Hypervalent iodine-promoted aminobromination of electron-deficient olefins with Bromamine-T

A convenient and practical procedure for the aminobromination of electron-deficient olefins using Bromamine-T as nitrogen and bromine source promoted by (diacetoxyiodo)benzene has been developed. This metal-free protocol is highly efficient and affords the vicinal bromamines with excellent stereoselectivities


Introduction
The vicinal haloamine functionalities represent valuable synthetic intermediates of various pharmacologically active compounds and can be transformed into other useful structures via substitution reactions of the halogen atom with a wide range of nucleophiles. 1 Typically, these compounds can be obtained from the aminohalogenation of carbon-carbon double bonds.In this context, various systems employing N-halo nitrogen derivatives 2 or the combination of nitrogen source and NBS 3 have been developed. 4Recently, palladium salts 5 and Lewis acids 6 catalyzed aminohalogenation processes have also been reported, giving the vicinal haloamines with high yield and stereoselectivity.
However, the aminohalogenation of electron-deficient olefins remains relatively rare probably due to the low activity of the reaction site.Very recently, elegant work focused on the copper and palladium catalyzed aminochlorination reactions have revealed that various electrondeficient olefins including α,β-unsaturated esters, 7 ketones, 8 amide, 9 nitriles, 10 and nitrostyrenes 11 can be aminochlorinated with high efficiency. 12On the other hand, as green chemistry becomes a crucial concern in modern synthetic chemistry, avoiding metal catalysis in chemical process is highly desirable.Delightedly, Li and coworkers reported a metal-free aminochlorination reaction of chalcones in ionic liquid. 13At almost the same time, we discovered that the aminohalogenation of electron-deficient olefins can be promoted by (diacetoxyiodo)benzene [PhI(OAc) 2 ] 14 or Brønsted acids 15 with Chloramine-T 16 or the combination of TsNH 2 and NBS as nitrogen and halogen sources.As an analogue of Chloramine-T, Bromamine-T has been mainly utilized as a titrant in oxidimetric estimations 17 and occasionally as an oxidant. 18ecently, a few papers have described the employment of Bromamine-T as nitrene surrogate for the aziridination of olefins 19a-g and the amidation of benzylic C-H bonds.19b,h However, using Bromamine-T as both nitrogen and bromine sources simultaneously still remains unexplored.Herein we demonstrate the aminobromination of electron-deficient olefins with Bromamine-T promoted by PhI(OAc) 2 .

Results and Discussion
We embarked on the study of solvent and temperature effects in a test reaction of chalcone 1a with Bromamine-T (2.0 equiv) by the action of PhI(OAc) 2 .The results are summarized in Table 1.At 25 o C, the reaction was very sluggish in CH 2 Cl 2 and furnished the product in low yield after 5 hours, remaining lots of chalcone 1a uncharged (entry 1).Elevating the reaction temperature proved helpful and the bromamine 3a was able to be isolated in 74% yield within 1.5 hour (entry 2).The hydrogen atom required in this transformation was believed to come from the atmosphere moisture.Further efforts to reduce the loading of PhI(OAc) 2 and Bromamine-T were unsuccessful; the yields dropped notablely even though the reaction time was prolonged (entries 3-4).The reaction performed in 1,2-dichloroethane (DCE) was disadvantageous; only give the product in 31% yield (entry 5).CH 3 CN, which was used as a privileged solvent in aminohalogenation reactions, 12 afforded 3a in 25% yield (entry 6).Other common solvents were also screened; however all of them exhibited negative activity towards this aminobromination process (entries 7-13).After a brief screening of the solvent, the use of CH 2 Cl 2 was found to be optimal to attain high conversion and the substrate generality was investigated next (Table 2).It was obvious to see that irrespective of the substituent pattern and the electronic property of the aryl moiety, the products could be obtained in good yields with very good diastereoselectivities when chalcones were employed as reactants (entries 1-8).The chalcone 1i was an exception since the strong electron withdrawing group influenced the activity of the double bond obviously.The final product was isolated in moderate yield as a single diastereomer (entry 9).Furthermore, other electron-deficient double bond systems were also examined.Enone with methyl substituent on the carbonyl side was feasible, affording the bromamine 3j in 57% yield along with high diastereoselectivity (entry 10).To our delight, the cinnamate and cinnamide were also tolerable in the present system; both of them gave the corresponding products in moderate yields as anticonfiguration exclusively (entries 11-12).Bromamine-T was found to be an ideal nitrene source in the transition metal catalyzed aziridination of olefins.19b Further exploration of our aminobromination reaction revealed that when chalcone 1b, Bromamine-T, and PhI(OAc) 2 was mixed in refluxing CH 2 Cl 2 for 1.5 h, bromamine 3b was isolated in 72% yield along with 5% yield of aziridine 4 (Scheme 1).It has been reported that a significant amount of bromamine product was obtained in the palladium catalyzed aziridination of electron-deficient olefins which was believed to be generated by the subsequent nucleophilic ring opening of the corresponding aziridine with bromine ion.19c,g To understand how the bromamine was produced in our system, extra investigation was made.We found that the yield of aziridine increased considerably when the reaction time was prolonged to 4 hours (Scheme 1).However, this conversion stopped at about 31% yield of aziridine 4 after 9 hours.Accordingly, we believed that the aziridine observed in our system was generated from the bromamine by losing hydrobromide in the presence of base 7e,20 which was released during the aminobromination process. 14,15Actually, when excessive NaOH was added directly after the reaction mixture was refluxed in CH 2 Cl 2 for 1.5 h, the bromamine 3b disappeared and aziridine 4 was obtained in 65% yield after another 0.5 h (Scheme 2).This finding supported our hypothesis adequately.

