The Addition of Nitrones to Olefins. Fused Bicyclic Isoxazolidines

Abstract

The oxidation of N-methyl-N-5-hexenylhydroxylamine with mercuric oxide and the condensation between 5-hexenal and N-methylhydroxylamine afforded cis-S-methyl-3-oxa-2-azabicyclo[3.3.0~octane (2). Other bicyclic isoxazolidines have been synthesized by the condensation reaction employing unsaturated aldehydes and unsaturated ketones. The structures of these compounds were proved by hydrogenolysis and, in some cases, independent synthesis of the amino alcohols. The mechanism of the cyclization reactions are postulated as intramolecular 1,3-additions of an unsaturated nitrone intermediate. The scope of this preparative route t o fused bicyclic isoxazolidines is discussed in terms of reactivity, orientation, and stereochemistry.The pyrolysis of a mixture of the isomeric N-methyl- methyl-8-oxa-2-azabicyclo[3.3.Oloctane (Z), and wasa-pipecoline oxides produced, in addition to the pre-postulated as having arisen from an unsaturated dicted unsaturated hydroxylamine, an unexpected nitrone intermediate (1). The nitrone may have been bicyclic base. * This product was identified as Nproduced from N-inethyl-N-5-hexenylhydroxylan1ine( 1 ) A preliminary communication concerning a part of this work has ap-by an oxidation-reduction reaction. However, this peared-J A m Chem Sot, 81, 6334 (1959). This work was reported in unsaturated hydroxylamine was obtained in good p a r t : Abstracts, 137th National Meeting of the American Chemical Society.Cleveland, Ohio, April 1960, p. 8.5-0.( 2 ) A C Cope and N A LeRel, J A m Chrm S o c , 81, 4656 (I$lRO)

First Total Synthesis of the Sex Pheromone of the Oleander ScaleAspidiotus nerii: An Unusual Sesquiterpenic Functionalized Cyclobutane

“…Preparation of (Z)-hept-5-enenitrile (7) was performed by three different reaction sequences: a) Wittig reaction of the phosphonium salt of 5-bromovaleronitrile with acetaldehyde in toluene and tBuOK as base in 60 % yield, [35] b) alkylation of 1-bromo-3-chloropropane with lithium acetylide followed by methylation of the terminal acetylene, cyanation and reduction to the cis nitrile 7 (24 % overall yield, 4 steps), [36] and c) nucleophilic substitution of the mesylate of (Z)-hex-4-enol (6) with sodium cyanide (83 % yield). Because of the simplicity and overall yield, this latter route was preferred for large-scale preparation of nitrile 7 (Scheme 2).…”

Intramolecular Cycloaddition Reactions of ω-Unsaturated Chiral Nitrones

“…of 97% (Scheme 3). LeBel et al reported that 1,3-dipolar cycloaddition of related 5-alkenyl-substituted nitrones yielded only cis-fused isoxazolidines [9] . Normally, diastereomeric mixtures of bicyclic com- pecially when present at the β-position, can induce the formation of only one of the possible diastereomers [10] [11] .…”

A versatile kinetic alkylation-ozonolysis route for the synthesis of lactones: chiral γ-lactones and racemic δ-lactones

“…Periodate oxidation followed by thermolysis in the presence of calcium carbonate gave 3-methyl-1,5-hexadien-3-ol, which on treatment with potassium hydride and 18-crown-6 gave the unsaturated ketone 5 in an overall yield of 60%. The ketone was also prepared using a modification of a previously published method 20 which involved the selective C-alkylation of ethyl acetoacetate with 4-iodobut-1-ene followed by dealkoxycarbonylation. The overall yield in this case was 44%.…”