Cyclic ethers, rearrangement

The formation of the six-membered ether ring via epoxy ester-ortho ester cyclic ether rearrangement supports the hypothesis that epoxy ester-ortho ester cyclic ether rearrangement may be involved in the biosynthesis of ladder-type marine polyether toxins. This reaction represents a biomimetic preparation of medium ring cyclic ethers. 

Polyether Polyols. Polyether polyols are addition products derived from cyclic ethers (Table 4). The alkylene oxide polymerisation is usually initiated by alkah hydroxides, especially potassium hydroxide. In the base-catalysed polymerisation of propylene oxide, some rearrangement occurs to give aHyl alcohol. Further reaction of aHyl alcohol with propylene oxide produces a monofunctional alcohol. Therefore, polyether polyols derived from propylene oxide are not truly diftmctional. By using sine hexacyano cobaltate as catalyst, a more diftmctional polyol is obtained (20). Olin has introduced the diftmctional polyether polyols under the trade name POLY-L. Trichlorobutylene oxide-derived polyether polyols are useful as reactive fire retardants. Poly(tetramethylene glycol) (PTMG) is produced in the acid-catalysed homopolymerisation of tetrahydrofuran. Copolymers derived from tetrahydrofuran and ethylene oxide are also produced. 

Diepoxidation of a diene Diepoxidation of the diene 1 with m-chloroper-benzoic acid gives a mixture of the d,l- and meso-diepoxides, whereas Sharpless epoxidation results in d- or 1-2 by a double asymmetric epoxidation. On treatment with base, 2 rearranges to the diepoxide a and then cyclizes to the meso-tetra-hydrofuran 3, a unit of teurilene, a cytotoxic C, -cyclic ether of red algae. This... 

The efficient rearrangement of these cyclic ethers may stem from the favorable juxtaposition of the reactive centers. Rearrangement of related acyclic substrates is notably less efficient. 

The rearrangements of 3-methylbut-l-ene oxides" and l,2-epoxybut-3-ene on lithium phosphate have been studied, and a detailed theoretical study of the rearrangement of allene oxide (342) to cyclopropanone (344), which shows that the transformation proceeds via an intermediate oxyallyl (343), has been presented. It has been shown that aldehydes, ketones, and cyclic ethers are all produced... 

The acetal [1,2]-Wittig rearrangement protocol is also applicable to the synthesis of medium-sized cyclic ethers. For example, a reaction of the 9-membered cyclic acetal 37 with lithium piperidide provides the 8-membered ring ether 38 in good yield along with high diastereoselectivity (equation 20) . 

The pioneering work on enantioselective [2,3]-Wittig rearrangement was carried out by Marshall and Lebreton in the ring-contracting rearrangement of a 13-membered cyclic ether using lithium bis(l-phenylethyl) amide (63) as a chiral base (equation 34). Upon treatment with a (S,S)-63 (3 equivalents) in THF at —70 to —15 °C, ether 64 afforded the enantioenriched [2,3]-product 65 in 82% yield with 69% ee. The reaction was applied in the synthesis of (+)-aristolactone (66). 

Besides [2,3]-sigmatropic rearrangement and [l,2]-shift reactions, the oxonium ylide may undergo other reactions. The oxonium ylide intermediate can be trapped by a protic nucleophile. Oku and co-workers have developed a method for ring expansion of cyclic ethers through oxonium ylide formation. Bicyclic oxonium ylide... 

Polyether Polyols. Polyether polyols are addition products derived from cyclic ethers (Table 1). The alky lens oxide polymerization is usually initiated by alkali hydroxides, especially potassium hydroxide. In the base-catalyzed polymerization of propylene oxide, some rearrangement occurs to give allyl alcohol. 

Further, medium-sized lactones have been prepared by a thermal elimination-Claisen rearrangement sequence, of unsaturated selenoxide cyclic acetals (equation 198)710. The reaction affords reasonable yields of these useful lactones upon treatment with DBU and a siloxy species at 185 °C. The reaction has been used as the key step in the synthesis of (-l-)-laurencin, which contains an 8-membered cyclic ether moiety711. 

Although chlorobenzene is rather inactive in usual reactions, its activity is enhanced by complex formation, and two products are formed by the reaction of stabilized carbanions on the complexed chlorobenzene 207, depending on the conditions [44], The anion of a-methy l propionitrile reacts at the meta position at —78 °C, and the mete-substituted product 208 is obtained by oxidation with I2. However, equilibration (rearrangement) of the carbanion occurs at 25 °C, because the attack of the carbanion is reversible, and the substitution product 209 of the chlorine is obtained. The fluorobenene 210, coordinated by Cr(CO)3, is very reactive. Reaction of y-butyrolactone to the o-lithiated fluorobenzene 211 gives rise to the alkoxide 212, which displaces the fluoride intramolecularly to give the cyclic ether 213 [52], In other words, the complex 211 can be regarded as the 1,2-dipolar synthon 214. However, Cr(CO)3-complexed aromatic bromide and iodide can not be used for the nucleophilic substitution. 

The mechanism is in agreement with the observation46 that crotyl ethers rearrange more rapidly than allyl ethers, because the 7-methyl group would promote the electronic shifts indicated. The cyclic mechanism as written does not explain the abnormal rearrangement, which involves the shift of two hydrogens, but this may involve a cyclic intermediate in which the /3-carbon becomes attached to the ortho carbon atom. 

Wallace, T. J., and R. J. Gritter The Free Radical Chemistry of Cyclic Ethers. III. A Free Radical Rearrangement Reaction. J. org. Chem. 27, 3067 (1962). 

Various cycloalkanones were converted to rearranged cyclic ethers in the presence of a catalytic amount of hydrogen fluoride in 16-18% yield, while increasing the amount of hydrogen fluoride resulted in a higher conversion of starting ketone, but the ethers were further fluorinated on the aromatic ring23,24,107. 

Williamson ether synthesis Claisen rearrangement Cyclic ethers ... 

A related reaction occurs on irradiation of a hypochlorite (Scheme 2). The alkoxyl radical can again abstract a hydrogen atom in a l,S-shift, and the final chloro alcohol can be cyclized to form a tetrahydro-furan. Some processes lead directly to the cyclic product For instance, an alcohol with an accessible 8-hydrogen can be directly converted to a tetrahydrofuran on refluxing with lead tetraacetate. In a related reaction, treatment of an alcohol with silver carbonate and bromine can lead to the cyclic ether by initial formation of a hypohalite. The cyclization occurs when the rearranged radical is converted to a cation, either by oxidation with Pb(OAc)4 or by silver-assisted loss of halide ion. Hypoiodites are also fiequent-ly used, generated in situ. ... 

---