Tetrahydropyran , cyclic derivatives

As these acetals could be converted into the 4,6-O-ethylidene derivatives on treatment with acid, it was reasoned that use of a cyclic vinyl ether, namely, 3,4-dihydro-2H-pyran, might prevent this second process, thus leading to a more useful method of selective acetalation.338 An equimolar reaction with methyl a-D-glu-copyranoside for 4 days in N,N-dimethylformamide led to utilization of 88% of the glycoside, and the 6-(tetrahydropyran-2-yl) ether constituted —85% of the crude reaction-product. In contrast to the steric control apparent in this instance, reaction of 3,4-dihydro-2H-pyran with the axial and equatorial hydroxyl groups in dl-1,4,5,6-tetra-O-acetyl-mi/o-inositol was completely unselective,339 a fact that has been rationalized310 in terms of the probable mechanism of these reactions. 

There are very few precedents for the reaction of cyclic a-halo ethers with carbanions. Zelinski and coworkers114 and Schudel and Rice115 reported the preparation of diethyl DL-tetrahydropyran-2-ylmalonate (137) by treatment of 2-bromo- or 2-chloro-tetrahydropyran (136) with diethyl sodiomalonate. The product was subsequently converted into the malonic and acetic acid derivatives, 138 and 139, respectively. The same sequence has also been reported by other workers.116... 

Spirocyclic 4-substituted tetrahydropyrans are readily obtained through the Prins reaction involving cyclic ketones, homoallylic alcohols and MeS03H <02H(58)659>. The cationic species generated when alkyne-Co complexes derived from 8-valerolactone are treated with SnCl4 undergo a double cyclisation to yield the oxaspiro[5.5]undecane <02T2755>. 

Pyrans (Oxanes) The six-membered cyclic ethers are commonly named as derivatives of pyran, an unsaturated ether. The saturated compound has four more hydrogen atoms, so it is called tetrahydropyran (THP). The systematic term oxane is also used for a six-membered ring containing an oxygen atom. 

The ketone component can be replaced by cyclic enol ethers, which react with phenylhydrazines to give phenylhy-drazones, as has been demonstrated by a large-scale synthesis of 5-fluorohomotryptophol derivatives from 4-fluorophe-nylhydrazine hydrochloride and tetrahydropyran <19970PD300>. The Grandberg modification of the Fischer synthesis involves the use of an acetal as the ketone equivalent <2001T1041>. 

Lactols and their acetals can be transformed easily into their 2-arylsulfonyl derivatives 337 by reaction with a sulfinic acid under Lewis acid activation. The corresponding organolithiums are prepared by deprotonation with n-BuLi or LDA and, after reaction with electrophiles, a /(-elimination of sulfinic acid afforded a cyclic a-substituted enol ether514,547,548. 2-Lithio-2-(arylsulfonyl)tetrahydropyrans equilibrated to give mainly the anomer with the lithium atom at the equatorial position549. 

We reported the first examples of asymmetric catalysis of intramolecular carbonyl-ene reactions of types (3,4) and (2,4) using the BINOL-derived titanium complex (1) [80,83]. The catalytic 7-(2,4) carbonyl-ene cyclization gives the oxepane with high ee, and gem-dimethyl groups are not required (Sch. 27). In a similar catalytic 6-(3,4) ene cyclization, the fram-tetrahydropyran is preferentially produced, with high ee (Sch. 28). The sense of asymmetric induction is exactly the same as observed for the glyoxylate-ene reaction—the (f )-BINOL-Ti catalyst provides the (R)-cyclic alcohol. 

A different mechanism was adopted in the biosynthesis of cyclic polyethers such as monensin. These PK-derived polycycles are formed in a cascade fashion with other enzymatic transformations. For example, in the biosynthesis of monensin (Equation 8.2), the cascade polyether formation is triggered by epoxidation of a polyene template [40]. Similar mechanisms can probably be used to make other polyether antibiotics containing tetrahydrofurans and tetrahydropyrans [41]. 

From the methodological point of view, a different F factor derived from the correlation of energies of relevant acyclic compounds should have been used. The anomeric carbon atom in II is secondary, whereas in 2-substituted tetrahydropyrans it is tertiary. The introduction of a third substituent at the anomeric carbon may result in a change of preferred conformation (58, 59), appropriate angles (60), and the magnitude of the anomeric effect (61), thus making cyclic models inadequate for the calculation presented above. 

The reaction of polysaccharides ivith aldehydes to give cross-linked products has been known and exploited industrially for some time. Starch acetals may also be prepared by a method that does not give rise to cross-links and involves treatment of starch with a cyclic vinyl ether, 3,4-dihydro-2H-pyran, to give a tetrahydropyran-2-yl derivative (16). At low levels of substitution, the acetals are water-soluble, at... 

