Benzyl ether rearrangement

Matsumo et al. [6] reduced the carbonyl group of levoglucosenone and reacted the formed alcohol with thionyl chloride in pyridine. The resulting reaction mixture consisted of three allylic chlorides. The 2-chloro compound with inversed configuration at C-2 (8) was a major product. When this compound was reacted with benzyl alcohol (in the presence of NaH), the rearranged benzyl ether (11) was isolated in an excellent yield. Scheme 11.3 shows the process. 

The diphenolic protoberberine methobromide 285 derived from 283 was refluxed in aqueous ethanolic sodium hydroxide for 12 hr to furnish the quinomethide 287 in 92% yield (Scheme 50). Compound 287 was treated with dimethyl sulfoxide to give rise to the desired diphenolic ochotensimine analog 288 through enolization (150,151). The presence of the phenolic hydroxyl group is essential in this rearrangement because the benzyl ether (284) was recovered unchanged under the same alkaline conditions. 

Nevertheless, another possibility remained for the formation of insertion products, that they might be formed from the O-H insertion product, e.g., dichloromethyl benzyl ether 5, by the Wittig rearrangement of dichloromethoxy-carbanion 4, (Scheme 5, Eq. I).17 However, treatment of independently prepared benzyl dichloromethyl ether 5 with the same base solely gave benzyl chloride, but the insertion product was not obtained (Eq. 2). Hence, a Wittig-type rearrangement process was excluded. 

Asymmetric epoxidation of 10a under standard conditions yields the crystalline epoxy alcohol 2a in 95% ee (91% chemical yield). Treatment of 9a with thioanisol in 0.5N NaOH, in rerf-butyl alcohol solution, gives -after protection of the hydroxyl groups as benzyl ethers- the sulfide a (60% overall yield) through an epoxide ringopening process involving a Payne rearrangement. Since the sulfide could not be hydrolysed to the aldehyde 7a without epimerisation at the a-position, it was acetoxylated in 71% yield under the conditions shown in the synthetic sequence (8a... 

One of the most important side reactions often observed with the [1,2]-Wittig rearrangement is the a,/3 -elimination (equation 3). In fact, treatment of benzyl ether 3 with n-BuLi afforded predominantly the elimination product 4 (equation A f. 

Schollkopf and colleagues have reported that the rearrangement of the enantiopure forms of a-chiral alkyl benzyl ethers 8 followed by oxidation affords ketone 9 of the predominantly retained configuration at the migrating carbon in 20% ee (R = H) and ee (R = Ph) (equation 7)". 

A high level of enantioselectivity in an acyclic system has been reported in the rearrangement of tricarbonylchromium(O) complexes of allyl benzyl ethers using chiral lithium amide base 73 (equation 38) . Upon treatment with 1.1 equivalents of lithium amide 73 and 1 equivalent of LiCl at —78 to —50°C, ether 74 afforded the rearrangement product R)-75 in 80% yield with 96% ee. The effect of substituents on the chemical yields and enantioselectivity of the [2,3]-Wittig rearrangement was also studied (see Table 3). 

Chiral bis(oxazoline) 27 is an effective chiral coordinating agent for enantiocontrol in the [2,3]-Wittig rearrangement. The rearrangement of (Z)-crotyl benzyl ether 84 with f-BuLi/(5, 5)-27 (1.5 equivalents each) in hexane provided [2,3]-shift product (l/ ,25 )-85 in 40% ee (equation 46The feasibility of the asymmetric catalytic version was also examined. In this case, the rearrangement with 20 mol% of 27 in ether was found to provide the same level of enantioselectivity (34% ee). 

The 2-chloro-l,2-difluorovinyl ether of furfuryl alcohol also rearranges at — 35l C despite loss of aromaticity. Methanolysis then affords ester 12, which requires heating to 90 C for rearoma-tization. The 2-chloro-l,2-difluorovinyl ether of benzyl alcohol is sufficiently stable to be isolated but rearranges at room temperature methanolysis affords chlorofluoro(2-tolyl)acetic acid ester 13. Apparently, a 1,3-benzyl shift is not favored in this case, as opposed to other fluorine-containing vinyl benzyl ether systems discussed in Section 5.1.3. 

