Bromodifluoromethyl difluoromethyl

Electrochemical reduction of the 5-(bromodifluoromethyl)-l,2,4-oxadiazole 168 in the presence of tetrakis (dimethylamino)ethylene (TDAE) generates the 5-(difluoromethyl) anion which reacts with aldehydes to give the 5-g. 

Radical addition of dibromodifluoromethane to alkenes followed by sodium borohydride reduction is a convenient two-step method for the introduction of the difluoromethyl group.5 Either one or both carbon-bromine bonds in the intermediate dibromides may be reduced, depending on the reaction conditions. In the case of acyclic dibromodifluoromethane-alkene adducts, the reduction occurs regioselectively to yield the relatively inaccessible bromodifluoromethyl-substituted alkanes. The latter are potential building blocks for other fluorinated compounds. For example, they may be dehydrohalogenated to 1,1-difluoroalkenes an example of this methodology is illustrated in this synthesis of (3,3-difluoroallyl)trimethylsilane. 

Most of these reactions have been extended to ethyl bromodifluoromethyl phos-phonate (Figure 2.15). ° However, conversely to the anions of difluoroacetate, lithiated anions of diethyl difluoromethylphosphonate are easily generated through the deprotonation of ethyl difluoromethyl phosphonate. They are frequently used for the synthesis of difluorophosphonates (cf. Chapter 7)." ° ... 

However, difluoromethylation occurs when nucleophiles intercept difluoro-carbene generated under basic conditions, providing a route to difluoromethyl-ethers of phenols [33] and thiophenols [34]. The reaction with phosphite anion leads to the corresponding difluoromethyl phosphonate (see Sect. 2.3.2) while nucleophilic carbanions such as alkynes [35] also undergo formal alkylation, as do malonates [36,37]. An -difluoromethylaziridine was reported in a reaction with a glycine imine [38]. The scope of the established chemistry is summarised in Fig. 1. Bromodifluoromethylation occurs with a similar range of nucleophiles [39,40], and also with carbonyl-stabilised carbanions such as malonates [41,42]. 

Compounds of formula 15 where Rj is isopropyl or butyl, R2 is haloalkyl (i.e., trifluoroethyl, difluoromethyl or bromodifluoromethyl), Rj is chlorine or bromine... 

Bromodifluoromethyl phenyl sulfone can be transformed to [difluoro(phenylsulfonyl)methyl]trimethylsilane which was employed for fluoride-induced (phenylsulfonyl)difluoromethylation (eq 4). Alternatively, the reaction of bromodifluoromethyl phenyl sulfone with aldehydes mediated by electron-transfer reagent, tetrakis(dimethylamino)ethylene (TDAE), yields (phenyl-sulfonyl)-difluoromethylated alcohols in good yields which can be further transformed to difluoromethyl alcohols and e/B-difluoroalkenes via reductive desulfonylation and Julia olefination, respectively (eq 5). ... 

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