Substituted aziridines by lithiation-electrophile trapping of terminal aziridines

[reaction: see text] Regio- and stereoselective deprotonation of N-Bus (Bus = tert-butylsulfonyl)-protected terminal aziridines with lithium 2,2,6,6-tetramethylpiperidide generates a nonstabilized (H-substituted) aziridinyl anion that undergoes in situ or external electrophile trapping under experimentally straightforward conditions to give trans-disubstituted aziridines in good to excellent yields.     

Lewis acid-promoted carbon-carbon bond cleavage of aziridines: divergent cycloaddition pathways of the derived ylides

Lewis acids are shown to cleave the carbon-carbon bond of activated aziridines at ambient temperature. The derived metal-coordinated azomethine ylides undergo cycloaddition reactions with electron-rich alkenes. Cyclic alkenes afford products that are formally [4+2] adducts most likely derived from a Mannich-type addition to the ylide, followed by intramolecular Friedel-Crafts alkylation. Alternatively, acyclic alkenes undergo [3+2] cycloaddition to give new pyrrolidine products.     

Intramolecular cyclopropanation of unsaturated terminal aziridines

[STRUCTURE: SEE TEXT] Regio- and stereoselective deprotonation of bishomoallylic terminal N-Bus (Bus=tert-butylsulfonyl)-protected aziridines generate aziridinyl anions that undergo diastereoselective intramolecular cyclopropanation giving trans-2-aminobicyclo[3.1.0]hexanes in good to excellent yields.     

Electrophilic intramolecular cyclization of functional derivatives of unsaturated compounds: VI. Reaction of 2-(cyclohex-2-en-1-yl)acetanilides with arylsulfanyl chlorides. Structural and quantum chemical study of isomerization of 2-(2-arylsulfanyl-3-chlorocyclohexyl)acetanilides

2-(Cyclohex-2-en-1-yl)acetanilides react with arylsulfanyl chlorides in chloroform to give 2-(2-arylsulfanyl-3-chlorocyclohexyl)acetanilides which undergo isomerization into 2-chloro-3-arylsulfanylsubstituted derivatives in polar solvents. According to the results of quantum chemical calculations, the addition of arylsulfanyl chlorides to 2-(cyclohex-2-en-1-yl)acetanilides is characterized by negative Gibbs energy. Specific conformation of the isomerization products is stabilized by weak (non-covalent) interactions which make them more energetically favorable than the initial compounds. The reactions of 2-(cyclohex-2-en-1-yl)acetanilides with arylsulfanyl chlorides in nitromethane in the presence of lithium perchlorate lead to the formation of mixtures of the corresponding addition products and electrophilic intramolecular cyclization products, N-[7-(arylsulfanyl)octahydro-1-benzofuran-2-ylidene]anilinium perchlorates, which are converted into free bases by treatment with sodium ethoxide.     

Rhodium-catalyzed stereoselective formation of Z-enamines from allylaziridines

Rhodium (I)-catalyzed isomerization of N-allylaziridines affords isolable Z-enamines in excellent yields and with high stereoselectivity. Cationic [Rh(BINAP)(COD)]OTf and RhH(CO)(PPh3)3 follow the same selectivity toward the Z-isomers. This selectivity is not observed with other N-allylamines which give the thermodynamically more stable E-isomers. These unexpected results suggest a possible deviation from the commonly accepted mechanism of isomerization. Preliminary results show that the Z-enamines undergo cycloaddition with DMAD to form highly strained N-cyclobutenyl aziridines.     

2,3,7‐Triazabicyclo[3.3.0]octenes Prepared by Tandem Cascade Reaction of Allyl Azides and Olefinic Dipolarophiles

Tandem cascade reactions of allylazides and olefinic dipolarophiles to give cis‐fused 2,3,7‐triazabicyclo [3.3.0]octenes ( 5, 6 or 7 ) are reported. Therein, an intermolecular dipolar cycloaddition of azide and alkene gave a triazoline which was followed by isomerization of the triazoline to a diazoester ( 4 ) and then an intramolecular dipolar cycloaddition from the diazo functional group and the double bond in 4 to give 5 . Compound 5 may further more undergo a Michael addition to give 7‐substituted‐ 2,3,7‐ triazabicyclo [3.3.0]oct‐2‐ene ( 6 ) or a tautomerization to give 2,3,7‐triazabicyclo[3.3.0]oct‐3‐ene ( 7 ). The reaction may be manipulated to stop at a particular stage by adopting a suit able solvent or an appropriate temperature.     

