Cp<sub>2</sub>TiCl<sub>2</sub> Catalyzed Debromination of gem-Dibromocyclopropanes to Cyclopropanes by LiBH<sub>4</sub>
Cp2TiCl2 Catalyzed Debromination of gem-Dibromocyclopropanes to Cyclopropanes by LiBH4
Journal of the Korean Chemical Society. 2005. Dec, 49(6): 613-616
Copyright © 2005, The Korean Chemical Society
  • Received : September 27, 2005
  • Published : December 20, 2005
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The reduction of halogen derivatives of hydrocarbons is very efficient and reliable procedure in organic synthesis, and a number of reducing agents for this have been reported. 1 For dehalogenations, gem -dihalocyclopropanes have been shown to be extremely valuable starting materials for the preparation of cyclopropane and cyclopropene derivatives. 2 The reduction of gem -dihalocyclopropanes to monohalocyclopropanes has been effected by various reducing reagents such as organotin hydride, 3a Grignard reagent, 3b chromium sulfate, 3c lithium aluminum hydride, 3d,e sodium borohydride, 3f potassium diphenyl phosphide, 3g sodium hydrogen telluride, 3h and silver perchlorate. 3i Titanium complexes serve as a catalyst for the dehalogenation such as the reduction of aromatic halides with NaBH 4 , 4a,b the dehalogenation of organic halides by RMgX, 4c the defluorination of perfluorodecalin by using Al/HgCl 2 , 4d and the dehalogenation of monohalopyridines with Red-Al. 4e The reductive debromination of vic -dibromides to alkenes by using Cp 2 TiCl 2 /Zn combination reagent 5a or Cp 2 TiCl 2 /In system 5b was also reported. Cp 2 ZrCl 2 has been used for the catalytic dehalogenation of aromatic halides by alkylmagnesium reagents 6a and the stoichiometric hydrolysis of aromatic perfluorocarbons using Mg/HgCl 2 . 6b However, these methods have not been achieved for the direct conversion of gem -dibromocyclopropanes to cyclopropane as a practical method. During the course of our studies on reactions of unsaturated hydrocarbons catalyzed by titanium or zirconium complexes, 7 we found the debromination of gem -dibromocyclopropanes with LiBH 4 to cyclopropanes catalyzed by Cp 2 TiCl 2 in THF (eq. 1 ).
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All glassware used was predried in an oven, assembled hot and cooled with a stream of argon in glove box. All reactions were carried out under argon atmosphere. All solvents were distilled and stored over an appropriate drying agent. Cp 2 TiCl 2 , LiBH 4 , NaBH 4 , and LiAlH 4 were purchased from Strem Co., and used without further purification. Other reagents were purified before use. 1 H NMR spectra were recorded in CCl 4 on Varian Gemini-200 spectrometer with tetramethylsilane as an internal standard. Infrared spectra were measured in a KBr pellet with a Matterson Genesis FT-IR II spectrophotometer. GC analyses were carried out with a Younglin GC-600D gas chromatograph equipped with HP-5 (Hewlett Packard, 0.32 mm, 30 m) capillary columns. Mass spectra were obtained using a Shimadzu GC/MS QP-5050.
Preparation of 1,1-dibromo-2,2-diphenylcyclopropane. A mixture of 1,1-diphenylethene (10.48 g, 58.0 mmol), bromoform (30.33 g, 120.0 mmol), and N,N-dimethyl-n-dodecylamine (0.239 g, 1.12 mmol) was stirred in benzene (15 mL). 50% Sodium hydroxide (80 mL) was added dropwise to the solution, the reaction mixture was stirred vigorously at 50 ℃ for 4 h. The mixture was treated with dilute hydrochloric acid (100 mL) and extracted with diethyl ether/benzene(1/1) (3×30 mL). The organic layer was dried over magnesium sulfate, and the solvent was removed under reduced pressure. Recrystallization of the product from benzene gave 1,1-dibromo-2,2-diphenylcyclopropane (11.3 g, 55%). mp. 154~156 ℃, 1 H NMR (CCl 4 ): δ7.14 ~7.46 (m, 10H, Ar), 2.39 (s. 2H, CH 2 ), IR (cm -1 ): 3029, 1595, 1446, 1162, 669. Mass m/e 350 (M + ), 352 (M + +2), 354 (M + +4).
gem -Dibromocyclopropanes were prepared from appropriate alkenes and dibromocarbene by the reported procedure. 9
Typical procedure for debromination of 1,1-dibromo-2-phenylcyclopropane to phenylcyclopropane. The mixture of Cp 2 TiCl 2 (1.01 g, 4.04 mmol), LiBH 4 (0.894 g, 41.1 mmol), and THF (25 mL) was placed in a vessel under argon. After stirring for 1 h, and 1,1-dibromo-2-phenylcyclopropane (4.40 g, 15.9 mmol) in THF (15 mL) was slowly introduced to the mixture at 40 ℃. The complete reaction was confirmed by GC, and the mixture was treated with dilute hydrochloric acid (20 mL) and extracted with diethyl ether. The organic layer was dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica-gel with n -hexane (1.13 g, 60 %). The distillation of the residue gave phenylcyclopropane under reduced pressure (bp. 62~63℃/13 mm). 1 H NMR (CCl 4 ): δ7.08~7.23 (m, 5H, Ar), 1.70~2.51 (m, 1H, CH), 0.62~1.10 (m, 4H, CH 2 ), IR (cm -1 ): 3028, 1595, 1446, 1162, 729, 699.
The products are already reported (in the literature) and were characterized by comparison with authentic samples using GC and spectral data.
