Allyl bromide bromination

Synthesis of (A) started with the combination of 2,4,6-trimethylphenol and allyl bromide to give the or/Ao-allyl dienone. Acid-catalyzed rearrangement and oxidative bydroboration yielded the dienone with a propanol group in porlactone ring were irons in the product as expected (see p. 275). Treatment with aqueous potassium hydroxide gave the epoxy acid, which formed a crystalline salt with (R)-l-(or-naphthyl)ethylamine. This was recrystallized to constant rotation. 

An asymmetric synthesis of estrone begins with an asymmetric Michael addition of lithium enolate (178) to the scalemic sulfoxide (179). Direct treatment of the cmde Michael adduct with y /i7-chloroperbenzoic acid to oxidize the sulfoxide to a sulfone, followed by reductive removal of the bromine affords (180, X = a and PH R = H) in over 90% yield. Similarly to the conversion of (175) to (176), base-catalyzed epimerization of (180) produces an 85% isolated yield of (181, X = /5H R = H). C8 and C14 of (181) have the same relative and absolute stereochemistry as that of the naturally occurring steroids. Methylation of (181) provides (182). A (CH2)2CuLi-induced reductive cleavage of sulfone (182) followed by stereoselective alkylation of the resultant enolate with an allyl bromide yields (183). Ozonolysis of (183) produces (184) (wherein the aldehydric oxygen is by isopropyUdene) in 68% yield. Compound (184) is the optically active form of Ziegler s intermediate (176), and is converted to (+)-estrone in 6.3% overall yield and >95% enantiomeric excess (200). 

Allylation of the 7-hydroxyquinoline derivative 242 with allyl bromide gave the corresponding 7-allyl ether 243 which underwent Claisen rearrangement to give the 8-allyl derivative 244. Acylation and subsequent bromination afforded the dibromopropyl derivative 245. Treatment of 245 with KOH/EtOH gave 8-hydroxypyrroloquinoline 246 that was methylated with methyl iodide to afford 247 (91JOC980) (Scheme 44). 

Bromination of the diphenyl indole derivative 316 with bromine in DMF or trimethylammonium bromide afforded the 7-bromo derivative 317. Reaction with allyl bromide or its derivatives gave A-allyl derivatives 318 that upon cyclization with palladium acetate gave 7,9-dimethoxy-l,2-diphenylpyrrolo[3,2,l-// ]quinoline derivatives 319 (92T7601) (Scheme 57). 

Olefins react with bromine by addition of the latter to the carbon-carbon double bond. In contrast the Wohl-Ziegler bromination reaction using N-bromosuccinimide (NBS) permits the selective substitution of an allylic hydrogen of an olefinic substrate 1 by a bromine atom to yield an allylic bromide 2. 

The chain propagation step consists of a reaction of allylic radical 3 with a bromine molecule to give the allylic bromide 2 and a bromine radical. The intermediate allylic radical 3 is stabilized by delocalization of the unpaired electron due to resonance (see below). A similar stabilizing effect due to resonance is also possible for benzylic radicals a benzylic bromination of appropriately substituted aromatic substrates is therefore possible, and proceeds in good yields. 

Allylic bromides can also serve as progenitors for nucleophilic organochromium reagents. An elegant example is found in Still and Mobilio s synthesis of the 14-membered cembranoid asperdiol (4) (see Scheme 2).7 In the key step, reduction of the carbon-bromine bond in 2 with chromium(n) chloride in THF is attended by intramolecular carbonyl addition, affording a 4 1 mixture of cembranoid diastereoisomers in favor of the desired isomer 3. Reductive cleav-... 

The group ofWalborsky probably has described one of the first true anionic/radi-cal domino process in their synthesis of the spirocyclopropyl ether 2-733 starting from the tertiary allylic bromide 2-730 (Scheme 2.161) [369]. The first step is a Michael addition with methoxide which led to the malonate anion 2-731. It follows a displacement of the tertiary bromide and a subsequent ring closure which is thought to involve a SET from the anionic center to the carbon-bromine anti bonding orbital to produce the diradical 2-732 and a bromide anion. An obvious alternative Sn2 halide displacement was excluded due to steric reasons and the ease with which the reaction proceeded. 

Allylic bromination of 235 with excess CuBr and PhCCb-f-Bu (1 1 molar ratio) gives the separable allylic bromides 236 and 237 with 62% and 15% yield, respectively. Further treating the allylic bromide 236 with CuBr in CH3CN at 50° C leads to a mixture of 236 and 237, from which 25% of 236 and 69% of 237 can be separated. 

