2- Bromo-3-methyl-2 -butene, reaction

Other allyl metal complexes can be used to generate carbon bonds, including allyl zinc complexes. Stille showed that 3-methyl-l-bromo-2-butene reacted with zinc chloride (ZnCl2) to generate the it-allyl zinc species. Coupling required the use of an organotin species such as a-trimethyltin isoprene (466). Reaction in refluxing THF led to a 94% yield of myrcene (467).303... 

In Chapter 7 we discussed how haloalkanes (or alkyl sulfonates) in the presence of strong base can nndergo elimination of the elements of HX with simultaneons formation of a carbon-carbon donble bond. With many substrates, removal of a hydrogen can take place from more than one carbon atom in a molecule, giving rise to constitutional (donble-bond) isomers. In snch cases, can we control which hydrogen is removed—that is, the regio-selectivity of the reaction (Section 9-9) The answer is yes, to a limited extent. A simple example is the elimination of hydrogen bromide from 2-bromo-2-methylbutane. Reaction with sodinm ethoxide in hot ethanol fnmishes mainly 2-methyl-2-butene, but also some 2-methyl-1 -butene. 

Bromination of isoprene using Br2 at —5 ° C in chloroform yields only /n j -l,4-dibromo-2-methyl-2-butene (59). Dry hydrogen chloride reacts with one-third excess of isoprene at —15 ° C to form the 1,2-addition product, 2-chloro-2-methyl-3-butene (60). When an equimolar amount of HCl is used, the principal product is the 1,4-addition product, l-chloro-3-methyl-2-butene (61). The mechanism of addition is essentially all 1,2 with a subsequent isomerization step which is catalyzed by HCl and is responsible for the formation of the 1,4-product (60). The 3,4-product, 3-bromo-2-methyl-1-butene, is obtained by the reaction of isoprene with 50% HBr in the presence of cuprous bromide (59). Isoprene reacts with the reactive halogen of 3-chlorocyclopentene (62). 

Ketones such as methyl cyclohexyl ketone 1284 react with DMSO/TCS 14, via their enol form, to give 21% of the chloroketone 1285 a and 63% of the a-methyl mercaptoketone 1286 [70]. Reaction of 1284 with DMSO/MesSiBr (TBS) 16 affords 85% of the bromo compound 1285 b and 12% hexahydrophenacyl bromide 1287 but no 1286 [71]. Whereas reaction of tra s-4-phenyl-3-buten-2-one (benzalacetone) 1288 with DMSO/TCS 14 gives 81% of the sulfonium salt 1289 [70], the y9-dicar-bonyl compound ethyl acetoacetate furnishes 69% of 1290 [70]. In contrast with DMSO/TCS 14, the combination DMSO/TBS 16 effects selective monobromina-tion of y9-dicarbonyl compounds [71] (Scheme 8.28). 

Somei and co-workers made extensive use of the Heck reaction with haloindoles in their synthetic approaches to ergot and other alkaloids [26, 40, 41, 240-249]. Thus, 4-bromo-l-carbomethoxyindole (69%) [26], 7-iodoindole (91%) (but not 7-iodoindoline or l-acetyl-7-iodoindoline) [40, 41], and l-acetyl-5-iodoindoline (96%) [41] underwent coupling with methyl acrylate under standard conditions (PdlOAc /PhsP/EtjN/DMF/100 °C) to give the corresponding (E)-indolylacrylates in the yields indicated. The Heck coupling of methyl acrylate with thallated indoles and indolines is productive in some cases [41, 241, 246]. For example, reaction of (3-formylindol-4-yl)thallium bis-trifluoroacetate (186) affords acrylate 219 in excellent yield [241], Similarly, this one-pot thallation-palladation operation from 3-formylindole and methyl vinyl ketone was used to synthesize 4-(3-formylindol-4-yl)-3-buten-2-one (86% yield). 

