2-bromo-3,3,3-trifluoropropene

Recently, 3,3,3-trifluoro-2-propenyl zinc reagent has been prepared by the reaction of 2-bromo-3,3,3-trifluoropropene with Zn(Ag) and TMEDA in THF in good yield [169]. TMEDA is essential to the preparation of this zinc reagent, presumably by formation of a chelate structure which can stabilize the zinc reagent (Scheme 58). 

A 1-L, 3-necked, round-bottomed flask was equipped with magnetic stirrer, pressure-equalizing addition funnel with N2 inlet, low temperature thermometer, and a Friedrich condenser with N, outlet. The outlet was attached to two traps in series. The first was cooled in a Dewar of salt/ice water (- 15 C) and the second in a Dewar of dry ice/i-PrOH (— 78 C). 2-Bromo-3,3,3-trifluoropropene (50 g, 0.286 mol) and hexane (250 mL) were added to the flask. 1.6 M BuLi in hexane (190 mL, 0.304 mol, commercial) was added to the addition funnel. The flask was cooled with a hexane slush bath by addition of liquid N2 until the temperature of the solution inside the flask was - 85 °C. Then the BuLi soln was added over a period of 25 min at such a rate that the temperature remained below - 80 C. The slightly cloudy, yellowish solution was allowed to stir for an additional 10 min. Then, the hexane slush was removed, Upon reaching - 30 C, a gelatinous precipitate formed and the temperature rapidly rose to 28 "C. The volatile product was removed from solution by heating the mixture at reflux for 30 min with a slow flow of N2 through the system. The product was obtained from the dry ice trap yield 21 g (97%). 

Dipole cycloaddition of diazomethane to 2-bromo-3,3,3-trifluoropropene 48 (Scheme 12.6) followed by dehydrobromination affords 41, quantitatively. A copper-catalyzed A-phenylation reaction of 41 with phenyl bromide or iodide under mild conditions provides A-phenyl-3-trifluoromethylpyrazole 47 in excellent yields. 

Trifluoroisopropenylzinc reagent is prepared in nearly quantitative yield by the direct zincation of 2-bromo-3,3,3-trifluoropropene in the presence of TMEDA. This organozinc reagent readily undergoes Negishi coupling with a wide variety of aryl halides. Various functional groups, such as Br, Ac, OMe, NO2, OAc, and CHO, are tolerated. Excellent yields are achieved in most cases. However, o-anuno- and acetylamino-substimted... 

In the reaction of 2-bromo-3,3,3-trifluoropropene with pyridinium ylides cycloaddition occurred readily leading to I-CF3 derivatives of indolizines [21]. Similar reaction took place in the cases of pyridazinium and isoquinolinium ylides. 

Fuchikami T, Ojima I (1982) New and direct route to 5-trifluoromethyl-5,6-dihydrouracils by means of palladium complex catalyzed ureidocarbonylation of 2-bromo-3,3,3-trifluoropropene. Tetrahedron Lett 23 4099 100... 

Under stirring, a precooled solution of 2-bromo-3,3,3-trifluoropropene (3.5 g, 20 mmol) in tetrahydrofuran is added dropwise to a solution of lithium diisopropylamide (prepared from disopropylamine and -butyllithium, 20 mmol each) in tetrahydrofuran (40 mL) and hexanes (25 mL) kept in a dry ice/methanol bath. After another 5 min at -75 °C, 3-benzyloxypropanal (3.3 g, 20 mmol) is added. The mixture is allowed to reach ambient temperature before being treated with 1.0 M hydrochloric acid (25 mL), extracted with ethyl acetate (3 x 15 mL), and concentrated. The combined organic layers are evaporated and the residue left behind is purified by column chromatography on silica gel 4.76 g (92%). ... 

Commercially available 2-bromo-3,3,3-trifluoropropene (2-BrTFP) 44 is recognized as an attractive coupling partner. 

Interestingly, the presence of a CFs-substituent facilitates considerably the zinc insertion. Thus, 2-bromo-trifluoropropene reacts with Zn/Ag couple in the presence of TMEDA leading to the expected zinc reagent 3S in 93% yield [35c-e]. 

The strongly electron-withdrawing trifluoromethyl group destabilizes an adjacent carbocation and reduces the rate constant for addition of hydrogen halides to an alkene. For example, adding HBr to 333-trifluoropropene (35) produced the anti-Markovnikov product, 3-bromo-l,l,l-trifluoropropane (36), but only when the reactants were heated in a sealed tube at 100°C with AlBra catalyst (equation 9.28). ... 

Treatment of 3,3-difluorotetrachloropropene with AlBr3 gives, among other products, l-bromo-l,2-dichloro-3,3,3-trifluoropropene (64). The proposed mechanism invokes successive specific attack of soft (Br ) and hard (F ) ions at the softer and harder carbocation centers, respectively. The source of F is from other concurrent processes. 

Ethyl 5-trifluoromethylpyrazole-3-carboxylate was quantitatively prepared in a 1,3-dipolar cycloaddition between ethyl diazoacetate and sulphur (or bromo) derivatives of 3,3,3-trifluoropropene that act as easier to handle synthetic equivalents of 3,3,3-trifluoropropyne [35]. On top of all these studies, the most common strategy for the preparation of 3- and 5-trifluoromethylpyrazoles entails the [3 + 2] heterocy-clization of trifluoromethyl building blocks derived from p-(amino/aIkoxy/thioxy) vinylketones and 1,3-dicarbonyl with monosubstituted hydrazines. Mixtures of regioisomers are often obtained depending on the substrate, the substituent of the hydrazine, and the reaction conditions [36]. 

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