Addition of the dicyanomethyl radical to propadiene (la) occurs exclusively at Q (not shown in Scheme 11.8) [60]. On the other hand, methyl-substituted allenes, e.g. Id, undergo /3-selective reactions with 2-bromomalodinitrile (15). The significant /3-selectivity has been associated with the steric demand of the incoming radical 16, which favors addition to the sterically least hindered site at the diene Id to provide allylic radical 17. However, it seems likely that a stabilization of an intermediate allylic radical, e.g. 17, by methyl substituents contributes significantly to the observed regioselectivity of product formation. Trapping of intermediate 17 with bromine atom donor 15 proceeds at the least substituted carbon to afford allylic bromide 18. 

Dibromopropan-l-ol has been prepared by reaction of allyl alcohol, bromine, and aqueous lithium bromide (Jenkner Rabe, 1967 Thomas Levek, 1972). 

Ethylene Dichloride Allyl Bromide Beryllium Oxide Bromine... 

When bromine, iodine, or allyl bromide electrophiles were used, 3-methyl-2-methoxypyridine (290) was isolated, a result that can be explained by a fast exchange between the RX reagent and MeLi followed by reaction of the resulting MeX with the 3-lithio species 288 (Scheme 87). 

Knoevenagel condensation of aldehydes with 1,3-dicarbonyl compounds and subsequent NBS bromination yields allylic bromides, which are converted thermally to 3-acyl- or 3-alkoxycarbonyl furans (Scheme 51) (78JOC4596). 

In a 3-I. round-bottom flask, a hydrobromic add solution is made by the sulfur dioxide reduction of 480 g. of bromine in the presence of 510 g. of ice water or a mixture is made of 1000 g. of aqueous 48 per cent hydrobromic acid and 300 g. of concentrated su. furic acid. To this are added 385 cc. of aqueous allyl alcohol, which, according to bromine titration, contain 233 g. of pure allyl alcohol. The 3-I. round-bottom flask is fitted with a mechanical stirrer (Fig. 1, p. 4, see also Notes), separatory funnel, and an efficient condenser set for downward distillation. Stirring is started and 300 g. of concentrated sulfuric add are added gradually through the separatory funnel to the warm solution. The allyl bromide distils over completely in about one-half to one hour. The crude allyl bromide is washed with dilute sodium carbonate solution, is dried over calcium chloride and is distilled. The yield of product boiling at 60-72° from a number of experiments varies from 443 to 465 g. (92-96 per cent theory). A small high-boiling fraction is also obtained and examination has shown this to consist of propylene bromide. 

To determine the purity of any sample of allyl alcohol, 1 cc. is run into 15 to 25 cc. of carbon tetrachloride and this solution is then treated in the cold with a carbon tetrachloride solution of bromine (standardized with potassium iodide and sodium thiosulfate) until a permanent bromine coloration is obtained. The amount of allyl alcohol present in any solution may also be determined roughly by conversion to allyl bromide. From several experiments it was found that the allyl bromide obtained was equivalent to the amount of allyl alcohol as determined by bromine titration. 

Exercise 14-3 The reaction of W-bromosuccinimide (NBS) with alkenes to produce allylic bromides is thought to involve molecular bromine produced by the reaction... 

The early stage of electrophilic bromination of tetraisobutylethylene (TTBE) has been examined to detect the formation constant (K[) for the 1 1 charge-transfer complex (in CH2CI2, AcOH and MeOH). Based on the Kf values, the thermodynamic parameters for CTC formation from TTBE + Br2 are AH = —4.2( 0.2) kcalmol-1 and AS = —9.5( 0.7) e.u. TTBE reacts with Br2 to afford substitution products, two of which are an initially formed allylic bromide and a more slowly formed diene bromide127. 

The addition of bromine usually proceeds the most smoothly, and is conveniently carried out in a solvent such as carbon tetrachloride. The examples of the addition of bromine to allyl bromide and the addition of bromine to undec-10-enoic acid are illustrative (Expts 5.67 and 5.23). 

Allylic bromination normally uses NBS as bromine itself would add to the alkene. Thus cyclohexene gives the dibromide 18 with Br2 but the allylic bromide with NBS. Bromine radicals abstract one of the marked H atoms from 19 and the intermediate allylic radical 21 is delocalised so we don t know which end of the allylic system5 ends up attached to Br. 

The reaction of 83 with NaH and allyl bromide afforded 86. In this product, the double bonds are distant from the ring by a CH2 group, so 86 underwent a typical alkene reaction, for example bromination, affording 87 (Scheme 9) <1996CB161>. 

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