Tetrahydropyrane derivatives

Positive halogen reagents can cyclize y- and 8-hydroxyalkenes to tetrahydro-furan and tetrahydropyran derivatives, respectively.85 Iodocyclization of homoal-lylic alcohols generates 3-iodotetrahydrofiirans when conducted in anhydrous acetonitrile.86 The reactions are stereospecific, with the /(-alcohols generating the irons and the Z-isomer the cis product. These are endo-5 cyclizations, which are preferred to exo-4 reactions. 

Recently, a new multicomponent condensation strategy for the stereocontrolled synthesis of polysubstituted tetrahydropyran derivatives was re-published by the Marko group, employing an ene reaction combined with an intramolecular Sakurai cyclization (IMSC) (Scheme 1.14) [14]. The initial step is an Et2AlCl-promoted ene reaction between allylsilane 1-50 and an aldehyde to afford the (Z)-homoallylic alcohol 1-51, with good control of the geometry of the double bond. Subsequent Lewis acid-media ted condensation of 1-51 with another equivalent of an aldehyde provided the polysubstituted exo-methylene tetrahydropyran 1-53 stereoselectively and... 

Die Tetrahydropyran-Derivate CXV bis CXVIII findet man in den oberirdischen Teilen verschiedener Dahlia-Arten (54). 

The required 1-oxa-l,3-diene precursor was synthesized according to the synthesis design (Scheme 8). Cycloadditon with enol ether furnished exclusively the endo-isomer. Raney nickel treatment in refluxing ethanol yielded in one step the desired tetrahydropyran derivative in a favorable 6 1 cis/trans ratio. Transformation into the lactone and ring closure with potassium tert.-butoxide afforded (+)-ramulosin. 

Electrophilic iodine reagents have also been employed in iodocyclization. Several salts of pyridine complexes with I+ such as bis(pyiidinium)iodonium tetrafluoroborate and bis(collidine)iodonium hexafluorophosphate have proven especially effective.61 y-Hydroxy- and d-hydroxyalkcncs can be cyclized to tetrahydrofuran and tetrahydropyran derivatives, respectively, by positive halogen reagents.62 (see entries 6 and 8 in Scheme... 

The key intermediate 14, a stable tetrasubstituted tetrahydropyran derivative, was obtained from commercially available methyl o-glucopyranoside 12 via a three-step reaction sequence (Scheme 4). First the primary hydroxyl group was protected as thexyldimethylsilyl (TDS) ether, then the other OH groups were methylated under standard conditions to give 13. The latter glycoside was deoxy-genated at the anomeric position by treatment at room temperature with a Lewis acid (trimethylsilyl triflate) and a hydride donor (triethylsilane). This treatment also... 

Unsaturated tetrahydropyran derivatives have received only cursory attention in the literature as heterocyclic monomers. 2,3-Dihydropyran and several of its substituted derivatives apparently undergo cationic polymerization in a manner typical of vinyl ethers (72MI11103), while tetrahydropyranyl esters of methacrylic acid (123) are fairly typical free radically polymerizable monomers (Scheme 35) (74MI11105). The THP group was used in this study as a protecting group for the acid functionality, and it was found that deprotection of polymers (124) could be accomplished under extremely mild conditions. 

The nature of C4H70+ ions derived from various tetrahydropyran derivatives has been investigated (81T781). 

Piperidine derivatives and acyclic substances such as trihalogeno-alkanes and dihalogenoalkylamines may be used as starting materials. The piperidine derivatives are obtained mainly from pyridine compounds. Dihalogenoalkylamines and trihalogenoalkanes are prepared from tetrahydropyran derivatives, dialkoxy-substituted malonic esters, or alkane-tetracarboxylic esters. 

Simple allenes (209) react with dimethyldioxirane (200) to give the corresponding spiro-dioxides 210 in instances where diastereoisomeric spiro-dioxides are possible, there is usually an acceptable stereochemical preference for epoxidation to occur anti to the alkyl substituents324,325. Allenic alcohol 211 yields the highly functionalized tetrahydro-furan 212 and tetrahydropyran derivatives by intramolecular nucleophilic addition of the hydroxy group to an intermediate allene diepoxide324. 