Somei adapted this chemistry to syntheses of (+)-norchanoclavine-I, ( )-chanoclavine-I, ( )-isochanoclavine-I, ( )-agroclavine, and related indoles [243-245, 248]. Extension of this Heck reaction to 7-iodoindoline and 2-methyl-3-buten-2-ol led to a synthesis of the alkaloid annonidine A [247]. In contrast to the uneventful Heck chemistry of allylic alcohols with 4-haloindoles, reaction of thallated indole 186 with 2-methyl-4-trimethylsilyl-3-butyn-2-ol affords an unusual l-oxa-2-sila-3-cyclopentene indole product [249]. Hegedus was also an early pioneer in exploring Heck reactions of haloindoles [250-252], Thus, reaction of 4-bromo-l-(4-toluenesulfonyl)indole (11) under Heck conditions affords 4-substituted indoles 222 [250], Murakami described the same reaction with ethyl acrylate [83], and 2-iodo-5-(and 7-) azaindoles undergo a Heck reaction with methyl acrylate [19]. 

Hegedus synthesis of ( )-clavicipitic acid //-acetyl methyl ester culminated in the Pd-induced cyclization of 238 to 239, the latter of which was reduced to the target mixture [251], Substrate 238 was prepared via a Heck reaction with the corresponding 4-bromo compound 223 and 2-methyl-3-buten-2-ol (83%). The cyclization also occurs with tosic acid (97%). 

The results of the olefin oxidation catalyzed by 19, 57, and 59-62 are summarized in Tables VI-VIII. Table VI shows that linear terminal olefins are selectively oxidized to 2-ketones, whereas cyclic olefins (cyclohexene and norbomene) are selectively oxidized to epoxides. Cyclopentene shows exceptional behavior, it is oxidized exclusively to cyclopentanone without any production of epoxypentane. This exception would be brought about by the more restrained and planar pen-tene ring, compared with other larger cyclic nonplanar olefins in Table VI, but the exact reason is not yet known. Linear inner olefin, 2-octene, is oxidized to both 2- and 3-octanones. 2-Methyl-2-butene is oxidized to 3-methyl-2-butanone, while ethyl vinyl ether is oxidized to acetaldehyde and ethyl alcohol. These products were identified by NMR, but could not be quantitatively determined because of the existence of overlapping small peaks in the GC chart. The last reaction corresponds to oxidative hydrolysis of ethyl vinyl ether. Those olefins having bulky (a-methylstyrene, j8-methylstyrene, and allylbenzene) or electon-withdrawing substituents (1-bromo-l-propene, 1-chloro-l-pro-pene, fumalonitrile, acrylonitrile, and methylacrylate) are not oxidized. 

The stability of dialkylimidazolium cation-containing ionic liquids can be a problem even at moderate temperatures in the presence of some reagents or catalysts. For example, when CsF and KF were used in the ionic liquid [BMIM]PFg to perform a halogen exchange reaction in an attempt to replace Br from bromo-carbons with F , it was found that alkyl elimination from the [BMIM] cation took place, forming methyl imidazole, 1-butene, 1-fluorobutane, and other unidentified products at 150°C overnight 69). The fluoride ion acted as a base that promotes elimination or substitution processes. 

As a result of an extensive study, it has been found that methylene groups are attacked much more readily than a methyl group. For example, 2-methyl-2-butene requires 16 hours for completion of the reaction, whereas, 2-methyl-2-hexene requites 10 minutes. The conversion of cyclohexene to 3-broraocyclohexene is accomplished in 20 minutes in 87% yield. It is noteworthy that the bromination of 1-octene with N-btomo-succinimide yields a mixture of l-bromo-2-octene and 3-bromo-1-octene and that the proportion of these isomers is in close agreement with the equilibrium mixture formed at 100° by analogous bromides. ... 

The procedure has been extended to the formation of difunctional compounds like 3-methyl-3-butenal diethyl acetal (24%), 1,1-diethoxy-2-butyne (80%), and /3-ethoxyethyl methyl ketone diethyl ketal (92%). A somewhat related reaction is the formation of diethyl acetals of a-formyl esters by treatment of a-bromo esters with zinc and ethyl ortho formate (45 60%). ... 

