Synthesis and stereochemistry of 1-alkyl-2-aryl-3-(2-methyl-2,3-epoxypropionyl) aziridines

Two diastereoisomeric 1-alkyl-2-aryl-3-(2-methyl-2,3-epoxypropionyl) aziridines with an E configuration of the aziridine ring were obtained by the reaction of 2-methyl-2-cinnamoyoxiranes with iodine-methylamine and iodine-ethylamine complexes. The relative configuration of the chiral centers of the synthesized compounds was established by means of spectral data. The predominant formation of diastereomers with the RRR (SSS) relative configuration is explained by the effect of steric factors in the diastereomeric chelated amino enols that precede the formation of the epoxy keto aziridines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 880–883, July, 1980.     

Selective ring-opening of nonactivated amino aziridines by thiols and unusual nucleophilic substitution of a dibenzylamino group

[Reaction: see text]. The reaction of chiral 2-(1-aminoalkyl)aziridines 1 with different thiols, in the presence of BF3*Et2O, is reported. The obtained products were dependent on the structure of the starting amino aziridines 1. Thus, enantiopure (2S,3S)-2-(alkylthio)alkane-1,3-diamines 2 were obtained from aziridines with C-2 substituents with lower steric congestion and partially racemized (2S,3S)-2,3-bis(alkylthio)alkan-1-amines 3 (ee = 56-66%) from aziridines with larger C-2 subtituents. In both cases, the opening of the nonactivated aziridine ring at C-2 took place with retention of configuration and proceeded with regio- and stereoselectivity at C-2. In the synthesis of 3, 2 equiv of thiol reacts with 1 and the opening of aziridine ring at C-2 was followed by an unusual displacement of the dibenzylamino group by a second equivalent of thiol. The regiochemistry and relative configuration of compounds 3 was established by single-crystal X-ray analysis. A mechanism is proposed to explain the results obtained.     

Heteroatomic derivatives of aziridine. 15. Reaction of 1-(triethylsilyl)- and 1-[2-(trialkylsilyl)ethyl]-aziridines with thiols

The reaction of 1-(triethylsilyl)aziridine with alkanethiols proceeds with splitting out of aziridine and the formation of (alkylthio)triethylsilanes. The reaction of 1-(triethylsilyl)aziridine with 2-mercaptoethanol leads to 2-(triethylsilyloxy)ethanethiol; the same reaction in a closed system leads to [2-(2-aminoethylthiol)ethoxy]triethylsilane. 1-[2-(Trialkylsilyl)ethyl]aziridines react with 2-mercaptoethanol and with mercapto carboyxlic acids with opening of the aziridine ring.See [1] for Communication 14.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 891–893, July, 1988.     

Efficient Regioselective Ring Opening of Activated Aziridine-2-Carboxylates with [18F]Fluoride

Aziridines can undergo a range of ring-opening reactions with nucleophiles. The regio- and stereochemistry of the products depend on the substituents on the aziridine. Aziridine ring-opening reactions have rarely been used in radiosynthesis. Herein we report the ring opening of activated aziridine-2-carboxylates with [¹⁸F]fluoride. The aziridine was activated for nucleophilic attack by substitution of various groups on the aziridine nitrogen atom. Fluorine-18 radiolabelling was followed by ester hydrolysis and removal of the activation group. Totally regioselective ring opening and subsequent deprotection was achieved with tert-butyloxycarbonyl- and carboxybenzyl-activated aziridines to give α-[¹⁸F]fluoro-β-alanine in good radiochemical yield.     

Reactivity of allenoates toward aziridines: [3+2] and formal [3+2] cycloadditions

The reactivity of buta-2,3-dienoates toward aziridines is reported. Allenoates react as 2π-component in the [3+2] cycloaddition with the azomethine ylide generated from cis-1-benzyl-2-benzoyl-3-phenylaziridine affording 4-methylenepyrrolidines in a site-, regio-, and stereoselective fashion. Under conventional thermolysis, cis- and trans-2-benzoyl-1-cyclohexyl-3-phenylaziridines showed a different reactivity. These aziridines participate in formal [3+2] cycloadditions with allenes via C-N bond cleavage of the three-membered ring leading to functionalized pyrroles.     

Synthesis,stereochemistry, and isomeric transformations of 4-aryl-5-aroyl-2-methylthio-2-imidazolines

The corresponding 4-aryl-5-aroyl-2-methylthio-2-imidazolines were obtained by the reaction of complexes of cis- and trans-3-aroylaziridines and boron trifluoride with methyl thiocyanate. It is shown on the basis of spectral data that the aziridine ring is opened regiospecifically at the C(₂) atom and stereospecifically with inversion of the configuration.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1484–1488, November, 1988.     