Intramolecular examples of iron-catalyzed formal Alder-ene reactions, which are also denoted cycloisomerization reactions, were described in the late 1980s by the groups of Tietze and Takacs in reactions directed towards cyclopentane [6, 7], cyclohexane [8], piperidine [9] and tetrahydropyran derivatives [10]. 

In summary, the SMS reaction is a truly efficient process, possessing a broad scope and applicable to a number of carbonyls, allylsilanes, alcohols (silyl ethers) or amines. Its usefulness has been validated in several total syntheses and demonstrated by the preparation of chiral homoallylic alcohols. During the development of the SMS reaction, Melkafia and Marko [48] realized that the homoallylic alcohol (ether), if connected to an allylsilane, would form novel annelating agents that would lead to tetrahydropyran derivatives via condensation with carbonyl compounds. This reaction was called IMSC for intramolecular Sakurai cydization and will be discussed in the next section. 

Epoxides undergo cross-cyclization with homoallylic alcohols in the presence of zirconium tetrachloride under mild conditions to give the corresponding tetrahydropyran derivatives (Scheme 45).75... 

A ceric ammonium nitrate (CAN) mediated stereoselective cyclization of epoxypropyl cinnamyl ethers 352 provides a facile route to 3,4,5-trisubstituted tetrahydropyran derivatives 353 (Equation 149) <2004TL2413>. 

A large scale synthesis of a chiral tetrahydropyran derivative (five steps, 56% overall yield) from (+)-10-camphor-sulfonic acid has been described the sulfide is of value in the asymmetric synthesis of epoxides and aziridines <2006T11297>. 

Comparison of Eq. (1) derived from the r(C-OR) versus pKz (ROH) plot for the anri-periplanar P-trimethylsilyl esters 98-102 with Eq. (3) derived for the 2-substituted tetrahydropyran derivatives 117 reveals a similar response of the C-OR bond distance to the electron demand of the OR substituent. This is consistent with the similar energies (and hence donor abilities) of a C-Si bond and an oxygen lone-pair orbital (Tables 1 and 2). Thus the above structural data suggest that the oc Si-Oj- o interaction in 98-102 is similar in magnitude to the n0-Oc o present in 117. Also consistent with the present interpretation is the plot of C-OR distance versus pKd (ROH) for structures derived from the gauche P-trimethylsilyl alcohol 118,97... 

Simple tetrahydropyran derivatives in syntheses of natural products 91MI60. 

The most common use of tetrahydropyran derivatives is as protecting groups you met this in Chapter 24 and you can see an example later in the chapter, on p. 1132. 

This modification resulted in a yield improvement for the pentacyclization process from 47 % to 66 %. Treatment of the amino ether 192 with diisobutylaluminum hydride in refluxing toluene accomplished Eschenmoser-Grob fragmentation and reduction of the initially formed immonium ion, to give the unsaturated amino alcohol 193 in 86% yield. It was gratifying to find that 193 was the only product formed in this reaction. In the tetrahydropyran derivative, reduction of 192 to 193 is accompanied by about 15 % simple elimination. Displacement of the tosyl group in 196 gives sulfide 197, which is oxidized to sulfone 198. This material is metallated and coupled with enantiomerically pure aldehyde to secure the codaphniphylline skelton [74]. 

The and A -unsaturated acids [62, 63] and unsaturated alcohols [62] yield tetra-hydrofuran-2-one or tetrahydropyran-2-one and tetrahydrofuran or tetrahydropyran derivatives, respectively, when electrolyzed in MeOH or CH2CI2 containing PhSeSePh and NH4Br or Et4NBr. Examples of products and respective precursors are shown in Eqs. (28) and (29). 

Pyranose derivatives adopt chair conformations unless an unusual combination of destabilizing interactions is present. Angyal developed a set of destabilizing interactions that can be used to estimate the relative stabilities of the two chair conformers in aqueous solution [125,126]. These values were determined before many of the A-values discussed above for cyclohexane and tetrahydropyran derivatives were measured and are formulated in terms of 1,3-diaxial... 

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