Use of benzyl alcohol resulted in formation of the benzyl ether corresponding to allyl ethers 52, but attempted Claisen rearrangement resulted in an 82 % yield of the product of a 1,3-benzyl shift (see Section 5.1.3.).20 To demonstrate the utility of the methodology outlined in Table 14, x-oxoester 53a was converted into the corresponding x-amino acid by hydrolysis and reductive animation.20... 

Treatment of the chroman-4-one 1 with benzyl chloride in DMF at 100°C gave the corresponding benzyl ether 2. When the reaction temperature was raised to 153°C, however, the products obtained were the chromone 3 and the flavone 4. It was subsequently shown that the same type of rearrangement could be effected simply by heating 1 with benzyl chloride in DMF containing potassium carbonate. 

This stability order has been used in a reevaluation of the mechanism of the Wittig rearrangement of alkyl benzyl ethers (Eq. (82)). The migration... 

Photolyses of 31-34 in homogeneous solution results in the formation of diphylethanes 39 (5-15%), phenols 38 (5-15%), ortho-hydroxyphenone 36 (40-60%), and para-hydroxyphenones 37 (20-25%). Small amounts of phenyl benzyl ether 35 (3-8%) were also detected. However, photolyses of all of the four esters on NaY zeolite and Nafion only produce ortho rearrangement products 36. Molecular models suggest that esters 31-34 can enter into NaY zeolite internal surface and the inverse micelle of Nafion. We believe that the preference for formation of ort/zo-hydroxyphenones 36 in the products is a consequence of the restriction on diffusional and rotational motion of the geminate radical pair. 

Benzyl methyl ether or allyl methyl ethers can be selectively metalated at the benzylic/allylic position by treatment with BuLi or sBuLi in THF at -40 °C to -80 C, and the resulting organolithium compounds react with primary and secondary alkyl halides, epoxides, aldehydes, or other electrophiles to yield the expected products [187, 252, 253]. With allyl ethers mixtures of a- and y-alkylated products can result [254], but transmetalation of the lithiated allyl ethers with indium yields y-metalated enol ethers, which are attacked by electrophiles at the a position (Scheme 5.29). Ethers with ft hydrogen usually undergo rapid elimination when treated with strong bases, and cannot be readily C-alkylated (last reaction, Scheme 5.29). Metalation of benzyl ethers at room temperature can also lead to metalation of the arene [255] (Section 5.3.11) or to Wittig rearrangement [256]. Epoxides have been lithiated and silylated by treatment with sBuLi at -90 °C in the presence of a diamine and a silyl chloride [257]. 

Hoffmann, R. Ruckert, T. Bruckner, R. [1,2]-Wittig rearrangement of a lifhioalkyl benzyl ether with inversion of configuration at the carbanion C atom. Diastereoselective reductions of cydohexyl radicals with Li arerie. Tetrahedron Lett. 1993, 34, 297-300. 

Matsumoto, M. Watanabe, N. Ishikawa, A. Murakami, H. Base-induced cydization of 1-benzyloxy-2,2,4,4-tetramethylpentan-3-ones intramolecular nudeophilic addition of an anion of a benzyl ether to the carbonyl moiety without Wittig rearrangement or protophilic decomposition. Chem. Commun. 1997, 2395— 2396. 

When chiral substrates were employed in the cascade reaction, good transfer of the chiral information was observed (Scheme 7.43).119 Excellent diastereoselectivity was obtained with 152g, containing an allylic methyl group and even 152h, which contained a benzyl ether substituent that would lie outside the chairlike transition state (TS-156), controlled the facial selectivity of the [3,3]-sigmatropic rearrangement. 

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