Diols to cyclic ethers

Robinson, P.L., Barry, C.N., Kelly, J.W., and Evans, S.A., Diethoxytriphe-nylphosphorane a mild, regioselective cyclodehydrating reagent for conversion of diols to cyclic ethers. Stereochemistry, synthetic utility, and scope, /. Am. Chem. Soc., 107, 5210, 1985. 

Dehydration of diols to cyclic ethers. The reagent dehydrates a variety of diols to cyclic ethers with formation of triphenylphosphine oxide as the co-product. Yields of cyclic ethers are high from 1,2-, 1,4- and 1,5-diols. Although (Z)-2-butene-1,4-diol is converted into 2,5-dihydrofuran in 95% yield, the (E)-isomer is converted in 35-40% yield into 3,4-epoxy-l-butene.1... 

The scope and synthetic utility of dioxyphosphoranes, and particularly, diethoxytriphenylphosphorane (DTPP), as useful cy-clodehydrating "reagents" for the conversion of diols to cyclic ethers have received only superficial attention (1). The DTPP-diol - ether route has several unique advantages over existing methods (a) the reaction conditions are effectively neutral and mild, (b) the stereoselectivity in the closure of both unsymmet-rical and symmetrical diols to cyclic ethers is high, and (c) the isolation of the product(s) from triphenylphosphine oxide (TPPO) is convenient. 

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%)]. 

Stereochemical information on the mode of cyclodehydration of unsymmetrical diols to cyclic ethers could obviously have important consequences regarding useful, preparative routes to chiral cyclic ethers of high enantiomeric purity. For example, dioxyphos-phorane promoted cyclodehydration of a chiral diol can, in principle, give the enantiomeric ethers by either of two stereochemi-cally distinct routes. Separate stepwise decomposition of oxy-phosphonium betaines, A and B, although proceeded by a number of equilibria could ultimately afford a nonracemic mixture of cyclic ethers. 

Amberlyst-15 was also used as a catalyst for the reaction of alcohols and phenols with tetrahydropyran (Eqn. 22.33). Refluxing a mixture of an alcohol and dimethoxymethane in the presence of a Nafion-H catalyst gave the methoxy methyl ethers in very good yields (Eqn. 22.34). ° Nafion-H was also used to catalyze the conversion of diols to cyclic ethers. ... 

The reaction of a, to-diols or cyclic ethers with a stoichiometric amount of BTMA Br3 in carbon tetrachloride, or in acetic acid in the presence of aqueous Na2HP04 or CH3COONa, at 60-70°C gave lactones. The results are shown in Figure 22. 

The pioneering work of Denney et ai19 on the synthetic utility of oxyphosphoranes has been thoroughly exploited by Evans et al. in demonstrating that diethoxytriphenylphosphorane promotes mild and efficient cyclodehydration of diols (e.g. 11) to cyclic ethers (e.g. 13) via the cyclic phosphorane (12)20>21. Simple 1,2-, 1,4-, and 1,5- diols afford good yields of the cyclic ethers but 1,3-propanediol and 1,6-hexandiol give mainly 3-ethoxy-l-pro-panol and 6-ethoxy-l-hexanol respectively whereas tri- and tetra-substituted 1,2-diols afford the relatively stable 1,3,2- diox-phospholanes. In some instances (e.g. 14), ketones (e.g. 16) are formed by a synchronous 1,2-hydride shift within (15). The synthetic utility has been extended to diethoxyphosphoranes supported on a polystyrene backbone22. 

Halogens are frequently used as oxidation agents and, under two-phase conditions, they can either be employed as ammonium complex halide salts [3], or in the molecular state with or without an added quaternary ammonium catalyst [4]. Stoichiometric amounts of tetra-n-butylammonium tribromide under pH controlled conditions oxidize primary alcohols and low-molecular-weight alkyl ethers to esters, a,cyclic ethers produce lactones [3], and secondary alcohols yield ketones. Benzoins are oxidized to the corresponding benzils (80-90%) by the tribromide salts in acetonitrile in the presence of benzoyl peroxide [5]. 