Transformation of trans-4-aryl-3-chloro-1-(2-chloroethyl)azetidin-2-ones into 3-aryl-2-(ethylamino)propan-1-ols via intermediate 1-(1-aryl-2-chloro-3-hydroxypropyl)aziridines and trans-2-aryl-3-(hydroxymethyl)aziridines

trans-4-Aryl-3-chloro-1-(2-chloroethyl)azetidin-2-ones, prepared through cyclocondensation of chloroketene and the appropriate imines in a diastereoselective way, were unexpectedly transformed into 3-aryl-2-(ethylamino)propan-1-ols using LiAlH(4) in THF under reflux. A stepwise analysis showed that the initially formed 1-(1-aryl-2-chloro-3-hydroxypropyl)aziridines were converted into trans-2-aryl-3-(hydroxymethyl)aziridines, most probably via N-spiro bis-aziridinium intermediates, which were subsequently prone to undergo ring opening by LiAlH(4) to afford 3-aryl-2-(ethylamino)propan-1-ols.     

Development of a [3+3] cycloaddition strategy toward functionalized piperidines

This paper describes a novel route to functionalized piperidines via a formal [3+3] cycloaddition reaction of activated aziridines and palladium-trimethylenemethane (Pd-TMM) complexes. The cycloaddition reaction generally proceeds enantiospecifically with ring opening at the least hindered site of the aziridine. Therefore, readily available enantiomerically pure 2-substituted aziridines can be utilized to prepare enantiomerically pure 2-substituted piperidines in good to excellent yield. The N-substituent on the aziridine proved to be crucial to the success of this reaction with only 4-toluenesulfonyl (Ts) and 4-methoxybenzenesulfonyl (PMBS) aziridines permitting smooth cycloaddition to take place. Additionally, spirocyclic aziridines have been found to participate in the [3+3] cycloaddition reaction, whereas 2,3-disubstituted aziridines can be applied to provide fused bicyclic piperidines, albeit in low yield.     

非对称氮杂环丙烷的亲核开环反应及其区域选择性

本文系统地总结了各类亲核试剂对非对称氮杂环丙烷(吖丙啶)的亲核开环反应及开环的区域选择性.氮杂环丙烷亲核开环的区域选择性是一种空间效应和电子效应平衡的结果,非芳基和非烯基取代的氮杂环丙烷的亲核开环通常发生在氮杂环丙烷取代少的碳原子上,空间效应起主导作用;而芳基和烯基取代的氮杂环丙烷的亲核开环通常发生在氮杂环丙烷芳甲位和烯丙位的碳原子上,电子效应起主导作用,烯基取代的氮杂环丙烷的亲核开环还可以发生在烯基的β-碳原子上;分子内的亲核开环反应主要受成环时环大小的控制,成环时的倾向是五元环>六元环>七元环.对于亲核试剂,一般的亲核试剂也同时受电子效应和空间效应的影响; 而亲核性强的亲核试剂通常只受空间效应的影响.容易生成稳定自由基的亲核试剂容易发生单电子转移机理的开环反应,生成相当于亲核试剂进攻氮杂环丙烷中取代多的碳原子得到的开环产物.     

Reactivity of N-(omega-haloalkyl)-beta-lactams with regard to lithium aluminium hydride: novel synthesis of 1-(1-aryl-3-hydroxypropyl)aziridines and 3-aryl-3-(N-propylamino)propan-1-ols

The reactivity of 4-aryl-1-(2-chloroethyl)azetidin-2-ones and 4-aryl-1-(3-bromopropyl)azetidin-2-ones with regard to lithium aluminium hydride has been evaluated for the first time. 4-Aryl-1-(2-chloroethyl)azetidin-2-ones were transformed into novel 1-(1-aryl-3-hydroxypropyl)aziridines through an unprecedented conversion of beta-lactams into 2,3-unsubstituted aziridine derivatives. Unexpectedly, 4-aryl-1-(3-bromopropyl)azetidin-2-ones underwent dehalogenation towards 3-aryl-3-(N-propylamino)propan-1-ols upon treatment with LiAlH(4). 1-(1-Aryl-3-hydroxypropyl)aziridines were further elaborated by means of ring opening reactions using benzyl bromide in acetonitrile towards 3-aryl-3-[N-benzyl-N-(2-bromoethyl)amino]propan-1-ols and using aluminium(iii) chloride in diethyl ether, affording 3-aryl-3-[N-(2-chloroethyl)amino]propan-1-ols.     

