Hydrobromination of Alkenes with PBr 3 / SiO 2 : a Simple and Efficient Regiospecific Preparation of Alkyl Bromides

Surface mediated reactions are of great utility in organic synthesis, and in many cases the products are obtained in better yields and improved selectivities than in a homogeneous media in solution. The reagents or catalysts can be supported or unsupported in these reactions. Organic halides are important compounds in organic synthesis, where functional group interconversions mediated by substitution reactions (radical or ionic) are of great utility. HBr adds readily to most alkenes predominantly with Markovnikov regioselectivity. However, unless the substrate is rigorously purified (alkenes readily absorb oxygen from the air) and the reaction media is isolated from light and air to avoid formation of small amounts of peroxides, competing radical-chain addition to give the anti-Markovnikov products occurs. As the generation and transfer of the hygroscopic gas HBr is inconvenient and difficult to perform stoichiometrically, alternate methodologies for performing hydrobromination of alkenes are of great interest. Kropp and co-workers showed that oxalyl bromide or bromotrimethylsilane undergo hydrolysis on the surface of silica gel to generate HBr in situ, which produces alkyl or alkenyl bromides in high yields via highly Markovnikov additions to carbon-carbon double or triple bonds. This methodology has the advantage of not requiring anhydrous conditions nor generation of toxic and corrosive gaseous HBr. Surprisingly, although Kropp studied the reaction of (COBr) 2 and Me 3 SiBr/SiO 2 with 1-octene only, no study was done with PBr 3 . This latter reagent is easily available and cheaper than the previous ones and also more efficient in terms of the stoichiometry of the reaction, as only one mol equiv. of PBr 3 would generate 3 mol equiv. of HBr in its reaction with water (Scheme 1). Furthermore, PBr 3 is more useful in terms of atom economy than (COBr) 2 and Me 3 SiBr.


Introduction
Surface mediated reactions are of great utility in organic synthesis, and in many cases the products are obtained in better yields and improved selectivities than in a homogeneous media in solution [1][2][3] .The reagents or catalysts can be supported [1][2][3] or unsupported in these reactions 4 .
Organic halides are important compounds in organic synthesis, where functional group interconversions mediated by substitution reactions (radical or ionic) are of great utility 5 .HBr adds readily to most alkenes predominantly with Markovnikov regioselectivity 6,7 .However, unless the substrate is rigorously purified (alkenes readily absorb oxygen from the air) and the reaction media is isolated from light and air to avoid formation of small amounts of peroxides, competing radical-chain addition to give the anti-Markovnikov products occurs 8 .As the generation and transfer of the hygroscopic gas HBr is inconvenient and difficult to perform stoichiometrically 6,7 , alternate methodologies for performing hydrobromination of alkenes are of great interest.
Kropp and co-workers showed that oxalyl bromide or bromotrimethylsilane undergo hydrolysis on the surface of silica gel to generate HBr in situ 7 , which produces alkyl or alkenyl bromides in high yields via highly Markovnikov additions to carbon-carbon double or triple bonds 6 .This methodology has the advantage of not requiring anhydrous conditions nor generation of toxic and corrosive gaseous HBr.
Surprisingly, although Kropp studied the reaction of (COBr) 2 and Me 3 SiBr/SiO 2 with 1-octene only 7 , no study was done with PBr 3 .This latter reagent is easily available and cheaper than the previous ones 9 and also more efficient in terms of the stoichiometry of the reaction, as only one mol equiv. of PBr 3 would generate 3 mol equiv. of HBr in its reaction with water (Scheme 1).Furthermore, PBr 3 is more useful in terms of atom economy 10 than (COBr) 2 and Me 3 SiBr.
In previous communications we showed that the hydrohalogenation of (R)-limonene with SOCl 2 /SiO 2 11 and Scheme 1.
PBr 3 /SiO 2 12 produces chemo-and regiospecifically the respective a-terpinyl halides.Now we studied the scope of the hydrobromination of alkenes with PBr 3 /SiO 2 and communicate our results.

Results and Discussion
The reaction of styrene (10 mmol) with PBr 3 (0.4 mol equiv.) was studied in the presence of SiO 2 (5 g) in CH 2 Cl 2 in an open flask at room temperature (rt).The reaction led to a quantitative yield of 1-bromo-1-phenylethane, with purity greater than 99% (by HRGC-High Resolution Gas Chromatography) in only 20 min.A control experiment was also made in the absence of SiO 2 where 1 mol equiv. of water was added to the reaction media.The results indicate that the presence of SiO 2 is really important, as in its absence the reaction was not complete in the same reaction time (88%, crude yield).
Based on the above results we made a systematic study of the reaction of diverse alkenes and 0.4 mol equiv. of PBr 3 /SiO 2 and the results are shown in Scheme 2 and Table .In all cases only the Markovnikov addition products were obtained and no trace of the regioisomeric anti-Markovnikov bromides were detected using all analytical techniques (HRGC, 1 H and 13 C NMR).The alkyl bromides were obtained in 50 -79% isolated yield (> 95 -99% purity by HRGC) and were characterised by physical 13 and spectroscopic data.
Interestingly, under similar conditions, isoprene at -8 o C underwent exclusively 1,4-addition to afford the corresponding monobromide in 54% isolated yield and greater than 99% purity by HRGC.The reaction time was considerably shorter than the reported literature method, which takes 5 h or more to give the product 14 .Oncemore, there is no need of anhydrous conditions nor generating dry gaseous HBr as reported 14 .
In summary, the reaction of alkenes with PBr 3 /SiO 2 in CH 2 Cl 2 is an easy and efficient way to prepare alkyl  bromides with Markovnikov regiospecificity.Furthermore, our methodology avoids the need of drying chemicals, rigorous exclusion of moisture, light, and oxygen from the reaction media, and manipulation/generation of dry toxic and corrosive gaseous HBr.

Experimental
Isoprene was distilled prior to use, and the other alkenes were used as received.SiO 2 (Aldrich, 270-70 MESH, 60 Å) was used as received 15 , PBr 3 (Merck), and other chemicals were also used as received. 1H and 13 C NMR were acquired on a Bruker AC-200 (200 MHz and 50 MHz, respectively) spectrometer in CDCl 3 solutions with TMS as internal standard.IR spectra were recorded on a Perkin-Elmer 1600 FT-IR spectrometer (KBr film).Analyses by HRGC were performed on a HP-5890-II gas chromatograph with FID by using a 28 m (length), 0.25 mm (ID) and 0.50 mm (phase thickness) RTX-5 silica capillary column and H 2 (flow rate 50 cm s -1 ) as carrier gas (split 1:10).Oven temp.:

General procedure for the preparation of alkyl bromides
To a stirred suspension of the appropriated alkene (10 mmol) and SiO 2 (5 g) in CH 2 Cl 2 (25 cm 3 ), a solution of PBr 3 (4 mmol) in CH 2 Cl 2 (10 cm 3 ) was added for 10 min at rt.After completed addition, the suspension was stirred for several minutes (see Table ) and then filtered.The SiO 2 was washed with CH 2 Cl 2 (15 cm 3 ), the combined liquid was washed with 10% NaHCO 3 (until no more gas was liberated), brine (2 x) and the organic extract was dried (Na 2 SO 4 ).The solvent was evaporated in a rotatory evaporator at reduced pressure to give the pure alkyl bromide.
70 o C then 8 o C/min to 300 o C, injector temp.: 260 o C, detector temp.: 280 o C.

Table .
Alkyl bromides from the reaction of alkenes with PBr 3 / SiO 2 in CH 2 Cl 2 .