A range of diols and cyclic ethers were used to carry out alkylation of aromatics (benzene, toluene, xylenes, trimethylbenzenes, naphthalene) in the presence of triflic acid.204 310 In a recent study,311 various methyl-substituted benzene derivatives were alkylated with 1,4-diols [Eq. (5.117)] to form substituted tetralin derivatives in high yields. The transformations involve an intermolecular alkylation step followed by intramolecular alkylation (cyclialkylation). 2,2,5,5-Tetramethyltetrahydrofuran is similarly effective. For example, it alkylates benzene to give octamethyloctahydroan-thracene (98% yield) and reacts with naphthalene to yield octamethyloctahydrote-tracene [Eq. (5.118)]. 

We have excluded pathways which might involve concerted decomposition of dioxyphosphoranes to cyclic ethers with retention of stereochemistry at least for symmetrical 1,2-diols by examining the reaction of d, l-2,3-butanediol with DTPP. The C NMR spectrum of the reaction mixture is consistent only with the cis epoxide exhibiting resonances at 6 12.9 and 52.4 ppm. 

The bromo-alkoxylation route for the synthesis of crown ethers (6,189 5,178) has been adapted to allow the preparation of substituted mono- and di-thia-crown systems (Scheme 49). Once again, one of these sequences uses the cyclization that is effected by a sulphonyl chloride and a base, as does a recently reported preparation of oxo-crown ethers e.g. Scheme 50 for the mono-oxo-series. Studies here imply activation of the carboxy- rather than of the alkoxy-terminus by the sulphonyl chloride. The ester functions reduce the complexing ability of these macrocycles with respect to normal crown ethers. The reduction of oxo-crowns to cyclic ethers, rather than to the diols that might be expected from reduction of a lactone, by LiAlHi has been studied the crown system seems to be necessary, and the involvement of lithium complexes has been suggested. 

Diols react mtramolecularly to form cyclic ethers when a five membered or six membered ring can result... 

Conversion to dialkyl ethers (Sec tion 15 7) On being heated in the presence of an acid catalyst two molecules of a primary alcohol combine to form an ether and wa ter Diols can undergo an intramo lecular condensation if a five membered or six membered cyclic ether results... 

Cyclic ether and acetal polymerizations are also important commercially. Polymerization of tetrahydrofuran is used to produce polyether diol, and polyoxymethylene, an excellent engineering plastic, is obtained by the ring-opening polymerization of trioxane with a small amount of cycHc ether or acetal comonomer to prevent depolymerization (see Acetal resins Polyethers, tetrahydrofuran). 

Sulfurane reagent lor conversion of trans diols to epoxides, generally for dehydration of diols to olefins or cyclic ethers, and as an oxidizing agent... 

The one general exception to the rule that ethers don t typically undergo Sn2 reactions occurs with epoxides, the three-membered cyclic ethers that we saw in Section 7.8. Epoxides, because of the angle strain in the three-membered ring, are much more reactive than other ethers. They react with aqueous acid to give 1,2-diols, as we saw in Section 7.8, and they react readily with many other nucleophiles as well. Propene oxide, for instance, reacts with HC1 to give l-chloro-2-propanol by Snj2 backside attack on the less hindered primary carbon atom. We ll look at the process in more detail in Section 18.6. 

Cyclic ethers can also be formed in a fashion similar to that of the reactions described previously (Eq. 186),306,342 and also result from the reductive etherification of bis(trimethylsilylated) diols and dialdehydes (Eq. 187).343... 

Intramolecular hydrosilylation.1 Hydrosilylation of internal double bonds requires drastic conditions and results in concomitant isomerization to the terminal position. However, an intramolecular hydrosilylation is possible with allylic or homoallylic alcohols under mild conditions by reaction with 1 at 25° to give a hydrosilyl ether (a), which then forms a cyclic ether (2) in the presence of H2PtCl6-6H20 at 60°. Oxidative cleavage of the C—Si bond results in a 1,3-diol (3). 

Under oxidation conditions, a C—C double bond can be functionalized by either two alkoxycarbonyl groups or one alkoxycarbonyl group and one heteroatom. As shown in Scheme 4.14, two ester groups are successfully introduced to styrene in an enantioselective manner, producing a phenylsuccinic ester using a Pd/MeO-BIPHEP complex. mcw-Diols are converted into cyclic ethers in an asymmetric manner when catalyzed by Pd/chiral bisoxazoline. Intramolecular aminopallada-tion followed by carbomethoxylation gives an cyclic amino ester in moderate ee when catalyzed by a Pd/bis(isoxazoline) complex. " ... 

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