation of linear oligomers and large macrocycles (n > 6), followed by their transformation into the thermodynamically most stable product distribution-mainly the cyclic hexamer. Variable temperature and scrambling experiments reveal the reversibility of macrocycle formation. Nearly identical product distributions are observed from the cross metathesis of hexacycle 2 with diphenylacetylene and from the metathesis of bis(phenylethynyl) substituted monomer 4, demonstrating that macrocycle formation is thermodynamically rather than kinetically controlled. The metathesis byproduct, 3-hexyne, is shown to inhibit the catalyst. It is suggested that the relative metathesis rates of dialkylalkynes versus diarylalkynes trap the catalyst in a nonproductive manifold, rendering it unavailable for the productive metathesis of aryl alkylalkyne substrates. This finding indicates that dialkyl-substituted alkyne byproducts should be avoided (or efficiently removed) if the metatheses of aryl substrates, especially those with electron-withdrawing groups, are to proceed to high conversion.     

Reactions with aziridines XXI The (Michaelis-)arbusov reaction with N-acyl aziridines and other amidoethylations at phosphorus.

Heating trialkyl phosphites with N-acyl aziridines produces dialkyl 2-amidoethyl-phosphonates bearing one of the phosphite alkyl groups on nitrogen. Other alkoxy phosphines behave analogously. Dialkyl phosphites furnish the same type of products devoid of the N-alkyl group.     

Reaction of alkynylsilanes with CuCl in polar solvents leading to alkynyl group transfer from Si to Cu

The reaction of 1-phenyl-2-trimethylsilylethyne with CuCl at 80–100°C in N,N-dimethylformamide (DMF) or N,N-dimethylimidazolidinone (DMI) yielded the alkynylcopper species [Cu₂Cl(CCPh)]_n (1) in 56–63% yields. Heating 1 at 80°C under aerobic conditions gave 1,4-diphenyl-1,3-butadiyne in 82% yield via an oxidative coupling of the phenylethynyl ligands.     

Diastereoselective synthesis of gamma-lactams by a one-pot, four-component reaction

A new one-pot, four-component reaction (4CR) between amines, maleic anhydrides, aldehydes, and thiols has been discovered to form tetra- and pentasubstituted gamma-lactams with high diastereoselectivity. Each component is independently variable and employed in equivalent stoichiometry, producing only water as a byproduct.