The debromination of 1,1-dibromo-2-phenylcyclopropane ( 1a ) in the presence of catalytic amounts of Cp 2 TiCl 2 was examined in THF under various reaction conditions ( 1 ). In the reaction of 1a (4.1 mmol) with LiBH 4 (10.1 mmol) in THF (15 mL) in the absence of Cp 2 TiCl 2 at 25 ℃ for 5 h, phenyl-cyclopropane ( 2a ) was not obtained and 1a was mostly recovered, but 1-bromo-2-phenylcyclopropane ( 3a ) was obtained in 18% yield at 65 ℃ for 5 h. Addition of catalytic amounts of Cp 2 TiCl 2 (1.1 mmol) to the mixture of 1a and LiBH 4 in THF promoted the debromination of 1a to 2a at 25 ℃, but the reaction proceeded very slowly (48 h). The reaction of 1a occurred smoothly at 40 ℃ for 5 h to give 2a as a major product in an excellent yield, but 2a and 3a were obtained at 65 ℃ for 5 h in 76% and 15% yields, respectively. The reaction of 1a with equimolar amounts of Cp 2 TiCl 2 afforded 2a in 98 % yield without formation of the expected coupling products. 4c The reduction of aryl halides with NaBH 4 catalyzed by Cp 2 TiCl 2 was reported to be solvent dependent. 4b Therefore, we examined the debromination of 1a to 2a with NaBH 4 at 40 ℃ in DMF and diglyme, respectively, but these reactions were not achieved under the same reaction conditions. The reactions required long reaction times or elevated temperatures. 4a,b The similar reduction of 1a with LiAlH 4 instead of LiBH 4 was tested, 2a and 3a were obtained in 76% and 20% yields, respectively. The selectivity of Cp 2 TiCl 2 -LiAlH 4 system shows poorer than that of Cp 2 TiCl 2 -LiBH 4 system for the reduction of gem -dibromocyclopropanes to cyclopropanes. The debromination of gem -dibromocyclopropanes with LiBH 4 catalyzed by Cp 2 TiCl 2 in THF at 40 ℃ was found to be superior and selectively proceeded to give cyclopropanes. The results are listed in 2 . As shown in 2 , the debromination of gem -dibromocyclopropanes with phenyl groups ( 1a~1c ) occurred to give the corresponding cyclopropanes in an excellent yields, but the yields of cyclopropanes with p -tolyl and alkyl groups ( 1d , 1e ) were low and monobromocyclopropanes ( 3d , 3e ) were little obtained with recovery of the substrates in high yields. The product yields are considerably affected by the electronic nature of substituents on the gem -dibromocyclopropanes. The reduction of trans - 1c was achieved to give trans - 2c . The debromination of 1g and 1h smoothly proceeded without a cleavage of C-O bond. The debrominations are chemoselective as ether and ester groups remained unaffected under the reaction conditions. 5b , 6a Also, the dechlorination of 1,1-dichloro- 2,2-diphenylcyclopropane was applied to this reagent system. This reaction hardly occurred under the same conditions, and required a elevated temperature (65 ℃) and a longer time to complete the reaction (>48 h). 4a Deuterolysis after the reaction of 1b with LiBH 4 did not give any trace of deuterated 1,1-diphenylcyclopropanes, but the reaction of 1b with LiBD 4 gave dideuterated 1,1-diphenylcyclopropane. The source of hydrogen in this reaction should be derived from LiBH 4 . The reaction mechanism is not clear yet. However, we would like to consider possible paths on Cp 2 TiCl 2 catalyzed debromination of gem -dibromocyclopropanes by LiBH 4 . One involves a oxidative addittion/reductive elimination to the low valence titanium complex species. 6 Another possible path is a radical reaction involving reduced titanium complex catalysts. 4b Although the role of Cp 2 TiCl 2 is still not clarified, it is likely that reduction of Cp 2 TiCl 2 (IV) with LiBH 4 provides low valent titanium, which reacts with gem -dibromocyclopro-panes to give cyclopropanes. 9 The actual reaction might be further complicated with multiple paths. Although the scope and limitations were not fully established, the present method could be a practical alternative to conventional method.
Debromination of1acatalyzed by Cp2TiCl2under various conditionsa
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aCatalyst: reducing agent : 1a = 1 : 10 : 4. bGC yields.
Debromination ofgem-dibromocyclopropanesa
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aCp2TiCl2 : LiBH4 : substrate = 1 : 10 : 4, 40 ℃, 5 h. bGC yields, isolated yields in parenthesis. cTrans type.
Hudlický M. 1984 Reductions in Organic Chemistry; Ellis Horwood Chichester England 62 - 69
Masakzu Y. , Rikisaku S. 1991 Terahedron Lett. 32 3349 -    DOI : 10.1016/S0040-4039(00)92703-5
Sayferth. D. , Yamazaki H. , Alleston D. L. 1963 J. Org. Chem. 28 703 -    DOI : 10.1021/jo01038a025
Meunier B. 1981 J. Organomet. Chem. 204 345 -    DOI : 10.1016/S0022-328X(00)80503-3
Davies S. G. , Thomas S. E. 1984 Synthesis 1027 -    DOI : 10.1055/s-1984-31062
Hara. R. , Sun W-H. , Nishihara Y. , Takahashi T. 1997 Chem. Lett. 1251 -    DOI : 10.1246/cl.1997.1251
Isagawa K. , Sano H. , Hattori M. , Otsuji Y. 1979 Chem. Lett. 1069 -    DOI : 10.1246/cl.1979.1069
Kadlec V. , Kadlecová H. , Štrouf O. 1974 J. Organomet. Chem. 82 113 -    DOI : 10.1016/S0022-328X(00)80726-3
Dohmlow E. V. , Schönefeld J. 1971 Liebigs Ann. Chem. 744 42 -    DOI : 10.1002/jlac.19717440108