Conclusions
In conclusion, we have discovered Bromamine-T to be an efficient nitrogen and bromine source in the hypervalent iodine-promoted aminobromination of electron-deficient olefins.The reactions, which are characterized by their operational ease and high efficiency, lead to diastereoselective vicinal bromamine formation, proceed well for α,β-unsaturated ketones, cinnamate, and cinnamide.

Experimental Section
General procedure for the aminobromination of electron-deficient olefins with Bromamine-T promoted by PhI(OAc) 2 To a mixture of olefin 1 (0.2 mmol), Bromamine-T (0.4 mmol, 108.8 mg), and (diacetoxyiodo)benzene (0.1 mmol, 32.3 mg) in a 25 mL round-bottom flask was added CH 2 Cl 2 (2 mL).This suspension was heated to reflux for the indicated time monitored by TLC.After the disappearance of the starting material, the resulting mixture was filtrated and the filtrate was separated on a silica gel column with petroleum ether/ethyl acetate 5/1 as the eluent to get the desired product 3.
Procedure for the aziridination of enone 1b with Bromamine-T To a mixture of enone 1b (0.2 mmol, 48.5 mg), Bromamine-T (0.4 mmol, 108.8 mg), and (diacetoxyiodo)benzene (0.1 mmol, 32.3 mg) in a 25 mL round-bottom flask was added CH 2 Cl 2 (2 mL).This suspension was heated to reflux for 1.5 h.Then NaOH (0.6 mmol, 24.0 mg) was added directly to the reaction mixture and the stirring was continued for another 0.5 h (monitored by TLC).After the disappearance of the bromamine 3b, the resulting mixture was filtrated and the filtrate was separated on a silica gel column with petroleum ether/ethyl acetate 4/1 as the eluent to get the desired product 4 (53.5 mg, 65% yield).
All products reported here have previously been isolated and fully characterized, and were confirmed by comparison of their spectral data with the reported data.

Table 1 .
Continued 2 (0.1 mmol) in the indicated solvent.b Isolated yields by flash column chromatography.c Determined by the analysis of 1 H NMR. d 0.06 mmol of PhI(OAc) 2 was employed.e 0.3 mmol of Bromamine-T was employed.f Not determined.

Table 2 .
Continued a Unless otherwise specified, all reactions were performed with olefin 1 (0.2 mmol), Bromamine-T (0.4 mmol), and PhI(OAc) 2 (0.1 mmol) in refluxing CH 2 Cl 2 .b Isolated yields by flash column chromatography.c Determined by the analysis of 1 H NMR. d 0.6 mmol of Bromamine-T was employed.