Tetrahydropyran-2,4-diol

Three different carbonyl components are assembled to tetrahydropyran-2,4-diols by two successive diastereose-lective aldol reactions. Tin(rv) enolates provide high selectivity as compared with other metals (Equation (74)).227,228... 

Starting with geraniol (126), Sharpless asymmetric epoxidation [68] proceeded in 95% yield and with 93% ee (see Scheme 29) [69]. Hydrobromination of the alkene was achieved under standard conditions using NBS in THF and water (5 1) to afford a 64% yield of diastereomeric bromo alcohols (127). Cyclization to the tetrahydropyran diol was accomplished by treating 127 with camphorsulphonic acid in diethyl ether, followed by diol cleavage with sodium periodate to give a mixture of aldehydes 128 and 129. Upon... 

A three-component domino process consisting of an ene reaction followed by the addition of an allylsilane to afford polysubstituted tetrahydropyrans in generally good yield was described by Marko and coworkers [115]. However, the nature of the products formed in this process depends heavily on the Lewis acid employed as a catalyst. Thus, reaction of the allylsilane 4-333 with an aldehyde in the presence of BF3-Et20 led to the domino products 4-334, whereas in the presence ofTiCL the diol 4-332, and in the presence of Et2AlCl the alcohol 4-335, were obtained (Scheme 4.74). The latter compound can then be transformed in stepwise manner to 4-334, using the same aldehyde as previously. However, it is also possible to use another aldehyde to prepare tetrahydropyrans of type 4-336. 

The same group also conducted a series of competition experiments with diols such as 36, which show that AgN03 and HgCl2 behave similarly in Scheme 15.8, the results for AgN03 are depicted [17]. It is obvious that a selective cyclization to a dihydropyran 37 is dependent on an alkyl chain such as R1 with R1 = H, for both R2 = H and R2 = alkyl an almost 1 1 mixture of 37 and tetrahydrofuran 38 was observed. The competition of a two-carbon chain with a four-carbon chain in 39 leads to a 2 1 mixture of the dihydropyran 40 as the major product and the tetrahydropyran 41 as the minor product. 

Tetrahydrofuran itself can be opened using either the stoichiometric or the catalytic version of arene-promoted lithiation, but both cases need the activation by boron trifluoride. The catalytic reaction was performed by treating the solvent THF 324 with the complex boron trifluoride-etherate and a catalytic amount (4%) of naphthalene. The intermediate 325 was formed. Further reaction with carbonyl compounds and flnal hydrolysis yielded the expected 1,5-diols 326 (Scheme 95), which could be easily cyclized to the corresponding substituted tetrahydropyrans under acidic conditions (concentrated FlCl). 

Many examples of the synthesis of tetrahydropyrans are based on the cyclization of 1,5-diols and compounds which can provide a similar electrophilic site for ring closure. Thus, pentan-l,5-diols can be quantitatively cyclized to the pyran in the presence of BuSnCl3 (88G483). 

The acid-catalyzed cyclization of some allyl 1,7-diols leads to tetrahydropyrans (64HCA602). The reaction involves dehydration at the allyl position. 

Cyclodehydration of 1,4- and 1,5-diols These diols are converted into tet-rahydrofurans and tetrahydropyrans, respectively, when heated with HMPT (0.3 equiv.). 

The method is readily adapted for the preparation of dibromides from diols. Typical examples are provided in Expt 5.54. The cyclic ethers tetrahydrofuran and tetrahydropyran are readily cleaved by the hydrobromic acid-sulphuric acid medium, and this provides an alternative and convenient preparation of the corresponding a, co-dihalides. 

An alternative reagent, which is particularly effective for the conversion of diols into diiodo compounds, is a mixture of potassium iodide and 95 per cent orthophosphoric acid (Expt 5.58). The reagent also cleaves tetrahydrofuran and tetrahydropyran to yield the corresponding a, co-diiodo compounds [cf. the hydrobromic acid-sulphuric acid reagent, Section 5.5.2, p. 559]. 

We have systematically examined the facility with which DTPP promotes the cyclodehydration of simple diols to cyclic ethers 1,3-propanediol (1) - oxetane (2) (2-5%) 1,4-butanediol (3) te-trahydrofuran (4) (85%) 1,5-pentanediol (5) - tetrahydropyran (6) (72%) 1,6-hexanediol (7) - oxepane (8) (55-68%). Increased alkyl substitution at the carbinol carbon s gnificantly diminishes the facility for cyclic ether formation. For example, a mixture of meso- and d, 1 —2, 6-heptanediol gave only 6-10% of the cis- and trans-2,6-dimethyltetrahydropyrans when treated with DTPP. While diol 1 resists cyclodehydration with DTPP to oxetane, some 2,2-di-substituted 1,3-propanediols are readily converted to the appropriate oxetanes [e.g., 2-ethyl-2-phenyl-l,3-propanediol -> 3-ethyl-3-phenyloxetane (78%)]. 

Optically active co-bromocyanohydrins yield 2-cyano-tetrahydropyrans without racemisation (95CC989) and both the unsaturated alcohol (1) and the diol (2) afford the same tetrahydropyran through stereospecific cyclisation of a common episulfonium ion (95TL1909). 

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