Ethers, vinyl, reaction with amino-alcohols

Radical cyclizations are often used in ring formations and are an effective methodology in the synthesis of piperidines. The intramolecular cyclization of an oxime ether, such as 63 onto an aldehyde or ketone gives a new entry into cyclic amino alcohols <99JOC2003, 99H(51)2711>. Similarly, reaction of a terminal acetylene with BujSnH generates a vinyl radical, which will cyclize with an imine moiety to give 3-methylenepiperidine <99TL1515>. The indolizidine alkaloid ipalbidine was prepared by a sulfur-controlled 6-exo-selective radical cyclization of an a/p/ia-phenylthio amide <99H(50)31>. 

A diastereoselective formal addition of a 7ra i-2-(phenylthio)vmyl moiety to a-hydroxyhydrazones through a radical pathway is shown in Scheme 2.29. To overcome the lack of a viable intermolecular vinyl radical addition to C=N double bonds, not to mention a reaction proceeding with stereocontrol, this procedure employs a temporary silicon tether, which is used to hold the alkyne unit in place so that the vinyl radical addition could proceed intramolecularly. Thus, intermolecular addition of PhS" to the alkyne moiety in the chiral alkyne 161 leads to vinyl radical 163, which cyclizes in a 5-exo fashion, according to the Beckwith-Houk predictions, to give aminyl radical 164 with an a 7z-arrangement between the ether and the amino group. Radical reduction and removal of the silicon tether without prior isolation of the end product of the radical cyclization cascade, 165, yields the a-amino alcohol 162. This strategy, which could also be applied to the diastereoselective synthesis of polyhydroxylated amines (not shown), can be considered as synthetic equivalent of an acetaldehyde Mannich reaction with acyclic stereocontrol. 

The interest in functionalized ionic liquids is growing because ionic liquids bearing ether, amino or alcohol functionalities have been shown to display special properties, including the ability to dissolve a larger amoimt of metal halide salts and to extract heavy metal ions from aqueous solutions. Imidazolium-based ionic liquids with ether and hydroxyl (see Section 2.2.1), thiourea, thioether and urea (see Section 2.2.8) " have been prepared following the standard quatemization procedure. A straightforward approach has been described for the preparation of imidazolium (as well as pyridinium) cations with ester, ketone or cyanide functionalities 1-methylimidazole reacts with methanesulfonic acid to provide the imidazolium salt 11, which undergoes a Michael-type reaction with methyl vinyl ketone as a ,j8-unsaturated compound to produce the ionic liquid 12 (Scheme 5). ... 

As a special case, the formation of hemiacetals 2 (lactolization) during the hydroformylation of hydroxy-functionalized olefins, such as allyl or homoallyl alcohols, has to be mentioned (1, Y= O, Scheme 5.70). With these substrates, the reaction occurs in an intramolecular manner. In the presence of an external alcohol, the cyclic hemiacetal can further react to give a nonsymmetric cyclic acetal 3. Hemiacetals can be subjected to hydrogenation to afford diols 4. Under reducing conditions and in the presence of amines, amino alcohols 5 are formed both are valuable building blocks in fine chemistry. Alternatively, oxidation gives lactones 6 [5]. By dehydration of hemiacetals, cychc vinyl ethers 7 are formed. The same transformation with allylamines (Y=NR) gives cyclic hemiaminals, A/ ,0-acetals, lactames, or vinyl amines. 

Ozonolysis of the olefin followed by the reaction with lithium vinyl cuprate reagent produced 1,3-amino alcohol derivative 107 in 1 3 diastereomeric ratio. Protection of the compound 107 as tert-butyldimethylsilyl (TBS) ether, followed by treatment with a Pd catalyst and PhBr in a carboa-mination reaction condition, produced cyclic pyrrolidine derivative 109, which after subsequent reduction of the Boc group with LiAlH4 and deprotection of TBS ether was transformed into (-l-)-preussin 100 in 12% overall yield and 96% enantiomeric excess. 

Unsubstituted and Heat Reactive. The first class, the unsubstituted, heat-reactive resins, are made by using phenol, cresols, and xylenols. They are multifunctional and thus can be cross-linked to form films. They are soluble in alcohols, ketones, esters, and glycol ethers and insoluble in aromatic and aliphatic hydrocarbons. They will tolerate some water in their solvents and, in some cases, are completely water soluble. They are compatible with polar resins such as amino resins, epoxies, polyamides, and poly(vinyl butyral), though compatibility on curing is dependent on reaction between the two resins. Less polar resins such as alkyds and drying oils are incompatible. 

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