Cyclic PAF analogues, such as the chiral tetrahydropyrans 361 and 363, represent con-formationally restricted glycerol derivatives that exhibit potent PAF antagonistic activity [126]. A twelve-step sequence converts 349 or 353 to (2i ,3 S)-(360) (ee = 98.8%) or (2S,3R)-2-triphenylmethoxymethyltetrahydropyran-3-ol (362) ( = 96.8%), respectively. These are then appropriately transformed to the corresponding PAF products 361 and 363 [127]. 

X-ray analysis of some of the cyclic oligomers described above has been achieved so far. The cyclic dimer derived from the racemic monomer is composed of a pair of different enantiomeric units and all of the four substituents attached to the two tetrahydropyran rings are oriented axially [11]. Such a structure of the cyclic dimer is compatible with the fact that no cyclic dimer was produced from the optically active monomer. 

For keto-hexoses, however, the pyranose derivatives are not the major hemiketals that are formed. Cyclization via the OH unit at C5 will lead to furanose derivatives as the preferred structure. Why In Chapter 8, cyclopentane was lower in energy than cyclohexane, but the compounds here are cyclic ethers. Indeed, the tetrahydropyran ring is somewhat more stable than the tet-rahydrofuran ring. Stabilization of the hydroxyl groups and the hydroxymethyl... 

The catalytic method was extended to a series of different unsaturated alcohols in order to investigate the scope of the reaction. More specifically, only substrates leading upon protonation to the formation of tertiary carbocations turned out to be suitable substrates for the reaction. In all cases, the synthesis of a wide range of differently substituted tetrahydropyran and oxepane derivatives was achieved under mild experimental conditions within up to 6 days, with only 10 mol% of the supramolecular capsule as catalyst, while in the presence of the ammonium competitive guest the reactions were sluggish. For all substrates, the hydroalkoxylation always showed the formation of the cyclic product corresponding to the Markovnikov addition to the unsaturated double bond. 

As a first extension of the new overall enantioselective a-alkylation of 2-ke-toesters we developed an efficient asymmetric synthesis of 3-substituted cyclic hemiketals of (o-hydroxy-2-oxoesters [42]. As is depicted in scheme 15, the metalated SAMP-hydrazones were trapped with a number of O-benzyl- and O-silyl-protected co-hydroxy-l-iodoalkanes, which after hydrazone cleavage and deprotection afforded the cyclic hemiketals (de, ee > 98%), structurally modified deoxygenated analogs of ulosonic acids. To our knowledge only two methods have been reported for the synthesis of similar simple tetrahydropyran derivatives [43,44]. 

Intramolecular alkoxymetalation of alkenes is one of the efficient methods to prepare cyclic ethers. He and co workers have reported that silver (I) triflate catalyzes the intramolecular addition of alcohols to olefins [26]. The reaction of 2,2-diphenyl-4-hexen-l-ol (16) under the influence of 5 mol% of the silver(I) catalyst affords a 10 1 mixture of tetrahydrofuran derivative (17) and tetrahydropyran derivative (18) in high combined yield (Scheme 18.6). In the case of terminal disubstituted y-hydroxyl alkenes, 6-endo cyclization products are formed exclusively. This procedure has been successfully expanded to cyclization of pent-4-enoic acid, hex-5-enoic acid, and their derivatives leading to the corresponding lactones [26]. Using similar cyclization methods catalyzed by silver(I) compounds, 1-allenyl isochromenes [27], dihydrobenzofurans [28], and dihydrobenzopyrans [28] have been synthesized. 

Monosaccharides occur as substances with a free carbonyl group (acyclic compounds) and as cyclic hemiacetals, also called lac-tols. Trioses are exclusively acyclic substances, tetroses and higher monosaccharides exist predominantly in five- and six-membered and, exceptionally, also in seven-membered cyclic structures. They can therefore be regarded as substances derived from oxolane (tetrahydrofuran), oxane (tetrahydropyran) or oxepane, and are thus actually heterocyclic compounds. Acyclic forms, which exist in constitutional equilibrium with cyclic forms, occur in zigzag conformers, as well as alditols (see Section 4.3.1.1.1). 

As a fuel becomes larger and/or more functionalized, the properties and reaction pathways of the resulting radicals and peroxy radicals are likewise more varied. For instance, comparing the cyclic ether tetrahydropyran (THP) to its FIC analog cyclohexane (Figure 4), it is evident that three isomeric radicals are possible from the former, relative to only one in the latter moreover, each of these three TFIP-derived radicals can proceed to... 

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