Competitive isomerization and dimerization in co-crystals of 1,1,6,6-tetraphenyl-2,4-hexadiyne-1,6-diol and sorbic acid: a new look at stereochemical requirements for [2+2] dimerization

Competitive [2+2] photodimerization and E-->Z isomerization reactions occur in a co-crystal of 1,1,6,6-tetraphenyl-2,4-hexadiyne-1,6-diol upon irradiation with 325 nm light. At 90 K both reactions are observed, whereas at 280 K the dimerization reaction is very fast and inhibits isomerization as the nature of the chromophore is affected by the reaction. The temperature dependence of the stereospecificity of the dimerization reaction is related to the large sliding motion required to bring the reacting molecules into juxtaposition. The progress of the reactions has been monitored by photocrystallographic methods.     

An efficient approach to azirino and pyrrolo-fused dibenzazepines. Conformations of substituted dibenzo[c,f]pyrrolo[1,2-a]azepines

An effective approach to azepino-fused heterocycles is described. trans-1-Aryl-7,11b-dihydro-1H-azirino[1,2-a]dibenzo[c,f]azepines were synthesised via a domino sequence: isomerization of gem-dichloroaziridine-intramolecular Friedel-Crafts acylation of the tethered benzene ring catalysed by SnCl(4) and subsequent hydride induced intramolecular cyclization. Cycloaddition of dibenzazepinium ylides, generated by heating these aziridines, to activated C[double bond]C, C[triple bond]C dipolarophiles and fullerene C(60), leads to derivatives of dibenzo[c,f]pyrrolo[1,2-a]azepine. The reaction proceeds with complete stereoselectivity via cycloaddition of only W-ylide, which due to the high barrier does not undergo E,Z-isomerization under the reaction conditions. It was found that 2,3,9,13b-tetrahydro-1H-dibenzo[c,f]pyrrolo[1,2-a]azepine systems can exist in conformations of two types depending on the substituents at the pyrrolidine carbons in β-position with respect to nitrogen. Details of cycloaddition reactions and the conformational behavior of cycloadducts were studied by DFT calculations at the B3LYP/6-31G(d) level.     

Aza-pinacol rearrangement: acid-catalyzed rearrangement of aziridines to imines

A series of di-, tri-, and tetra-substituted N-tosylaziridines [N-(toluene-p-sulfonyl)aziridines] 1, prepared by aziridination of the corresponding alkenes with N-[(tolyl-p-sulfonyl)imino]phenyliodinane (TsN = IPh), was found to undergo a BF3-catalyzed rearrangement (aza-pinacol rearrangement) under mild conditions to give the corresponding N-tosylimines 2 generally in satisfactory yields.     

Intramolecular PhI=O mediated copper-catalyzed aziridination of unsaturated sulfamates: a new direct access to polysubstituted amines from simple homoallylic alcohols

[reaction: see text] Olefinic sulfamates derived from primary and secondary alcohols undergo intramolecular copper-catalyzed aziridination in the presence of iodosylbenzene to afford novel bicyclic fused aziridines. The latter were opened by various nucleophiles to give the corresponding substituted cyclic sulfamates, which in turn reacted, after nitrogen activation, with a second nucleophile at the carbon atom bearing the oxygen atom. Concomitant removal of the sulfonyloxy moiety thus gave access to polysubstituted amines.     

REACTIONS OF THIOPHENES AND ACETYLENES IN POLAR AND APOLAR SOLVENTS

Abstract

Although the aromatic 6π-electron system of thiophenes is rather unreactive in cycloaddition reactions we have found that several thiophene derivatives react with acetylenes. Alkylthiophenes undergo (2+2)-cycloaddition reactions with electron-deficient acetylenes in apolar solvents in the presence of Lewis acids to give 2-thia-bicyclo [3. 2. 0] hept-3, 6-dienes (1). These compounds show isomerization via an a, a-Cope rearrangement at temperatures of 100 to 150°C.     

Synthesis of stable isoxazolines by [3+2] cycloaddition of oxaziridines with alkynes

N-Alkyl substituted oxaziridines undergo a [3+2] cycloaddition reaction with a variety of terminal alkynes to give the product isoxazolines, whose stability appears to depend on the electronic properties of the groups on the C-3 and C-5 positions. The presence of an electron withdrawing group on C-5 and/or an electron donating group on C-3 causes isomerization of the isoxazolines to β-amino enones.     

