Oxonium ions, secondary preparation

Trialkyloxonium salts can also be prepared by the reaction of secondary oxonium ion salts with diazoalkanes93 [Eq. (4.16)]. 

Ethers of DHA are usually prepared by treatment of DHA 2 (a p 50 50) with an appropriate alcohol in the presence of BF3 and Et20. The stereochemistry of this reaction has been intensively investigated and discussed [38], in particular by Haynes el al. [18c, 24, 39], This process is less efficient with fluoro-alcohols (RfOH), because they are poor nucleophiles. For instance, the reaction of trifluoroethanol with DHA [40], in the presence of BF3 and Et20 in ether, yielded ether 9a (67%), and dehydrodeoxoartemisinin 10 (20%) resulting from the competing deprotonation of the intermediate oxonium ion 11 (see Scheme 6.3) [27, 30], However, a secondary fluoro-alcohol and pentafluorophenol did not react at all (see Table 6.1). 

Acid-catalysed addition of primary, secondary, and tertiary alcohols to 3,4-dihy-dro-2//-pyran in dichloromethane at room temperature is the only general method currently in use for preparing THP ethers and the variations cited below concern the choice of acid. The reaction proceeds by protonation of the enol ether carbon to generate a highly electrophilic oxonium ion which is then attacked by the alcohol. Yields are generally good. Favoured acid catalysts include p-toluenesulfonic acid or camphorsulfonic acid. To protect tertiary allylic alcohols and sensitive functional groups such as epoxides, the milder acid pyridinium p-toluenesulfonate has been employed (Scheme 4.316]. A variety of other acid catalysts have been used such as phosphorus oxychloride, iodotrimethylsilane- and bis(trimethylsilyl)sulfate. but one cannot help but suspect that in all of these cases, the real catalyst is a proton derived from reaction of the putative catalysts with adventitious water. Scheme 4.317 illustrates the use of bis(trimethylsilyl)sulfate in circumstances where other traditional methods failed. - For the protection of tertiary benzylic alcohols, a transition metal catalyst, [Ru(MeCN)2(triphos)](OTf)2 (0.05 mol%) in dichloromethane at room temperature is effective. ... 

Nokami reported a study that documents the asymmetric rearrangement of chiral oxonium ions (Scheme 16.19) [97]. These reactive intermediates are generated upon condensation of optically active alcohols and aldehydes. The requisite alcohol 158 was prepared by diastereoselective addition of cro-tylmagnesium chloride 156 to menthone 157. Subsequent treatment of the alcohol with an aldehyde such as PhSCH2CH2CHO under acidic conditions induced formation of 159. The ensuing [3,3]-rearrangement gave 160, and in situ hydrolysis of the chiral auxiliary afforded the secondary homoallylic alcohol with excellent optical purity (99% ee). 

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