This selective metalation has been used for the synthesis of several bisabolane sesquiterpenes. Thus the sesquiterpene (- )-J -bisabolene (7) can be synthesized in one step from metalated ( —)-limonene by reaction with I-bromo-3-methyl-2-butene. Two... 

The synthesis of the nonsteroidal anti-inflammatory drug nabumetone (9) was developed by Hoechst-Celanese [71]. It was prepared via a Heck coupling of 2-bromo-6-methoxy-naphthalene (1) with methyl vinyl ketone in the presence of palladium catalyst [71]. Further reduction of unsaturated ketone provided 9. Nabumetone was also obtained in a one-step coupling reaction of 2-bromo-6-methoxy-naphthalene with 3-buten-2-ol followed by isomerization of enol [72]. 

The iV-isopentenyl derivatives of dendroxine and of 6-hydroxy-dendroxine were isolated as chlorides from these plants. The latter was prepared by the reaction of l-bromo-3-methyl-2-butene with... 

The neuroexcitatory amino acid a-kainic acid, a popular testing ground for new pyrrolidine syntheses, has been prepared by a number of routes that involve free-radical cyclization reactions. Bachi has reported two approaches that involve iminoyl radical cyclizations. One enantioselective route is described in Scheme 6 [35]. Isonitrile 48 was prepared in 4 steps from 4-bromo-3-methyl-2-butenal dimethyl acetal, the key reaction being an enantioselective addition of tert-butyl oc-isocyanoacetate to an aldehyde mediated by Hiyashi s catalyst. Treatment of 48 with a catalytic... 

Some electrophilic addition reactions give products that are clearly not the result of the addition of an electrophile to the sp carbon bonded to the greater number of hydrogens and the addition of a nucleophile to the other sp carbon. For example, the addition of HBr to 3-methyl-1-butene forms 2-bromo-3-methylbutane (minor product) and 2-bromo-2-methylbutane (major product). 2-Bromo-3-methylbutane is the product you would expect from the addition of H to the sp carbon bonded to the greater number of hydrogens and Br to the other sp carbon. 2-Bromo-2-methylbutane is an unexpected product, even though it is the major product of the reaction. 

If the conjugated diene is not symmetrical, the major products of the reaction are those obtained by adding the electrophile to whichever terminal sp carbon results in formation of the more stable carbocation. For example, in the reaction of 2-methyl-l,3-butadiene with HBr, the proton adds preferentially to C-1 because the positive charge on the resulting carbocation is shared by a tertiary allylic and a primary allylic carbon. Adding the proton to C-4 would form a carbocation with the positive charge shared by a secondary allylic and a primary allylic carbon. Because addition to C-1 forms the more stable carbocation, 3-bromo-3-methyl-l-butene and l-bromo-3-methyl-2-butene are the major products of the reaction. 

A typical reaction that illustrates Markovnikov addition is the reaction of HBr with 2-methyl-2-butene to give 2-bromo-2-methylbutane (1, sec. 2.10.A). This reaction proceeds by formation of the more stable carbo-cation, which reacts with the nucleophilic bromide ion. If the anti-Markovnikov bromide (the bromine resides on the less substituted carbon) is desired, a different mechanistic pathway must be followed. A typical anti-Markovnikov addition reaction is addition of borane to the alkene, giving primary alcohol (2) after oxidation of the intermediate alkylborane (sec. 5.4.A). This alcohol can be converted to the anti-Markovnikov bromide, 3, by treatment with PBr3. The key to controlling such reactions is a fundamental... 

The reaction of aryllithiums with l-bromo-2-methyl-3-buten-2-ol in the presence of Pd(PPh3)4 is a rare example of the use of alkyl halides in Pd-catalyzed cross-coupling (Scheme 62). The required oxidative addition step must be assisted by the homoallylic double bond and/or /3-OH group. The absence of a /3-H atom in the allylic position must also be critically responsible for the observed success. 

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