Stereochemistry and bonding in N-substituted-2-phenyl-3-cyanoaziridines

A series of ten N-alkyl(aralkyl)-2-phenyl-3-cyanoaziridines has been synthesized to continue investigations of the molecular stereochemistry and bonding of functionalized aziridines. Substantial spectroscopic evidence is presented which indicates the presence of stereoselective hyperconjugation between the phenyl and nitrile groups and the aziridine ring. The ¹H and ¹³C nmr chemical shifts are rationalized in terms of the interactions of the substituents on the aziridine ring, and how these interactions vary with the steric bulk of the nitrogen substituents. Various stereoselective coupling constants (¹H-¹H and ¹³C-¹H) are also reported.     

Reactivity of activated versus nonactivated 2-(bromomethyl)aziridines with respect to sodium methoxide: a combined computational and experimental study

The difference in reactivity between the activated 2-bromomethyl-1-tosylaziridine and the nonactivated 1-benzyl-2-(bromomethyl)aziridine with respect to sodium methoxide was analyzed by means of DFT calculations within the supermolecule approach, taking into account explicit solvent molecules. In addition, the reactivity of epibromohydrin with regard to sodium methoxide was assessed as well. The barriers for direct displacement of bromide by methoxide in methanol are comparable for all three heterocyclic species under study. However, ring opening was found to be only feasible for the epoxide and the activated aziridine, and not for the nonactivated aziridine. According to these computational analyses, the synthesis of chiral 2-substituted 1-tosylaziridines can take place with inversion (through ring opening/ring closure) or retention (through direct bromide displacement) of configuration upon treatment of the corresponding 2-(bromomethyl)aziridines with 1 equiv of a nucleophile, whereas chiral 2-substituted 1-benzylaziridines are selectively obtained with retention of configuration (via direct bromide displacement). Furthermore, the computational results showed that explicit accounting for solvent molecules is required to describe the free energy profile correctly. To verify the computational findings experimentally, chiral 1-benzyl-2-(bromomethyl)aziridines and 2-bromomethyl-1-tosylaziridines were treated with sodium methoxide in methanol. The presented work concerning the reactivity of 2-bromomethyl-1-tosylaziridine stands in contrast to the behavior of the corresponding 1-tosyl-2-(tosyloxymethyl)aziridine with respect to nucleophiles, which undergoes a clean ring-opening/ring-closure process with inversion of configuration at the asymmetric aziridine carbon atom.     

Synthesis of enantiopure imidazolines through a Ritter reaction of 2-(1-aminoalkyl)aziridines with nitriles

The Ritter reaction of enantiopure 2-(1-aminoalkyl)aziridines 1 with different nitriles afford enantiopure tetrasubstituted imidazolines 2. The opening of the aziridine ring takes place with total regio- and stereoselectivity. A mechanism to explain the described addition reaction is proposed. [reaction: see text]     

Opening of the four-membered ring in perfluorinated 1-alkyl-2-phenyl- and 1-aryl-1,2-dihydrocyclobutabenzenes in the system I<Subscript>2</Subscript>-SbF<Subscript>5</Subscript>

Reactions of perfluorinated 1-phenyl-, 1-(2-ethylphenyl)-, 1-(4-ethylphenyl)-, 1-methyl-2-phenyl-, and 1-ethyl-2-phenyl-1,2-dihydrocyclobutabenzenes with iodine in antimony pentafluoride at 130°C, followed by hydroysis of the reaction mixture, resulted in the formation of perfluorinated 2-methyl-, 2-ethyl-2′-methyl-, 4-ethyl-2′-methyl-, 2-ethyl-, and 2-propylbenzophenones via opening of the four-membered ring in the initial cyclobutabenzene at the C¹–C² bond. The presence of hydrogen fluoride facilitates the process and promotes profound transformations leading to anthracene derivatives.     

