2- tetrahydropyrans

Six-membered Rings.- Tetrahydropyrans. Oxidative cyclization of the hydroxy-silanes (66) can be accomplished by treatment with iodosylbenzene and a Lewis acid affording the tetrahydropyrans (67) in moderate yield (38-68%).  

The polyether natural products have provided an excellent testing ground for oxygen heterocyclic synthesis, and have also inspired many new methods. Nicolaou s group has shown that in contrast to the usual mode of cyclization onto an epoxide, the 

Further studies on the hetero-Diels-Alder reaction by Danishefsky s group have focused on the stereochemistry of the reaction and the exact mechanism involved. Thus cyclization of dienes with aldehydes in the presence of BF. Et20 tends to give 

CH2CI2) push the mechanism toward a stepwise siloxonlum aldol-type cycladditlon, The use of ZnCl2 in THF, on the other hand, is 

The hetero-Diels-Alder reaction of 1-methoxybutadiene with aldehydes normally requires high pressures ( 15 kbar), and the use of Lewis acid catalysts such as ZnCl2 and BF. Et20 causes polymerization of the diene. However, by using the mild Lewis acids such as 

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Diiodobutane and 1 5 diiodopentane are eonveniently obtained from tetrahydrofuran and tetrahydropyran respectively (compare corresponding bromides above). 

Some allenic alcohols can be prepared in analogous waysfrom acetylenic epoxides or tetrahydropyrans ... 

In MeOH, l,4-dimethoxy-2-cyclohexene (379) is obtainejl from 1,3-cydo-hexadiene[315]. Acetoxylation and the intramolecular alkoxylation took place in the synthesis of the naturally occurring tetrahydrofuran derivative 380 and is another example of the selective introduction of different nucleo-philes[316]. In intramolecular 1,4-oxyacetoxylation to form the fused tetrahy-drofurans and tetrahydropyrans 381, cis addition takes place in the presence of a catalytic amount of LiCI, whereas the trans product is obtained in its absence[317]. The stereocontrolled oxaspirocyclization proceeds to afford the Irons product 382 in the presence of Li2C03 and the cis product in the presence of LiCl[ 318,319]. 

Typical carbon-oxygen bond distances m ethers are similar to those of alcohols (—142 pm) and are shorter than carbon-carbon bond distances m alkanes (—153 pm) An ether oxygen affects the conformation of a molecule m much the same way that a CH2 unit does The most stable conformation of diethyl ether is the all staggered anti conformation Tetrahydropyran is most stable m the chair conformation—a fact that has an important bearing on the structures of many carbohydrates... 

In the NTC region, back-bitiag reactioas appear to be respoasible for the formation of cycHc ethers (60,165—170). la additioa to oxetanes and tetrahydrofurans, tetrahydropyrans, oxiranes, and others are also observed (60,96,169) the tetrahydrofurans are favored. 0-Heterocycle yields of 25 to 30% have been reported for / -pentane (165,171). Conjugate and other olefins are also prominent products ia this regioa (60,169—172). 

Alkoxyall l All l Peroxides. / /f-Butyl tetrahydropyran-2-yl peroxide [28627 6-5] (1), where R = tert — butyl, X = OR", R = H, R and R" = 1, 4 butanediyl, has been isolated. This is one of many examples of alkoxyalkyl alkyl peroxides which may be prepared by reaction of hydroperoxides with vinyl ethers (139) ... 

The ether oxygen of tetrahydropyran (45 X = O) induces a large downfield shift of the a carbons, while the /3 and y carbons move slightly upfield, the y more noticeably. 

Two interesting syntheses of the base followed in 1956 the first involves a Principal Synthesis from ethyl 2-cyano-2-(tetrahydropyran-2 -yloxy)acetate and guanidine to give the tetrahydropyranyloxypyrimrdine (949) which undergoes gentle acidic hydrolysis to... 

Methanol, l-isoquinolyl(phenyl)-confonnation, 2, 110 Methanol, pyrimidinyl-synthesis, 3, 113 Methanol, tetrahydropyran-2-yl-microwave spectra, 3, 625 Methantheline as neurotransmitter, 1, 175 therapeutic properties, 3, 882 Methaphenilene biological activity, 4, 911 Methapyrilene biological activity, 4, 911 toxicity, 4, 912 Methaqualone, 3, 150 as anticonvulsant, 1, 166 pyrido[2,3-d]pyrimidine analogues metabolism, 3, 205 as sedative, 1, 166 Metharbitone as anticonvulsant, 1, 166 Methazolamide... 

THF, Et3NHCe(ni) (N03)6, 50-100°, 8 h, 30-98% yield. Hindered alcohols give the lower yields. The method was also used to introduce the THP group with tetrahydropyran. 

Table 3.8. Comparison of Conformational Free-Energy Values for Substituents on Tetrahydropyran, 1,3-Dioxane, and 1,3-Dithiane Rings with Those for Cyclohexane...

The incorporation of heteroatoms can result in stereoelectronic effects that have a pronounced effect on conformation and, ultimately, on reactivity. It is known from numerous examples in carbohydrate chemistry that pyranose sugars substituted with an electron-withdrawing group such as halogen or alkoxy at C-1 are often more stable when the substituent has an axial, rather than an equatorial, orientation. This tendency is not limited to carbohydrates but carries over to simpler ring systems such as 2-substituted tetrahydropyrans. The phenomenon is known as the anomeric ect, because it involves a substituent at the anomeric position in carbohydrate pyranose rings. Scheme 3.1 lists... 

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