Bromoetherification reaction

Semiempirical MO methods have been employed to determine the reaction surface for intramolecular bromoetherification reactions. Bromonium ions have not been identified as intermediates instead, the additions involve the formation of a weak olefin/Br+ 7r-complex, which is subsequently captured by a proximate nucleophile196. 

Bromoetherification, the addition of the elements of Br and OR to a double bond, is a common method for constructing rings containing oxygen atoms. This reaction has been used in the synthesis of the polyether antibiotic monensin (Problem 21.40). Draw a stepwise mechanism for the following intramolecular bromoetherification reaction. 

An efficient and highly enantio- and diastereoselective bromocycliza-tion-desymmetrization of olefmic 1,3-diols used a cyclic sulfide as catalyst. Olefmic 1,3-diols as substrates gave substituted THFs with up to three ste-reogenic centers, with two tetra-substituted carbons. This protocol represents the first case of a monofunctional C2-symmetric Lewis basic sulfide-catalyzed enantioselective bromoetherification reaction, which was applicable to the synthesis of a key intermediate to the orally active antifungal drug posaconazole (Noxafil) (14JA5627). 

By using the same phosphoric acid catalyst and identical reaction conditions employed in bromoetherification reactions (Scheme 13.28), the bromoaminocyclization of 1,2-disubstituted olefin substrates provided chiral pyrollidines with vicinal stereocenters [61]. 

Kishi described an elegant example of a bromoetherification reaction for effecting acyclic stereocontrol (Scheme 9.29) [162], In this case, bromide 219 was isolated as a single isomer in 57 % yield upon treatment of diolefin 218 with NBS. The presence of an allylic stereogenic center with two substituents of considerably different steric demands (Me versus 4-(3-methylbut-l-ene)) in 218 leads to a system in which interactions play a dominant role in controlling the stereochemical outcome of the cyclization. These synthetic efforts leading to intermediate 219 culminated in the total synthesis of the polyether antibiotic monensin (220) [163]. 

Haloetherification remains one of the most popular approaches towards tetrahydrofuran skeletons. Yus reported a double iodoetherification reaction promoted by a silver salt, affording l,7-dioxaspiro[4.5]decanes, and an example is shown in the scheme below <06T2264>. Kumar and Singh also reported an iodoetherification pathway to form 2,3-diphenyltetrahydrofurans <06T4018>. A bromoetherification converted 3-butenols into bromotetrahydrofurans <06TL5751>. 

Bromoetherification. A desymmetrization method for meso-1,2-diols involves acetalization with a 5-norbomene-cnrfo-2-carbaldehyde and treatment with NBS-collidine and MeOH in the first two steps. One hydroxyl group of such an adduct is then released by reductive elimination, which can be protected. Reaction of the mixed acetal at this stage with another equivalent of the meso-diol completes a cycle. 

Other varieties of this sort of reaction include bromoetherification (where the nucleophilic component is an alcohol rather than a carboxylic acid). Kishi30 used this reaction to form one of the tetrahydrofuran rings 124 to 125 in his synthesis of Monensin but he used NBS instead of bromine as the source of electrophilic bromine.31... 

Bromoetherification. The combination of NBS with an alcohol to functionalize an alkene is analogous to bromohydrination. Interestingly tricyclic skeletons can be constructed from such adducts in one operation based on dehydrobromination, isomerization of an alkyne to an allene, and intramolecular Diels-Alder reaction. 

Bromoetherification of alkenes can be achieved using NBS in the desired alcohol as the solvent. The reaction of 1,3-dichloropro-pene with NBS in methanol yields an a-bromo dimethyl acetal in the first step in a convenient synthesis of cyclopropenone. Using propargyl alcohol the reaction depicted in eq 22 has been extended to an annulation method for the synthesis of a-methy-lene-y-butyrolactones. Intramolecular bromoetherification and bromoamination reactions are generally very facile (eq 23). In natural products synthesis, bromoetherification has been used for the synthesis of cyclic ethers (by subsequent debromination, see... 

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