Relationship between the configurations of 2-phenyltetrahydrothiophenium 1-methylides and their rearrangement products

trans-2-Phenyltetrahydrothiophenium 1-methylide (trans-3), which is generated by fluoride ion-induced desilylation of trans-2-phenyl-1-[(trimethylsilyl)methyl]tetrahydrothiophenium salt (trans-2), gave a mixture of 1,4,5,10a-tetrahydro-3H-2-benzothiocine (4) ([2,3]sigmatropic rearrangement product) and 4-methylsulfanyl-1-phenyl-1-butene (5) (Hofmann elimination product). Ylide trans-3 cannot undergo [2,3]sigmatropic rearrangement because the ylide-carbon is too far from the phenyl group, and trans-3 would instead isomerize to cis-3. In this paper, we discuss the mechanism of the isomerization of trans-3 to cis-3.     

1-(Phenylethynyl)aziridine in reactions with amines

The reaction of 1-(phenylethynyl)aziridine with a primary or secondary amine gave 2-benzylimidazoline-2 or N-aminoethyl substituted phenylacetamidine via nucleophilic attack on the aziridine ring. The mechanism of aziridine ring opening by an amine was studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 600–603, May, 1989.     

二芳杂环基乙烯的合成及其光致变色反应研究

本文报道了2,3-双 (1,2-二甲基-3-吲哚基)-2-丁烯 (DF1),2,3-双 (1,4-二苯基-2-甲基-3-吡咯基)-2-丁烯 (DF2), 2,3-双(1-对甲苯基-4-苯基-2-甲基-3-吡咯基)-2-丁烯 (DF3), 2,3-双(1-对溴苯基-4-苯基-2-甲基-3-吡咯基)-2-丁烯 (DF4) 和2,3-双 (1-对甲氧苯基-5-苯基-2-甲基-3-吡咯基)-2-丁烯 (DF5) 的合成,以及它们的光致变色行为的研究。特别是DF1和DF5的光呈色和光消色过程进行了较为细致的研究。     

Aziridinyl ketones XVII. The hydrogenation of 2-phenyl-3-aroylaziridines to aziridinylcarbinols

The sodium borohydride reduction of both cis and trans-1-cyclohexyl-2-phenyl-3-aroylaziridines provides in each case the corresponding carbinol as a mixture of the two possible diastereoisomeric racemates, whereas reduction of these ketones with lithium aluminum hydride or with lithium diisopropylamide provides only the racemate resulting from attack on the carbonyl group from the least hindered side. Catalytic hydrogenation of a cis aziridinyl ketone cleaved the aziridine ring and provided an amino carbinol.     

Novel synthesis of 3,4-diaminobutanenitriles and 4-amino-2-butenenitriles from 2-(cyanomethyl)aziridines through intermediate aziridinium salts: an experimental and theoretical approach

1-Arylmethyl-2-(cyanomethyl)aziridines were transformed into 4-(N,N-bis(arylmethyl)amino)-3-(pyrrolidin-1-yl)butanenitriles and 4-(N,N-bis(arylmethyl)amino)-2-butenenitriles via 4-(N,N-bis(arylmethyl)amino)-3-bromobutanenitriles in high yields and purity. The key steps involve the unprecedented regiospecific ring opening of intermediate 2-(cyanomethyl)aziridinium salts by bromide and pyrrolidine in acetonitrile, exclusively at the substituted aziridine carbon atom. The results were rationalized on the basis of ab initio calculations.     

A novel entry toward 2-imino-1,3-thiazolidines and 2-imino-1,3-thiazolines by ring transformation of 2-(thiocyanomethyl)aziridines

A new, efficient, and straightforward synthesis of 3-arylmethyl-4-chloromethyl-2-imino-1,3-thiazolidines and 2-(N-acylimino)-3-arylmethyl-4-chloromethyl-1,3-thiazolidines has been developed by ring transformation of 1-arylmethyl-2-(thiocyanomethyl)aziridines upon treatment with a catalytic amount of titanium(IV) chloride in dichloromethane. The latter 2-(thiocyanomethyl)aziridines were prepared in high yields from 1-arylmethyl-2-(bromomethyl)aziridines by reaction with potassium thiocyanate in DMF. The 2-imino-1,3-thiazolidines and 2-(N-acylimino)-1,3-thiazolidines thus obtained can be easily interconverted, either by treatment with an acid chloride and a base in ether toward 2-(N-acylimino)thiazolidines or by treatment with potassium carbonate in methanol toward N-deprotected 2-iminothiazolidines. Dehydrohalogenation of 2-(N-acylimino)-3-arylmethyl-4-chloromethyl-1,3-thiazolidines by means of potassium tert-butoxide in DMSO afforded 2-(N-acylimino)-4-methyl-2,3-dihydro-1,3-thiazolines in good yields.