Fluorides, acyl from alcohols

As hydrogen fluoride functions with equal ease in alkylation with olefins, alkyl halides, or alcohols, and in acylation with acids, acid anhydrides as well as acyl halides, a wide choice of reagents is possible and a separate operation of the reconversion of them is often saved. With aluminum chloride the alkyl halides and acyl halides are the preferred reagents and frequently must be made from more plentiful, cheaper, and readily available substances. 

Tetrafluoroethene has been used as a 2-carbon difluoroacetic acid equivalent, methodology developed by Normanl and co-workers, in the synthesis of inhibitors of Cobra venom phospholipase A2.13 Conversion of the allyl alcohols into the 2,2-difluoropent-4-enoic acids 32 is performed in one pot. The crude acids 32 are then converted into the methyl esters 33. Although esters 33 can be obtained directly from the acyl fluorides 29, as originally described by Normant and co-workers,10 a two-step procedure facilitates the workup after the Claisen rearrangement. 

In the preferred literature, most fluoroformates are prepared from their analogous chloroformates through halogen exchange using excess KF activated by a little 18-Crown-6. However, this method proved to be impractical for tertiary alkyl fluoroformates and/or benzyl fluoroformates, either because the corresponding chloroformates are not stable or because of the lack of selectivity of the fluoride attack. Acylation of the respective alcohols with COF2 or COFCI requires complex equipment not accessible to standard laboratories and/or multipurpose plants. 

Crafts process is to generate carbonium ions from the alkyl or acyl halides. It would be expected, then, that a number of other combinations of starting materials and reagents which lead to carbonium ions should be capable of effecting acylation or alkylation. Indeed we find that olefins (p. 35), alcohols (p. 36), ethers (p. 36), and esters (p. 37) can be used as starting materials for aromatic alkylation reactions in the presence of such catalysts as boron trifluoride, sulfuric acid, or anhydrous hydrogen fluoride.69 Acylations can be carried out with acids (p. 37),64 acid halides (p. 230), and acid anhydrides (p. 37). The Fries reaction65 (in which phenolic esters are converted to hydroxy aromatic ketones by means of aluminum chloride) appears to be an example of a typical acylation reaction in which the ester itself acts as the source of an acyl carbonium ion ... 

Ort/io-selectivity is generally observed in the reactions of 2,4-dichloro- and 2,4-difluoro-nitrobenzene with alkoxide and thiophenoxide ions [199]. Also in less activated systems, nucleophiles generated from phenols and thiophenols with potassium fluoride-alumina and 18-crown-6-polyether will react in DMSO with cyano- or nitro-substituted fluoro- or chloro-benzenes [200]. Interestingly, the reaction of difluorobenzenes with two diffoent alcohols can occur sequentially. Introduction of the first etho" function deactivates the ring, and use of more forcing conditions allows substitution of the second fluorine [201]. Consecutive displacements of fluorine and nitro groups have been observed in the reaction of ort/io-fluoronitrobenzene with chiral acyl bicyclic lactones in a highly enantioselective synthesis of spirooxindoles [202]. 

---