Examination of homo-[3 + 2]-dipolar cycloaddition: mechanistic insight into regio- and diastereoselectivity

The reaction of 2,3-disubstituted-1,1-cyclopropanediesters with nitrones under Lewis acid conditions produces tetrahydro-1,2-oxazines in which the cis/trans relationship of the cyclopropanes is not conserved. Reacting nitrones with 2,3-cis-disubstituted cyclopropanes lead to 5,6-trans-oxazines, and 2,3-trans-disubstituted cyclopropanes lead to 5,6-cis-oxazines. This observed stereochemical inversion provides evidence for a stepwise annulation mechanism in the preparation of tetrahydro-1,2-oxazines.     

2-silyloxy-1,2-oxazines, a new type of acetals of conjugated nitroso alkenes

3-alkyl-substituted 1,2-oxazine N-oxides 2 can be selectively transformed into 2-silyloxy-1,2-oxazines 1 upon treatment with silylating reagents. In the solid state derivatives 1 adopt a chair conformation with the pyramidal nitrogen atom, whereas in solution they exist as an equilibrating mixture of two conformers (DeltaG++ 55-60 kJ/mol). A preliminary study of the reactivity of nitrosals 1 has shown that they react with O- and N-stabilized carbocations to yield 1,2-oxazine N-oxides with a functionalized alkyl substituent at the 3-position. Moreover, compounds 1 can rearrange into silyloxy-1,2-oxazines 5 and react with morpholine to produce 3-morpholinoalkyl-1,2-oxazines 7 existing in a tautameric equilibrium with open-chain oximes 6.     

Enantioselective addition of nitrones to activated cyclopropanes

In this paper, we demonstrate the first examples of chiral Lewis acid catalysis in the formation of tetrahydro-1,2-oxazines with very high enantioselectivity starting with diactivated cyclopropanes and nitrones (>90% yields and ee). Reactions with racemic substituted cyclopropanes provide approximately 1:1 diastereomeric tetrahydro-1,2-oxazine products with high enantioselectivity. Mechanistic information for the formation of the tetrahydro-1,2-oxazines is also detailed.     

Expedient synthesis of pyrrolo[1,2-a]indoles: preparation of the core of yuremamine

Pyrrolo[1,2- a]indoles are conveniently prepared from tetrahydro-1,2-oxazines, which in turn are generated through the reaction of nitrones with 1,1-cyclopropanediesters. The synthetic route proves to be highly diastereoselective and provides access to the core of the recently discovered pyrrolo[1,2- a]indole natural product yuremamine.     

A sequential enantioselective, organocatalytic route to chiral 1,2-oxazines and chiral pyridazines

A sequential, organocatalysed asymmetric reaction to access chiral 1,2-oxazines and chiral pyridazines is reported, which proceeds in moderate to good yields and good to excellent enantioselectivities.     

A highly selective, organocatalytic route to chiral 1,2-oxazines from ketones

A sequential, organocatalysed asymmetric reaction to access chiral 1,2-oxazines from achiral ketone starting materials is reported, which proceeds in moderate to good yields and excellent enantioselectivity.     

Hetero-Diels-Alder reaction of phosphinyl and phosphonyl nitroso alkenes with conjugated dienes: an aza-Cope rearrangement

Phosphorylated nitroso alkenes react with cyclic dienes such as cyclopentadiene or cyclohexadiene to afford hetero Diels-Alder-type cycloadducts where the nitroso alkene participates as dienophile component and the cyclic olefin acts as the 4π-electron (diene) system. Subsequent aza-Cope rearrangement affords highly functionalized 5,6-dihydro-4H-1,2-oxazines. Conversely, the reaction of TMS-substituted cyclopentadiene (dienophile) with nitroso alkenes as heterodienes leads directly to bicyclic 1,2-oxazines. Theoretical studies are in agreement with the experimental results and with the new aza-Cope rearrangement proposed.     

Nitrogen inversion in 3,6-dihydro-1,2-oxazines

The nitrogen inversion barriers of nine 3,6-dihydro-1,2-oxazines are discussed. Polar solvents were found to increase the nitrogen inversion barriers which, in turn, decrease with increasing size of the N-substituent.     

Synthesis of 6-hydroxymethyl-5,6-dihydro-4H-1,2-oxazines by one-pot-cyclization of dilithiated oximes with epibromohydrin

6-Hydroxymethyl-5,6-dihydro-4H-1,2-oxazines were regioselectively prepared by one-pot cyclization of dilithiated oximes with epibromohydrin.     

Rearrangement of 3-alkylidene-2-siloxy-tetrahydro-1,2-oxazines (ASENA). A new approach toward the synthesis of 3-α-hydroxyalkyl-5,6-dihydro-4H-1,2-oxazines

A new approach toward the synthesis of 3-α-hydroxyalkyl-5,6-dihydro-4H-1,2-oxazines 1 from available 5,6-dihydro-4H-1,2-oxazine N-oxides 2 has been described. The key step of the process—the rearrangement of 3-alkiliden-2-siloxy-tetrahydro-1,2-oxazines 3 (ASENA)—was thoroughly investigated. Optimal experimental conditions were developed. A possible pathway of the ASENA rearrangement was proposed.     

