Hydroxyl-functionalized cyclic ethers

The reaction processes shown in Scheme 8 not only accomplish the construction of an oxepane system but also furnish a valuable keto function. The realization that this function could, in an appropriate setting, be used to achieve the annulation of the second oxepane ring led to the development of a new strategy for the synthesis of cyclic ethers the reductive cyclization of hydroxy ketones (see Schemes 9 and 10).23 The development of this strategy was inspired by the elegant work of Olah 24 the scenario depicted in Scheme 9 captures its key features. It was anticipated that activation of the Lewis-basic keto function in 43 with a Lewis acid, perhaps trimethylsilyl triflate, would induce nucleophilic attack by the proximal hydroxyl group to give an intermediate of the type 44. 

The addition, therefore, follows Markovnikov s rule. Primary alcohols give better results than secondary, and tertiary alcohols are very inactive. This is a convenient method for the preparation of tertiary ethers by the use of a suitable alkene such as Me2C=CH2. Alcohols add intramolecularly to alkenes to generate cyclic ethers, often bearing a hydroxyl unit as well. This addition can be promoted by a palladium catalyst, with migration of the double bond in the final product. Rhenium compounds also facilitate this cyclization reaction to form functionalized tetrahydrofurans. 

Related catalytic enantioselective processes It is worthy of note that the powerful Ti-catalyzed asymmetric epoxidation procedure of Sharpless [27] is often used in the preparation of optically pure acyclic allylic alcohols through the catalytic kinetic resolution of easily accessible racemic mixtures [28]. When the catalytic epoxidation is applied to cyclic allylic substrates, reaction rates are retarded and lower levels of enantioselectivity are observed. Ru-catalyzed asymmetric hydrogenation has been employed by Noyori to effect the resolution of five- and six-membered allylic carbinols [29] in this instance, as with the Ti-catalyzed procedure, the presence of an unprotected hydroxyl function is required. Perhaps the most efficient general procedure for the enantioselective synthesis of this class of cyclic allylic ethers is that recently developed by Trost and co-workers, involving Pd-catalyzed asymmetric additions of alkoxides to allylic esters [30]. 

This group of compounds includes those monomers with one or more carbon atoms carrying a hydroperoxy or peroxy group, and also singly bonded to an oxygen atom present as hydroxyl, ether or cyclic ether functions. While the group of compounds is, in general, moderately stable, the lower 1-hydroxy and 1,T-dihydroxy-alkyl peroxides or hydroperoxides are explosive. Individually indexed compounds are ... 

Where several cyclic ethers can be formed by intramolecular tosyl te ion displacement, epoxide formation usually occurs In j>ref r ence to formation of larger other rings. This is particularly true whi-u the alternatives axe four- or six-memberecL There are often formed, however, tive-membeted oxides by attack of the C( hydroxyl un. 1 2,3-anhydro function,842-l 7 -1818 according to tho general scheme depicted in Eq- (252). Prolonged exposure of 2,3-anhydro sugars containing free hydroxyl functions at Ctn> to alkaline conditions > obviously undesirable for tliis reason. 

Given the presence of stable protecting groups on the hydroxyl functions of cyclic carbohydrate derivatives, photobrominations occur at the ether ring positions with facilities which depend upon the relative rates of hydrogen abstractions from the available sites67 (see Scheme 16). These, in turn,... 

Fluoride-induced -elimination of p-(trimethylsily )ethyl ethers, which is the cornerstone of the 2-(trtmethylsilyl)ethoxymethyl (SEM) protecting group for hydroxyl functions (see section 4.4.5), has been modified for use in deprotecting cyclic acetals. For example, 4-(trimethylsilyl)methyM,3-dioxolanes46 and 5-tri-methylsilyl-13-dioxanes47 cleave on heating with lithium tetrafluoroborate [Scheme 2.16], The method works well for unhindered aldehydes and ketones. 

Reaction of the aldehyde, Na-methylvellosimine (168), with 37% aqueous formaldehyde (25 equiv.) and 2 N KOH (10 equiv.) in methanol at room temperature for 10 h afforded optimum yields of the desired diol 211. The two prochiral hydroxymethyl functions in 211 were differentiated by the DDQ-mediated oxidative cyclization of the hydroxyl group at the 3-axial position of C-17 with the benzylic position at C-6. This gave the desired cyclic ether 212. Oxidation of the hydroxymethyl functionality was achieved with (PhSe0)20 to provide the aldehyde, which was further oxidized with KOH/R/MeOH to the methyl ester 210. Consequently, the total synthesis of (-l-)-dehydrovoachalotine (210) was achieved in 28% overall yield from D-(- -)-tryptophan. 

The variety of structural features exhibited by the selected allylo y and vinylojy monomers can be assessed from Scheme 7 linear structures with different chain lengths (allq l allyl ethers) or ojygenated cyclic structures (derivatives of solketal or glycerol carbonate, whose structure is close to a carbohydrate backbone, as well as pentosides) with or without hydroxylic functions in order to evaluate their influence on reactivity in donor-acceptor copolymerization. 

Ricinoleic acid contains a hydroxyl function at a stereogenic carbon atom. Such additional functional groups may interact with transition-metal catalysts causing directing effects or lead to their deactivation. In the hydroformylation of ethyl ricinoleate, the formed aldehydes are converted immediately into cyclic ethers by acetalization and subsequent dehydration (Scheme 6.87) [36]. 

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