Triflates bromination

To investigate the feasibility of employing 3-oxidopyridinium betaines as stabilized 1,3-dipoles in an intramolecular dipolar cycloaddition to construct the hetisine alkaloid core (Scheme 1.8, 77 78), a series of model cycloaddition substrates were prepared. In the first (Scheme 1.9a), an ene-nitrile substrate (i.e., 83) was selected as an activated dipolarophile functionality. Nitrile 66 was subjected to reduction with DIBAL-H, affording aldehyde 79 in 79 % yield. This was followed by reductive amination of aldehyde x with furfurylamine (80) to afford the furan amine 81 in 80 % yield. The ene-nitrile was then readily accessed via palladium-catalyzed cyanation of the enol triflate with KCN, 18-crown-6, and Pd(PPh3)4 in refluxing benzene to provide ene-nitrile 82 in 75 % yield. Finally, bromine-mediated aza-Achmatowicz reaction [44] of 82 then delivered oxidopyridinium betaine 83 in 65 % yield. 

To avoid the retro-Diels-Alder reaction, 56 was dihydroxylated prior to the introduction of the bromine atom (57). Removal of the acetonide group followed by cleavage of the diol afforded a bis-hemiacetal. Selective reduction of the less-hindered hemiacetal group gave 58. The remaining hemiacetal was protected, and the ketone was converted to an enol triflate, thus concluding the synthesis of the electrophilic coupling component 51. 

Analogously, 5-tributylstannylimidazole 29 was easily obtained from the regioselective deprotonation of 1,2-disubstituted imidazole 28 at C(5) followed by treatment with tributyltin chloride [24]. In the presence of 2.6 equivalents of LiCl, the Stille reaction of 29 with aryl triflate 30 afforded the desired 1,2,5-trisubstituted imidazole 31 with 2,6-di-tert-butyl-4-methylphenol (BHT) as a radical scavenger. Reversal of the nucleophile and electrophile of the Stille reaction also provided satisfactory results. For example, the coupling reaction of 5-bromoimidazole 33, derived from imidazole 32 via a regioselective bromination at C(5), and vinylstannane 34 produced adduct 35 [24],... 

Buynak et al. reported the synthesis of representative 7-vinylidenecephalosporine derivatives bearing an axial allene chirality (Scheme 4.5) [9]. A chiral allene 24 was prepared stereoselectively utilizing the reaction of an organocopper reagent with propargyl triflate 23, obtained by a diastereoselective ethynylation of the ketone 22 with ethynylmagnesium bromide. Terminally unsubstituted allene 26 was synthesized via bromination of the triflate 23 followed by reduction of the bromide 25 with a zinc-copper couple. 

Telluride 34 was treated with triflic anhydride in the presence of 1 equivalent of DMSO in dichloromethane at room temperature to give Te-(trifluor-omethyl)dibenzotellurophenium triflate (35). Triflate 35 was also synthesized by treating 34 with bromine in l,l,2-trichloroethane at room temperature followed by triflic acid at reflux temperature. Triflate 35 was converted to bromide 36 by treatment with tetrabutylammonium bromide... 

Silver ion makes possible in the second reaction an isnmeri/ation-free hydrolysis of the S,0 acetal to ketone 32. Generation of the cnol triflate 33 is accomplished in the third step with the Hendrickson-Me M it rry reagent (Tf2NPh).10 Addition of an alcohol produces the potassium aikoxide, which because of its lower basicity permits isomerization to the thermodynamically favored enolate. Chemose-lective reaction to bromohydnn 9 is achieved in the last step with NBS as brominating agent in aqueous THF. NBS acts here as a source of cationic bromine in an ionic mechanism. The intermediate bromonium ion forms preferentially at a) electron-rich double bonds and h) the sterieally least hindered double bond. It also opens in such a way as to provide the most stable carbocation. 

The synthesis of chlorine (I) and bromine (I) trifluoromethanesulfonates (triflates) was reported by DesMarteau. Stability and reactivity of these materials are similar to those of perfluoroalkyl hypohalites. Both compounds readily react at low temperature with a variety of fluoroolefins. Based on NMR analysis of the products of adding CF3S020X to pure cis- or trans-isomers of 1, 2-difluoroethylene, it was concluded that the reaction proceeds as syn-addition [35]. This statement was later criticized [18], since the assignment of stereoisomers was found to be incorrect. According to [18], addition of CF3S020X to haloolefins, as well as reactions of ClF, BrF and IF proceed as anti-addition via cyclic halonium cationic intermediates. 

Both chlorine and bromine triflates react with HFP to give only one, Markovnikov type, additional product, which is yet further evidence of the electrophilic mechanism of the process, since radical addition of CF3OF to F-propene produces a mixture of two regio isomers [35] ... 

Under similar conditions, chlorine and bromine triflates add to olefin 9 ... 

Substrates with several sp2-bound triflate groups, bromine or iodine atoms, respectively, may sometimes undergo several Heck reactions in a row. A threefold Heck reaction of 1,3,5-tribromobenzene with styrene is shown in Figure 16.37. 

Vinyllithiums cf. 13, 142).10 An improved route to vinyllithiums involves coupling of vinyl and aryl triflates with tributyl- or trimethylstannylcuprates of the formula (R3Sn)2Cu(CN)Li2, prepared from LDA, R,SnH, and CuCN in THF at -50° to -60°. The higher-order cuprates couple with vinyl and aryl triflates at -20° to provide a vinyltin intermediate. Work-up of the intermediate with AgOAc provides a vinyltin, with bromine a vinyl bromide, or with CF,COOH an aryltin. 

The chlorine atom in 142b and 144c may be replaced with bromine or triflate group to give 149 or 150 by the reaction with the appropriate MesSiX (X = Br , OTf ) reagent (equation 37). These substitutions proceed under mild conditions, which is a result of a... 

Unsaturated amides are easily converted to imidates by 0-alky la ting reagents such as trimethyl-oxonium telrafluoroborate or trimethylsilyl triflate. Nucleophilic attack by the thus formed imino group on an halonium ion followed by hydrolysis gives a lactam. Thus an unsaturated dimethyl imidate was treated with bromine in dichloromethane at 0 °C and cyclized with total regio- and stereoselectivity to give 1, since the tertiary cation forces the cyclization towards the formation of a six-membered ring. The trans addition to the double bond was shown by successive conversion to a m-aziridine 2126. 

The hydrolytically and thermally stable, crystalline camphor-derived isoselenazolidine 5 was prepared by treatment of the diselenide 96 with bromine and silver triflate (Scheme 33) <1997JA2079>. 

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