Benzyl ethers, -Wittig rearrangement

The rearrangement of an ether 1 when treated with a strong base, e.g. an organo-lithium compound RLi, to give an alcohol 3 via the intermediate a-metallated ether 2, is called the Wittig rearrangement. The product obtained is a secondary or tertiary alcohol. R R can be alkyl, aryl and vinyl. Especially suitable substrates are ethers where the intermediate carbanion can be stabilized by one of the substituents R R e.g. benzyl or allyl ethers. 

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. 

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. 

Miscellaneous The treatment of allyl 1-bromo-2-naphthyl ether 43 with f-BuLi affords benzyl alcohol 44 via a sequential reaction consisting of bromine-lithium exchange, and anion translocation, followed by a [1,2]-Wittig rearrangement (equation 23). ... 

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 Wittig rearrangement is the base-catalyzed 1.2-shift of an alkyl, allyl. benzyl, or phenyl group of an ether from oxygen to carbon. A patent claim describes the conversion of aryl arylmethyl ethers such as 21 into diarylmethanols such as 22.14... 

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

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. 

Alkylation of benzyl alkyl ethers. The anion of a benzyl alkyl ether is unstable and rearranges to the corresponding alkoxide (Wittig rearrangement). However, coordination of the ether to CrfCO), stabilizes the oi-anion and permits alkylation to give an a-substituted benzyl ether. Complexation also stabilizes the anion of a benzyl alkyl sulfide. The products undergo decomplexation on exposure of ether solutions to air and sunlight (overall yields 65-80%). 

Eisch, J. J., Kovacs, C. A., Rhee, S.-G. Rearrangements of organometallic compounds. X. Mechanism of 1,2-aryl migration in the Wittig rearrangement of a-metallated benzyl aryl ethers. J. Organomet. Chem. 1974, 65, 289-301. 

Hauser noted that diallyl ether (8) also undergoes Wittig rearrangement upon base treatment and suggested that product formation could involve either a 1,2-shift or a cyclic mechanism (equation 3). Later studies by Schdllkopf and Makisumi with substituted allylic ethers (10,11 and 14-16 equations 4 and 5) pointed to a cyclic (SnO mechanism a process allowed by the Woodward-Hoffmann rules. The diastereoselectivity of the reaction was not determined in these cases, but Schollkopf subsequently found that benzyl rrans-crotyl ether (20 equation 6) affords mainly the anti products upon rearrangement of ether (20) with BuLi in THF. Rautenstrauch observed a 1 1 mixture of syn and anti products upon rearrangement of ether (20) in the presence of TMEDA, whereas the cis isomer (23) gave only the syn product (22 equation 7). ... 

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