Journal Information
Journal ID (publisher-id): chemical
Title: Journal of the Korean Chemical Society
Translated Title (ko): 대한화학회지
ISSN (print): 1017-2548
ISSN (electronic): 2234-8530
Publisher: Korean Chemical Society대한화학회
INTRODUCTION▼
The protection and deprotection of double bonds via bromination-debromination strategy can conveniently be utilized in organic synthesis.1 Although debromination reactions of vic-dibromides effected by various reagents have been reported previously, many of these methods suffer from one or more drawbacks such as low yields, long reaction times, poor chemoselectivity, and harsh reaction conditions.2 As a consequence, there has been a search for the development of new improved methods for this conversion.
The chemical reactivity of VCl3/Zn system has been the subject of considerable interest and the reducing ability of this system has been extensively studied.3 Low-valent vanadium reagents generated from vanadium(III) chloride and zinc serve as versatile one-electron reductant, but their synthetic utility in this respect has been limited. One-electron reduction has synthetic potential for the generation of radical intermediates. It has been reported that VCl3/Zn system can be used as a reagent for the stereoselective debromination of gem-dibromocyclopropanes.4 We considered that VCl3/In system could be a protocol for the debromination of vic-dibromides. To the best of our knowledge, there is no report in which VCl3/In system is used as a reagent for reductive debromination of vic-dibromides to alkenes. The reaction can be generalized as shown by Scheme 1.
Over the past several decades, indium metal has attracted great interest in organic synthesis owing to its intriguing properties.5 As in the case of zinc, the reduction potential of indium is not too negative (Eo(In3+/In) = -0.345 V; Eo, (Zn2+/Zn) = -0.763 V) and thus it is not only stable in the air, but also practically inert in water. Moreover, indium metal apparently has no significant toxicity.6 As a part of our ongoing research program to explore highly efficient low valent metal for useful organic transformations.7 we report here a rapid and efficient procedure for debromination of vic-dibromides to the corresponding alkenes with VCl3/In system.
EXPERIMENTAL▼
General
All commercial reagents were purchased from Aldrich and Fluka Chemical Company and used without any further purification. NMR spectra were recorded on a FT-Bruker AF-300 (300 MHz for 1H NMR; 75 MHz for 13C NMR) in CDCl3 using TMS as an internal standard. Mass spectra were recorded on a Shimadzu GC MS-QP 1000 PX at 70 eV. TLC analysis was performed on silica gel plates (Merck, 60 F-254). All products were purified by flash column chromatography using silica gel 60 (79-230 mesh, Merck).
General Procedure for the Reaction
A 10-mL round-bottomed flask was charged with indium powder (230 mg, 2.0 mmol), vanadium trichloride (157 mg, 1.0 mmol) and THF (4 mL). The resulting mixture was stirred for 30 min under sonication producing a solution of the low-valent vanadium-indium complex. 1,2-Dibromo-1,2-diphenylethane (170 mg, 0.5 mmol) was then added to this solution and the reaction mixture was stirred for 3 min at room temperature. The progress of the reaction was monitored by TLC. After completion of the reaction, the solvent was removed under reduced pressure and the residue was then extracted with ethyl acetate (3 × 10 mL). The combined extract was washed with brine, dried over anhydrous Na2SO4 and concentrated. The crude product was further purified by column chromatography on a silica gel (hexane:ethyl acetate = 10:1) to provide trans-stilbene (85 mg, 94%). All the products were identified by comparison of their spectroscopic data with authentic compounds.
Spectroscopic Data of Products
4-Chlorostyrene (Entry 1): 1H NMR (300 MHz, CDCl3): δ 7.24-7.34 (m, 4H), 6.64 (dd, 1H, J = 17.6, 11.1 Hz), 5.71 (d, 1H, J = 17.8 Hz), 5.25 (d, 1H, J = 11.1 Hz). 13C NMR (75 MHz, CDCl3): δ 136.0, 135.6, 133.4, 128.6, 127.4, 114.4. GC/MS (m/z): 138 (M+), 140 (M+2).
4-Bromostyrene (Entry 2): 1H NMR (300 MHz, CDCl3): δ 7.45 (d, 2H, J = 9.6 Hz), 7.23 (d, 2H, J = 9.6 Hz), 6.63 (dd, 1H, J = 17.6, 11.1 Hz), 5.71 (d, 1H, J = 17.6 Hz), 5.25 (d, 1H, J = 11.1 Hz). 13C NMR (75 MHz, CDCl3): δ 136.4, 135.7, 131.6, 127.7, 121.5, 114.5. GC/MS (m/z): 183 (M+), 185 (M+2).
4-Fluorostyrene (Entry 3): 1H NMR (300 MHz, CDCl3): δ 7.40-7.35 (m, 2H), 7.04-6.98 (m, 2H), 6.68 (dd, 1H, J = 17.7, 11.1 Hz), 5.66 (d, 1H, J = 17.7 Hz), 5.22 (d, 1H, J = 10.8 Hz). 13C NMR (75 MHz, CDCl3): δ 164.1, 135.7, 133.8, 127.8, 115.5, 113.4. GC/MS (m/z): 122 (M+)
trans-Stilbene (Entry 4): 1H NMR (300 MHz, CDCl3): δ 7.23-7.54 (m, 10H), 7.06 (s, 2H). 13C NMR (75 MHz, CDCl3): δ 137.3, 128.6, 128.5, 127.5, 126.4. GC/MS (m/z): 180 (M+)
4-Allylanisole (Entry 5): 1H NMR (300 MHz, CDCl3): δ 7.08 (d, 2H, J = 8.4 Hz), 6.82 (d, 2H, J = 8.4 Hz), 6.00-5.86 (m, 1H), 5.06-5.01 (m, 2H), 3.77 (s, 3H). 3.31 (d, 2H, J = 6.9 Hz). 13C NMR (75 MHz, CDCl3): δ 157.9, 137.8, 132.0, 129.4, 115.3, 113.8, 55.2, 39.2. GC/MS (m/z): 148 (M+).
