Difluorovinyl ether

The author next tried to stabilize the PGI2 structure by introducing second fluorine atom to the 7-position. However, it had been unknown to make such a difluorovinyl ether unit in the literature. We studied difluorination and Wittig reaction as key steps in the synthetic route of the target difluoro-PGl2 from the Corey lactone. After searching the difluorination reaction, it was found that fluorination with A/-fluorobenzenesulfonimide in the presence of potassium bis(trimethylsilyl) amide and manganese dibromide effectively provided the desired difluoride (Table 7) [106]. 

The 2-chloro-l,2-difluorovinyl ether of furfuryl alcohol also rearranges at — 35l C despite loss of aromaticity. Methanolysis then affords ester 12, which requires heating to 90 C for rearoma-tization. The 2-chloro-l,2-difluorovinyl ether of benzyl alcohol is sufficiently stable to be isolated but rearranges at room temperature methanolysis affords chlorofluoro(2-tolyl)acetic acid ester 13. Apparently, a 1,3-benzyl shift is not favored in this case, as opposed to other fluorine-containing vinyl benzyl ether systems discussed in Section 5.1.3. 

Tributylsilyl)trifluoroethene has been used as a precursor to the vinylic fragment.1516 This variation of the original methodology10 avoids the need for butyllithium, since proto-desilylation to give allyl difluorovinyl ether intermediates 34 is achieved with tetrabutylam-monium fluoride. The 2-fluoroalk-4-enoie acid derivatives 35 are produced in a one-pot procedure (Table 11). Various mechanistic possibilities have been discussed in order to account for the stereochemical outcome.16 The need for two equivalents of allylic alcohol limits the utility of this method. 

Metcalf et al. (56) (Scheme 39) prepared difluorovinyl ethers (131) by base treatment of 130 and found that spontaneous rearrangement to the difluoroaldehyde (132) occurred under the reaction conditions. In similar fashion (Scheme 40) 133 was converted to 135 via the enol 134 (30). Alternatively, the enolate can also be trapped as the trimethylsilyl ether (137) prior to rearrangement (Scheme 41) (59). 

A number of Claisen rearrangements of allyl vinyl ethers have been reported. Thus allyl 2-diloro-l,2-difluorovinyl ether, prepared by the alkoxide-catalysed addition of allyl alcohol to chlorotrifluoroethylene, followed by dehydrofluoiination with n-butyl-lithium at —SO °C, rearranges at-35 C ... 

A postulated six-membered intermediate (Figure 2), formed by the attachment of the chiral boron reagent 1 to the phenolic hydroxy group, and the subsequent coordination of the ethereal oxygen to the boron atom can be used to explain the stereochemical outcome of the rearrangement. The 5r face of the difluorovinyl ether moiety is shielded by the tolylsulfonyl groups thus, the allyhc moiety approaches preferably from the Re face to avoid steric interaction with the aromatic group in the chair-like transition state. 

Scheme 10.36 Claisen rearrangements of difluorovinyl allyl ethers with sulfurcontaining boron catalyst.

The scope of this methodology was extended to the enantioselective rearrangement of difluorovinyl allyl ethers by these authors, furnishing a novel powerful tool for the synthesis of chiral p-substituted a,a -difluorocarbonyl compounds. As shown in Scheme 10.36, moderate to good enantioselectivities... 

Fluorine substituents on the C—C double bond greatly accelerate Claisen rearrangement. For instance, difluorovinyl prenyl ether 83 rearranges at 100°C, while nonfluorinated vinyl prenyl ether rearranges at 200°C [ 1 ]. The chemoselective transformation of 76 to 75 reveals also a favorable fluorine-directed rearrangement [2]. 

Difluorovinyl methyl ethers and aminal bis(carbamates) or bis(sulfonamides) react in the presence of Tf20 to generate /3-amino-a,a-difluoroketones (eq 11) ... 

Difluorovinyl ahyl ethers can be similarly rearranged. The preparation of 8-subshtuted, a,a-difluorocarbonyl compounds (5) is possible upon treatment of 4 with 1.5 equiv of (5,5)-1 in the presence of 1.5 equiv of EtsN in CH2CI2 at -78 °C, and then stirring at ambient temperature (eq 2). 

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