Tetrahydropyranal ether

A catalytic method which promises to find wide application in view of its mildness and ease of execution uses a catalytic amount of tetra-n-propylammonium perruthenate (TPAP) with A7-methylmorpholine -oxide (NMO) as the cooxidant. ° l4imary (and secondary) alcohols which contain a range of ftinc-tional groups (alkenes, tetrahydropyran ethers, epoxides, lactones, silyl ethers and indoles inter alia) can be oxidized without interference by the other functional group (equations 21-23). The performance of the reagent is improved further by including molecular sieves in the reaction mixture. ... 

The first chemically amplified resist was designed by G.H. Smith and J. A. Bonham of the 3M Company for which they were granted a U.S. patent in 1973. It was used in the acid-catalyzed deprotection of tetrahydropyranal ether from a polymer of tetrahydropyranal ether of novolac to generate a base-soluble phenol (novolac), as shown in Scheme 7.27. Incidentally, this work was never published in the open literature and was never exploited by 3M, and remained lost in the patent literature for a considerable length of time. 

Scheme 7.27 The chemically amplified resist system invented by G.H. Smith and J.A. Bonham of 3M. The photogenereated acid cleaves the lipophilic tetrahydropyranal ether to generate the base soluble phenol.

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. 

The outcomes of intramolecular cyclizations of hydroxy vinylepoxides in more complicated systems can be difficult to predict. In a study of the synthesis of the JKLM ring fragment of dguatoxin, epoxide 44 was prepared and subjected to acid-mediated cydization conditions (Scheme 9.24) [114]. Somewhat surprisingly, the expected oxepane 45 was not formed, but instead a mixture of tetrahydropyran 46 and tetrahydrofuran 47 was obtained, both compounds products of attack of the C6 and C5 benzyl ether oxygens, respectively, on the allylic oxirane position (C3). Repetition of the reaction with dimsylpotassium gave a low yield of the desired 45 along with considerable amounts of tetrahydropyran 48. 

As a strategy for the construction of cyclic ethers, the radical cyclization of jS-alkoxyacrylates was used for the preparation of czs-2,5-disubstituted tetrahy-drofurans and cis-2,6-disubstituted tetrahydropyrans. An example is given with S-alkoxymethacrylate 38 as precursor of the optically active benzyl ether of (+)-methyl nonactate, exclusively formed as the threo product (Reaction 44). ° ... 

Cj(,H420s 466-06-8) see Meproscillarin prostaglandin F2 9,1 l-bis(tetrahydropyranyl ether) (C30H50O7 67899-19-8) see Dinoprostone prostaglandin p2a ll,15-bis(tetrahydropyran-2-yl ether)... 

Although the unsaturated nitrile oxides 124 can be prepared via the aldoxime route (see Scheme 8), the older procedure suffers from the disadvantage that a tenfold excess of allyl alcohol and two additional steps are required when compared to Scheme 15. Therefore, unsaturated nitro ether 123 that can be prepared by condensation of an aldehyde 120 and a nitro alkane followed by Michael addition of alcohol 122, was a useful precursor to nitrile oxide 124 [381. The nitrile oxide 124 spontaneously cyclized to ether 125. This procedure is particularly suitable for the synthesis of tetrahydrofurans (125a-h) and tetrahydropyrans (125i-k) possessing Ar substituents in 72-95% yield (Table 12). The seven-membered ether 1251 was obtained only in 30% yield on high dilution. The acetylenic nitro ether 126 underwent INOC reaction to provide the isoxazole 127. 

A disadvantage of the THP group is the fact that a new stereogenic center is produced at C(2) of the tetrahydropyran ring. This presents no difficulties if the alcohol is achiral, since a racemic mixture results. However, if the alcohol is chiral, the reaction gives a mixture of diastereomers, which may complicate purification and/or characterization. One way of avoiding this problem is to use methyl 2-propenyl ether in place of dihydropyran (abbreviated MOP, for methoxypropyl). No new chiral center... 

The formation of unsymmetrical ethers from the reduction of aldehydes in the presence of tetrahydropyran (THP) ethers is reported (Eq. 182).340... 

An oxidative Prins cyclisation of the allylsilane-tethered a-stannyl ethers offers a route to tetrahydropyrans avoiding the need for catalysis by a Lewis acid (Scheme 17) . 

Haworth methylation of methyl /3-D-glucopyranoside and its 4-benzyl and 4-(tetrahydropyran-2-yl) ethers was investigated in connection with partial-methylation studies on cellulose.267 For the unsubstituted glycoside, the ratios of relative rate-constants k2 k3 k4 k were estimated to be 8 2 1 8, and, for the 4-ethers, it was found that ke> k2> k3 best agreements between calculated and experimental yields were found with the assumption that the rate constant for reaction at HO-3 is doubled when HO-2 is substituted. Later methylation studies,268 performed to low degrees of substitution, with analysis by gas-liquid chromatography, gave k2> k4> k3 for the reactivity... 

On treatment with acrylonitrile in 2% aqueous sodium hydroxide at 0°, tetrahydropyran-2-yl /3-D-glucopyranoside gave the 2-, 3-, 4-, and 6-0-(2-cyanoethyl) ethers (together with some diethers) in yields that, on extrapolation to zero reaction, showed3 9 k2 k3 k4 k6 to be in the ratios of 3 1 2 8 these values represent equilibrium, not rate, constants. The tendency for substitution at 0-6 is a consequence of the greater stability of an ether derived from a primary (compared to a secondary) hydroxyl group, as a result of lower steric interactions in the former. 

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... 

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