Indene (Entry 6): 1H NMR (300 MHz, CDCl3): δ 7.18-7.51 (m, 4H), 6.89-6.92 (m, 1H), 6.56-6.59 (m, 1H), 3.42 (s, 2H). 13C NMR (75 MHz, CDCl3): δ 144.7, 143.5, 134.0, 131.9, 126.0, 124.4, 123.6, 120.8, 39.0. GC/MS (m/z): 116 (M+)
4-Acetoxystyrene (Entry 7): 1H NMR (300 MHz, CDCl3): δ 7.42 (d, 2H, J = 8.7 Hz), 7.05 (d, 2H, J = 8.7 Hz), 6.71(dd, 1H, J = 17.4, 11.1 Hz), 5.72 (d, 1H, J = 17.4 Hz), 5.25 (d, 1H, J = 11.1 Hz), 2.30 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 169.3, 150.1, 135.8, 135.2, 127.1, 121.6, 113.9, 21.1. GC/MS (m/z): 162 (M+).
5-Dibenzosuberenone (Entry 8): 1H NMR (300 MHz, CDCl3): δ 7.51-8.23 (m, 8H), 7.26 (s, 2H). 13C NMR (75 MHz, CDCl3): δ 182.5, 138.1, 132.3, 130.8, 129.7, 128.0, 127.6, 127.0. GC/MS (m/z): 206 (M+).
trans-Chalcone (Entry 9): 1H NMR (300 MHz, CDCl3): δ 8.05 (d, 1H, J = 8.7 Hz), 7.41-7.83 (m, 11H). 13C NMR (75 MHz, CDCl3): δ 190.4, 144.7, 138.0, 134.8, 132.7, 130.4, 128.8, 128.5, 128.4, 128.3, 122.0. GC/MS (m/z): 208 (M+).
Methyl trans-cinnamate (Entry 10): 1H NMR (300 MHz, CD3OD): δ 7.70 (d, 1H, J = 15.1 Hz), 7.36-7.54 (m, 5H), 6.42 (d, 1H, J = 15.1 Hz), 3.81 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 167.3, 144.7, 134.2, 130.2, 128.8, 127.9, 117.7, 51.7. GC/MS (m/z): 162 (M+).
trans-4-Phenyl-3-buten-2-one (Entry 11): 1H NMR (300 MHz, CDCl3): δ 7.38-7.56 (m, 6H), 6.72 (d, 1H, J = 16.2 Hz), 2.39 (s, 3H), 13C NMR (75 MHz, CDCl3): δ 198.2, 143.3, 134.2, 130.4, 128.9, 128.1, 127.0, 27.5. GC/MS (m/z): 146 (M+).
trans-Cinnamic acid (Entry 12): 1H NMR (300 MHz, CD3OD): δ 11.18 (br, 1H), 7.82 (d, 1H, J = 15.3 Hz), 7.15-7.68 (m, 5H), 6.53 (d, 1H, J = 15.3 Hz). 13C NMR (75 MHz, CDCl3): δ 172.7, 147.0, 133.9, 130.7, 128.9, 128.3, 117.2. GC/MS (m/z): 148 (M+).
RESULTS AND DISCUSSION▼
The new reducing system was readily generated by the addition of indium powder to a solution of vanadium (III) chloride in tetrahydrofuran (THF) under sonication.8 Treatment of vic-dibromides with VCl3/In system at room temperature resulted in formation of the corresponding alkenes in high yields within a short period of time. To optimize the reaction condition, the amounts of VCl3 and indium were varied and the optimum molar ratio of VCl3 to indium (1:2) was found to be suitable in terms of yield and reaction time. With the optimized reaction conditions in hand, functionally and structurally diverse vic-dibromides as substrates for debromination were examined in an effort to elucidate the scope and limitations of this reaction. The representative results are summarized in Table 1.
The functional group tolerance of this method is evident from Table 1 which showed that chloro, bromo, fluoro, keto, ester, carboxyl, and methoxy groups are unaffected under the reaction conditions. It is worthwhile to note that the sensitive carbonyl group remains intact without reduction of C=O bond (entries 7-12). Significantly, only trans-ole-fins are observed and there is no chance of overreduction of the C=C bond formed in this process.9 A control experiment revealed that the reaction was not initiated at all without VCl3. Thus, a combination of indium and vanadium (III) chloride is essential to carry out the debromination. In comparison with other procedures, the VCl3/indium system reduced vic-dibromides more rapidly (3-10 min) in higher yields (88-95%) with a good chemoselectivity.
Table1.
Reductive debromination of vic-dibromides with VCl3/indium system
aThe products were characterized by comparison of their spectral data with authentic samples. bIsolated yields.
Although the detailed mechanism of the reaction requires more investigation, a low-valent vanadium species generated in situ by treatment with indium is likely to be involved in a single electron transfer (SET) process. The reaction is believed to proceed via the formation of a relatively stable radical intermediate, which directly collapses to give the alkene. It may be proposed that the presence of an aryl substitution is beneficial to the preferential radical formation at the carbon adjacent to radical stabilizing group and therefore to the reaction rate as well. The notable advantages offered by this method are mild reaction conditions, short reaction time, high yields, no overreduction of double bonds, and tolerance to various sensitive moieties.
CONCLUSION▼
In conclusion, we have developed an improved method for the debromination of vic-dibromides with VCl3/indium system. The mildness and rapidity as well as high yields make the present method highly practical for debromination of various vic-dibromides. Further investigations for the more useful applications with the system are currently in progress.