Trifluoromethyl alcohols, activated synthesis

Synthesis of trifluoromethylated compounds 152 has been achieved via ester-enolate [2,3]-Wittig and [3,3]-lreland-Claisen rearrangements. Perfluorocyclo-butane phosphonium ylides, e.g. 153, have been used as a masked fluoride anion source in their reactions with alcohols and carboxylic acids which lead to alkyl-and acyl-fluorides. Ylides 153 are also reported to cleave Si-C and Si-O bonds, cause dimerisation of fluoro-olefins, and also react with acid chlorides or other activated aromatic compounds under halogen exchange. ... 

The synthesis of fluoroalkyl and chlorofluoroalkyl ethers occurs readily by base-catalyzed nucleophilic addition of alcohols to haloalkenes. An example is the s3mthesis of the alkyl 2,2-dichloro-l,l-difluoroethyl ethers, where R is methyl or 1° or 2° alkyl (equation 9.80). Nucleophilic addition can also occur with alkynes that are activated by the presence of groups such as trifluoromethyl. An example is the addition of methoxide to hexafluoro-2-but)me (87) to produce the methoxy ether with trans trifluoromethyl groups (88, equation 9.81). Note that the orientation of addition to the alkyne is anti, a pattern that is frequently— but not always—observed. ... 

Fluorinated analogues of biologically active molecules have received, in the past twenty years, an increasing interest. The Claisen-Johnson rearrangement applied to fluoro-substituted allylic alcohols appeared rapidly as a method of choice for the synthesis of various fluoro-polyfunctionalized compounds. Claisen rearrangement and Claisen-Johnson rearrangement of trifluoromethyl allylic alcohols 533 developed by Ishikawa [131] afforded selectively the anticipated esters 534 and 535. Z,syn-config-... 

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