2,2 Difluoro unsaturated acids

Ethyl chlorodifluoroacetate has been used in a silicon-induced Reformatsky-Claisen reaction of allyl chlorodifluoroacetates in the presence ot zinc as a route to 2,2-difluoro unsaturated acids [( S] (equahon 58) When this methodology is applied to chlorodifluoropropargylic esters, the corresponding allenic esters are formed [SS]... 

It is known66 that the hydrofluoric acid-lead tetraacetate reagent leads, with unsaturated steroids, to cis additions of fluorine. This fact suggests that a cis-difluoro adduct (39b, 42b) is the starting point for the ring contractions observed in the preceding examples. 

The double bond in chlorotrifluoroethylene is polarized by back-donation of electrons of fluorine in such a way that the negative charge is on the carbon linked to chlorine and fluorine. Consequently, the difluorome-thylene end of the double bond is more electrophilic and is attacked by the ethoxide anion. Subsequent ejection of fluoride anion gives an unsaturated intermediate, l-chloro-l,2-difluoro-2-ethoxyethylene, compound V. This compound reacts with another ethoxide anion in a similar way and yields l-chloro-2,2-diethoxy-1-fluoroethylene. Nucleophilic addition of a third molecule of ethanol gives the final product, the orthoester of chlorofluoroacetic acid, compound W [75]. 

HNF2 reacts with saturated and unsaturated mono- and diacetals at ambient temperature to 100°C (250) and also smoothly in the presence of a sulfonic acid ion-exchange resin (Amberlyst-15) (140, 276) to give a-difluoroamino ethers (140). These compounds react with a second molecule of HNF2 in the presence of sulfuric acid to give bis(difluoro-amino) derivatives (140). 

The reaction of ketones with diethylaminosulfur trifluoride or related aminosulfur trifluorides in the presence of fuming sulfuric acid affords vinyl fluorides66-72 74 (see Vol. F.lOa, p415). Certain / -oxo esters and pcntanc-2.4-dione react with diethylaminosulfur trifluoride to give a,/i-difluoro-a./f-unsaturated esters and 3,4-difluoropent-3-cn-2-one, respectively.75 In the reaction of y-oxocarboxylic acids with diethylaminosulfur trifluoride cyclization leads to y-fluorobutyrolactones.76... 

Shi, G.Q. Cai, W.L. 5,e-Unsaturated P,P-difluoro-a-keto esters novel synthesis and utility as precursors of P,P-difluoro-a-amino acids. J. Org. Chem. 1985,60,6289-6295. 

The transformation of 4,4-difluoro-3-trifluoromethylbut-3-ene-l-ones 53, easily prepared from hexafluoroacetone (HFA), into 2-fluoro-3-trifluoromethylthio-phenes 54 proceeded on heating with phosphorus pentasulflde [32]. Yields of 2-fluoro-3-trifluoromethylthiophenes 54 depend on the reaction conditions and the progress of the transformation should be monitored by T NMR spectroscopy. The starting compounds were formed by elimination of water from hexafluoroacetone aldols 51 obtained by reaction of HFA with enol silyl ethers in the presence of Lewis acid such as SnCU. The unsaturated ketones 52 were reduced with SnCla and 53 were cyclized to the desired thiophenes 54 with phosphorus pentasulflde [33]. 

Some 4, S -unsaturated-S -fluoroadenosine nucleosides are described in Chapter 20 as well as some purine nucleosides containing the 2 -deoxy-2 fluoro- -D-arabinofuransoyl moiety. A number of dideoxymonofluoro- and dideo difluoro-a-D-glucopyranosyl phosphates have been prepared in order to study their relative rates of acid hydrolysis. The synthesis of a fluorinated 3-deoj -D-glyceric add phosphonate is discussed in Chapter 17 and the conversion of a l,3-anhydro-2-deojty- 2,2-difluoro-D-hexose derivative into a hydrolytically stable thromboxane A2 mimic is covered in Chapter 24. 

Diethyl trimethylsilyloxycarbonylmethanephosphonate" and diethyl car-boxymethanephosphonate " are the preferred reagents for the two-carbon homologation of aldehydes and ketones to give a,/8-unsaturated carboxylic acids, while 2,2-difluoro-l-tosylvinyl-lithium is a novel effective reagent for the preparation of a-keto-acids from carbonyl compounds (Scheme 21). a-Methoxy-aliphatic acids have been prepared from aliphatic aldehydes and chloroform using... 

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