Bromoetherification

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>. 

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. 

Fig. 3.36. Stereoselective iodolactonization (top) and stereoselective bromoetherification (bottom). See Figure 1.30 for the dehalogenations of the iodolactone and of the bromoether shown.

Arylboronic acids possessing an ortho-1-alkenyl or 2-alkenyl group underwent preferential bromoetherification with NBS in aqueous THF, whereas the B-C bond cleavage predominated under basic pH s (Equation (78)).449... 

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. 

Dihydroxylation of the terminal alkene of 90, followed by oxidative cleavage to the aldehyde allowed the authors to isolate compound 86 in an enantiomerically pure form. However, the low yielding (24%) bromoetherification step led the authors to search for a more efficient method. 

The second strategy was to implement the bromoetherification at a later stage in an effort to increase the stereoselectivity for the bromonium ion cyclization. Thus, compound 95 was synthesized from... 

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 has been used for the enantioselective synthesis of polysubstituted furans170,171. calonectrin and deoxynivalenol172. The final products, again, do not contain bromine. 

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. 

This bromoetherification is a variant of the more famiiiar mechanism of bromoiactonization (pp. 568-9 of the textbook). 

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... 

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). 

To introduce an epoxy group on the terminal double bond, the other alkene function was protected by bromoetherification to produce the bromo ether, which was desilylated and compound 452 provided. In the final two steps, olefin 453 was epoxidized with m-CPBA and deprotected with a zinc-silver complex to obtain ( )-verrucarol (454) (Scheme 8.13). 

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]. 

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