Tetrahydropyran basicity

In order to overcome the special problems posed by brevetoxin B s tetrahydropyran systems, the decision was made to develop and test regio- and stereoselective ring closures employing two types of substrates hydroxy epoxides and hydroxy a,/ -unsaturated esters. The basic concepts of these reactions are shown in Schemes 1 and 2, respectively. 

The instability of protonated oxetane has prevented the determination of p/sfa or gas-phase basicity values for oxetane itself, whereas these have been obtained for tetrahydrofuran and tetrahydropyran. 3,3-Dialkyl substitution, however, sufficiently reduces the reactivity that pKa values can be obtained. The p/sTa for 3,3-dimethyloxetane has been determined to be -2.56, which is less than that for tetrahydrofuran (-2.08) but more than that for tetrahydropyran (-2.79). Since the 3,3-dialkyl substitution markedly reduces the basicity of oxetane towards iodine, the p/sfa of the parent oxetane must be greater than these values (see equation 8) (71BSF4576,80JOC1166). 

The reaction of dihydropyran with water in the presence of a trace of mineral acid gives an equilibrium mixture of 2-hydroxytetrahydropyran and 5-hydroxypentanal. However, the products from the addition of alcohols to dihydropyrans are stable under basic conditions and can be isolated after destruction of the acid catalyst (47JA2246). A wide range of substituted tetrahydropyrans has been made in this way and the diastereoisomers separated by gas chromatography (68JOC3754). 

Certain cyclic ethers which will not homopolymerize will copolymerize with THF (25, 52). These cyclic ethers are stable five and six-membered ring compounds such as 2-methyltetrahydrofuran (2-MeTHF), and 1,4-dioxane (DOX). It is probable that 4-phenyl-l,3-dioxane (PhDOX), tetrahydropyran (THP), and 4-methyl-l,3-dioxolane (MDOL) which do not homopolymerize but which have been reported to copolymerize with BCMO (107, 108) would also copolymerize with THF. In the copolymerizations a correlation was again found between the basicity of the attacking ether and its reactivity with the cyclic oxonium ion. The... 

Homoallylic alcohols. Allylsamarium reagents prepared in tetrahydropyran are quite stable (in THF Wurtz coupling occurs, therefore the Barbier technique must be employed). The sequential procedure made possible by change of solvent gives cleaner products as side reactions such as pinacol formation from ketones and decarbonylation of acid chlorides are avoided. Because of the low basicity allylsamarium reagents can be used to allylate allyl acetoacetate. 

The formation of acetals, by the acid catalyzed addition of hydroxyl compounds to a,/8-ethylene ethers is a useful method of protecting the hydroxyl group in reactions effected in basic media.—E 3-Chloro-l-propanol and dihydropyran, with a few drops of coned. HC1, allowed to stand for 3 hrs. with occasional shaking —> 2-(y-chloropropoxy)-tetrahydropyran. Y 78%. (F. e. s. W. E. Parham, E. L. Anderson, Am. Soc. 70, 4187 (1948).)... 

The glycals react with water, alcohols, phenols, carboxylic acids, and certain bases, in the presence of an acidic catalyst, in the same way as does 2,3-dihydro-4/f-pyran (which gives, for example, 2-hydroxy-, 2-alkoxy-, and 2-aryloxy-tetrahydropyrans in high yield ). (Tetrahydro-pyranyl ethers are useful for protecting alcoholic groupings during reactions in basic media, and are readily hydrolyzed with acid,) The first step of these additions would be expected to be protonation at C-2, followed by attack of the nucleophilic reagent on the resonance-stabilized, C-1 carbonium ion. 

Copolymerization was carried out in C2H5C1 solvent at 0 °C and at 40 mol % total comonomer concentration with a A1(C2H5)3-H20 catalyst system 13). Under these conditions, depropagation of THF and tetrahydropyran (THP) should be taken into account, and thus r, and r2 derived from Scheme (15-1) cannot be equal for these monomers to the corresponding rate constant ratios (reactivity ratios). Therefore, only results for oxiranes and oxetanes can be discussed. It should be noted that in spite of the higher strain of the three-membered rings, their incorporation into the copolymer is slower than that of the more basic oxetanes. 

Nitroethanol was recently employed as C/O bis-nucleophile by Hayashi and coworkers [38] for the synthesis of optically active functionalized tetrahydropyrans by reaction with enals using diphenylprolinol silyl ether as the organocatalyst (Scheme 16.18). The diastereoselectivity of the Michael/acetalization sequence was improved by isomerization to the thermodynamically more stable trans isomers upon basic treatment. 

The spirostane structure is the basic skeleton of this class of plant constituents which occurs partly together with the cardiac glycosides. Additional isomers are possible here, depending on the a- or jS-position of the methyl group at 25 and the tetrahydropyran ring at... 

In addition to hydrogen halides, water is the most studied HBD in the gas phase. The structures of the complexes with water, dinitrogen, carbon monoxide, ozone, benzene, ethane, formaldehyde, formamide, 1,4-dioxane, ethylene oxide, tetrahydropyran, difluo-romethane, pyrazine, pyrimidine, pyridazine, benzonitrile, quinuclidine, ammonia, methy-lamine, trimethylamine and so on can be found in the Mogadoc database [29]. In the water-morpholine complex [30], water is hydrogen bonded to the nitrogen and not to the oxygen, as predicted by the higher HB basicity of amines than that of ethers. 

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