Synthesis of 1,2- and 1,4-amino alcohols from 1,3-dienes via oxazines. Rearrangements of 1,4-amino alcohol derivatives to oxazolines

Conjugated dienes were converted to 1,2-oxazines by reaction with an acyl nitroso dienophile. The oxazines were reduced to 1,4-N-acetylamino alcohols, which were rearranged to the corresponding oxazolines upon treatment with methanesulfonyl chloride or anhydride. The oxazolines yielded 1,2-N-acetylamino alcohols upon hydrolysis. Thus either 1,4- or 1,2-N-acetylamino alcohols are available from 1,3-dienes via this methodology. Experimental and spectral data are provided for all new compounds.     

Domino reactions of 1,2-diimidoyl-1,2-dichloroethanes. Synthesis of 3-imino-1,2-dithia-3h-cyclopent-4-enes, 3-amino-2-thioxo-2,5H-pyrrol-5-ones, 2,3-diamino-4-thioxo-4H-thiopyrans, and 6-imino-6H-1,3-oxazines

The reaction of mono- and dilithiated ethyl thioglycolate with 1,2-diimidoyl-1,2-dichloroethanes, aza-analogues of oxalyl chloride, afforded (depending on the reaction conditions) 3-imino-1,2-dithia-3H-cyclopent-4-enes, 3-amino-2-thioxo-2,5H-pyrrol-5-ones, and 2,3-diamino-4-thioxo-4H-thiopyrans. The reaction of the dianion of ethyl hippurate with 1,2-diimidoyl-1,2-dichloroethanes afforded 6-imino-6H-1,3-oxazines.     

Regioselective synthesis of 6-halomethyl-5,6-dihydro-4H-1,2-oxazines based on cyclizations of arylalkenyl-oximes

6-Iodo- and 6-bromomethyl-5,6-dihydro-4H-1,2-oxazines were prepared by condensation of dilithiated acetophenone-oximes with allylbromide and subsequent regioselective iodine- or NBS-mediated cyclization.     

Heterocyclen aus α-nitroolefinen. XI . 1,2-oxazine aus α-nitroolefinen und β-dicarbonylverbindungen

Dihydro-1,2-oxazines 8 and 12-oxazines 12 are formed by the reaction of the nitronic acids of the adducts of α-nitroolefins and β-dicarbonyl compounds ( 6 ) by two ways: A ) The nitronic acids 6 are heated in a boiling solution of urea in ethanol or methanol. B ) The nitronic acids 6 are reduced with an aqueous solution of ammoniachloride and sodium sulfide. ¹H-nmr and ¹³C-nmr investigations prove the constitutions. The mechanism is discussed.     

One-pot cyclizations of dilithiated oximes and hydrazones with epibromohydrin. Efficient synthesis of 6-hydroxymethyl-5,6-dihydro-4H-1,2-oxazines and oxazolo[3,4-b]pyridazin-7-ones

The one-pot cyclization of dilithiated oximes with epibromohydrin provided a convenient and regioselective approach to 6-hydroxymethyl-5,6-dihydro-4H-1,2-oxazines. The reaction of the latter with phosphorus tribromide resulted in a Beckmann rearrangement and formation of 5-bromomethyl-2-iminotetrahydrofurans. The reaction of dilithiated hydrazones with epibromohydrin afforded oxazolo[3,4-b]pyridazin-7-ones, which were formed by a novel domino cyclization.     

Retro-ene reactions in heterocyclic synthesis,III. A new route to 4,5-dihydrooxazoles and 5,6-dihydro-4H-1,3-oxazines

Methyl (E)-4,4-dimethyl-5-oxo-2-pentenoate ( 1 , X = O) reacted with 1,2- or 1,3-aminoalcohols 3 to yield oxazolidines 4a-c or tetrahydro-1,3-oxazines 4d,e. The corresponding imino ester 1 (X = NBu-t) also gave 4 on reaction with 3 . Compounds 4 on heating at 230° yielded 4,5-dihydrooxazoles 5a-c or 5,6-dihydro-4H-1,3-oxazines 5d,e along with methyl 4-methyl-3-pentenoate ( 6 ).     

A highly selective, organocatalytic route to chiral dihydro-1,2-oxazines

[reaction: see text] The organocatalyzed asymmetric synthesis of chiral dihydro-1,2-oxazines from achiral starting materials proceeds in moderate to excellent yields and excellent enantioselectivity. This sequential reaction gives the desired products in a single pot.     

Synthesis of derivatives of dihydro-1,2-oxazine and tetrahydro-1,2-diazine from (4-chlorobutanoyl)-alkoxybenzenes

The reaction of (4-chlorobutanoyl)alkoxybenzenes with hydroxylamine and 2,4-dinitrophenylhydrazine gave dihydro-1,2-oxazines and tetrahydro-1,2-diazines, respectively.Institute of Petrochemical Processes, Academy of Sciences of the Republic of Azerbaijan, 370025 Baku. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 7, pp. 1685–1687, July, 1992.     

1,2-oxazine chemistry—I : Synthetic approaches to tetrahydro-1,2-oxazines

The synthesis of a series of N-carbethoxytetrahydro-1,2-oxazines, by the reaction of 1,4-dibromobutane derivatives with N-hydroxyurethane under basic conditions, and their reduction to N-Me derivatives is described. Stereochemical and mechanistic points of interest in these reactions are discussed.     

A new ring transformation: Synthesis of 5,5-dimethyl-3-oxo-1-pyrroline 1-oxides from 6,6-dimethyl-4-oxo-5,6-dihydro-1,2,4h-oxazines

The nitrosation of some γ,δ-unsaturated β-diketo compounds affords the 3-substituted 4-oxo-5,6-dihydro-1,2,4H-oxazines. These compounds are converted to the isomeric 3-oxo-1-pyrroline 1-oxides by a facile thermal rearrangement.