Asymmetric synthesis of 2H-azirine 3-carboxylates

[reaction: see text] Dehydrochlorination of methyl 2-chloroaziridine 2-carboxylates generates the first examples of enantiopure 2-substituted 2H-azirine 3-carboxylates which undergo the aza Diels-Alder reaction with dienes to give bicyclic and tricyclic aziridines in good yields.     

Preparation and reactions of 3-oxa- and 4-oxa-5-hexenyllithiums

Low-temperature lithium–iodine exchange between tert-butyllithium and the appropriate iodide has been used to generate 3-oxa-5-hexenyllithium and a variety of 4-oxa-5-hexenyllithiums. The 3-oxa system is inherently unstable and fragments via facile β-elimination to give the anion of allyl alcohol and ethylene. The 4-oxa-5-hexenyllithiums, in contrast, are stable at low temperatures but undergo novel isomerization upon warming to deliver the lithium salt of a 4-alken-1-ol in the formal equivalent of an unprecedented [1,4]-Wittig rearrangement. The rearrangement is most likely mediated by 5-exo-trig ring closure of the 4-oxa-5-hexenyllithium to a (2-tetrahydrofuranyl)methyllithium followed by rapid opening to the alkoxide.     

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.     

Aziridines from intramolecular alkene aziridination of sulfamates: reactivity toward carbon nucleophiles. application to the synthesis of spisulosine and its fluoro analogue

Catalytic intramolecular alkene aziridination of sulfamate is an emerging methodology for the asymmetric synthesis of chiral functionalized amines involving the formation of bicyclic aziridines. This study demonstrates the ability of the latter to undergo ring-opening with various carbon nucleophiles: Grignard reagents, lithium salts of terminal alkynes, dithiane, malonate. These S(N)2-type reactions occur with high levels of regio- and chemoselectivity to generally afford seven-membered cyclic sulfamidates in good yields. Carbon nucleophiles have also been found to react with these sulfamidates provided that the sulfamate ester has been previously activated by introduction of a tosyl substituent on the NH group. The versatility of this strategy has been illustrated with the syntheses of spisulosine and its fluoro analogue.     

Reactions of aziridines. Preparation and properties of 2-thiazolinium salts

Reaction of 1-substituted aziridines with thioamides in the presence of perchloric acid has provided a facile route to 2-thiazolinium salts. Thioformamide was used in this reaction to give the 2-unsubstituted 2-thiazolinium salts 3-[4-(2,6-xylyloxy)butyl]-2-thiazolinium perchlorate (11a) and 3-(2-cyelohexylbutyl)-2-thiazolinium perchlorate (IIc). A study of the rates of hydro-lytic breakdown of IIc and 3-(2-cyelohexylbutyl)-2-methyl-2-thiazolinium perchlorate (IId) showed that the 2-unsubstituted compound (IIc) was considerably less stable than the 2-methyl analog (IId) over the entire pH range. Use of 1-substituted aziridines in ring-opening reactions, previously applied only to 1-unsubstituted aziridines, has given expected products when thio-cyanate ion or thiourea was the nucleophile.     

2-Ene-1,4-diols by dimerization of terminal epoxides using hindered lithium amides

[reaction: see text] Reaction of hindered lithium amides with readily available (enantiopure) terminal epoxides gives 2-ene-1,4-diols via carbenoid dimerization of the corresponding alpha-lithiated epoxides. D-Mannitol and D-iditol were synthesized using this method in three steps from (S)-tritylglycidyl ether.     

Prototropic Isomerization of Spiro[2,3]hexanes 1,1,5-Trisubstituted with Electron-acceptor Groups into 1,3-Disubstituted Bicyclo[1.1.0]butanes

1,1-Dicyano- and 1,1-dialkoxycarbonylspiro[2.3]hexane-1-carbonitriles treated with lithium diisopropylamide or potassium tert-butylate in THF undergo a prototropic isomerization into 3-(2,2-dicyanoethyl)- and 3-(2,2-dialkoxycarbonylethyl)bicyclo[1.1.0]butane-1-carbonitriles respectively.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 2, 2005, pp. 201–204.Original Russian Text Copyright © 2005 by Razin, Ulin.     

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.