Generating halide

An early report (Briscese and Riveros, 1975) revealed that in the gas phase, alkoxide ions can displace fluoride from fluorobenzene (91). Hydroxide ion fails to react because C6H5F is more acidic than H20 and thus proton transfer becomes the most important channel. Similar reactions with other monohalobenzenes are complicated because these substrates usually generate halide ions directly by dissociative electron attachment. 

In addition to the procedures listed in Table 3.38, further reactions have been used to generate halides upon cleavage. In Section 3.5.2, iodolactonization is presented as a method for the preparation of iodomethyl lactones from resin-bound pentenoic or hexenoic acid derivatives. Closely related to the iodolactonization is the iodine-mediated formation of 2-(iodomethyl)tetrahydrofurans from resin-bound isoxazoli-dines (Entry 9, Table 3.38 for the mechanism, see Figure 15.5). Nitriles can also be prepared by cleavage and simultaneous dehydration of amides RCONH2 from the Rink or Sieber linkers with TFA anhydride (Entry 10, Table 3.38). 

Halogens are electrophilic reagents and can readily cleave many metal alkyls to give the free alkyl halides. One common mechanism involves oxidation of the metal. This increases the electrophilic character of the alkyl group and generates halide ion, so that, paradoxically, it is nucleophilic abstraction of the alkyl group by halide ion that leads to the final products. Co(III) alkyls are known to behave in the same way, and the intermediate Co(IV) species are stable enough to be detected by EPR at -50°C. ... 

Pyrrole synthesis via catalytic dehydrogenation has also received considerable attention. Traditional approaches, such as the Hantzsch and Paal-Knorr pyrrole syntheses, rely on the use of pre-functionalised substrates (Scheme 12.36). In addition, the Hantzsch pyrrole synthesis generates halide waste. 

The reactions of the second class are carried out by the reaction of oxidized forms[l] of alkenes and aromatic compounds (typically their halides) with Pd(0) complexes, and the reactions proceed catalytically. The oxidative addition of alkenyl and aryl halides to Pd(0) generates Pd(II)—C a-hondi (27 and 28), which undergo several further transformations. 

An Q-arylalkanoate is prepared by the reaction of aryl halide or triflate with the ketene silyl acetal 74 as an alkene component. However, the reaction is explained by transmetallation of Ph - Pd—Br with 74 to generate the Pd eno-late 75, which gives the a-arylalkanoate by reductive elimination[76]. 

The 2-substituted 3-acylindoles 579 are prepared by carbonylative cycliza-tion of the 2-alkynyltrifluoroacetanilides 576 with aryl halides or alkenyl tri-flates. The reaction can be understood by the aminopalladation of the alkyne with the acylpalladium intermediate as shown by 577 to generate 578, followed by reductive elimination to give 579[425]. 

The intramolecular insertion of an internal alkyne into an aryl or alkenyl halide 727 generates aryl- or alkenylpalladium as an intermediate, which is trapped with an organozinc or organostannane to give 728. Overall cis addition to the alkyne takes place[595,596]. The reaction of the alkenylstannane 730 with the 2-bromomethylfuran 729 is used for the introduction of a prenyl group[597]. 

Tin enolates of ketones can be generated by the reaction of the enol acetate 733 with tributyltin methoxide[60i] and they react with alkenyl halides via transmetallation to give 734. This reaction offers a useful method for the introduction of an aryl or alkenyl group at the o-carbon of ketones[602]. Tin enolates are also generated by the reaction of siiyl enol ethers with tributyltin fluoride and used for coupling with halides[603]. 

The acylpalladium complex formed from acyl halides undergoes intramolecular alkene insertion. 2,5-Hexadienoyl chloride (894) is converted into phenol in its attempted Rosenmund reduction[759]. The reaction is explained by the oxidative addition, intramolecular alkene insertion to generate 895, and / -elimination. Chloroformate will be a useful compound for the preparation of a, /3-unsaturated esters if its oxidative addition and alkene insertion are possible. An intramolecular version is known, namely homoallylic chloroformates are converted into a-methylene-7-butyrolactones in moderate yields[760]. As another example, the homoallylic chloroformamide 896 is converted into the q-methylene- -butyrolactams 897 and 898[761]. An intermolecular version of alkene insertion into acyl chlorides is known only with bridgehead acid chlorides. Adamantanecarbonyl chloride (899) reacts with acrylonitrile to give the unsaturated ketone 900[762],... 

The carbonylation of some alkyl halides such as iodocyclohexane (911) can be carried out under neutral conditions in the presence of N,N,N.N-tetre,-methylurea (TMU), which is a neutral compound, but catches generated hydrogen halide. Molecular sieves (MS-4A) are used for the same pur-pose[768]. Very reactive ethyl 3-iodobutyrate (912) is carbonylated to give ethyl methylsuccinate (913) in the presence of TMU. The expected elimination of HI to form crotonate, followed by carbonylation, does not occur. 

The reaction of allyl halides with terminal alkynes by use of PdClifFhCNji as a catalyst affords the l-halo-l,4-pentadienes 297. 7r-AlIylpalladium is not an intermediate in this reaction. The reaction proceeds by chloropalladation of the triple bond by PdCh, followed by the insertion of the double bond of the allyl halide to generate 296. The last step is the regeneration by elimination of PdCh, which recycles[148]. The cis addition of allyl chloride to alkynes is supported by formation of the cyclopentenone 299 from the addition product 298 by Ni(CO)4-catalyzed carbonylation[149]. 

These common features suggest that carbocations are key intermediates m alcohol dehydra tions just as they are m the reaction of alcohols with hydrogen halides Figure 5 6 portrays a three step mechanism for the acid catalyzed dehydration of tert butyl alcohol Steps 1 and 2 describe the generation of tert butyl cation by a process similar to that which led to its for matron as an intermediate m the reaction of tert butyl alcohol with hydrogen chloride... 

Carbocations usually generated from an alkyl halide and aluminum chloride attack the aromatic ring to yield alkylbenzenes The arene must be at least as reactive as a halobenzene Carbocation rearrangements can occur especially with primary alkyl hal ides... 

The process in which a dihalocarbene is formed from a tnhalomethane is an ehmi nation m which a proton and a halide are lost from the same carbon It is an a elimination When generated m the presence of an alkene dihalocarbenes undergo cycloaddi tion to the double bond to give dihalocyclopropanes... 

Lithium dialkylamides are excellent bases for making ketone enolates as well Ketone enolates generated m this way can be alkylated with alkyl halides or as illus trated m the following equation treated with an aldehyde or a ketone... 

Phosphoms shows a range of oxidation states from —3 to +5 by virtue of its electronic configuration. Elemental P is oxidized easily by nonmetals such as oxygen, sulfur, and halides to form compounds such as 2 5 2 5 reduced upon reaction with metals to generate phosphides. The... 

Hydrazoyl halides are useful reagents for the synthesis of pyrazolines and pyrazoles (80JHC833). The elimination of HX, usually with triethylamine, is now the preferred method for the generation of the nitrilimine (621) in situ. Although in some cases it is not clear if the mechanism involves a nitrilimine (621) (as for example in the Fusco method in which sodium salts of /3-diketones are used), in other reactions it is the most reasonable possibility. For example, the synthesis of pyrazolobenzoxazine (633) from the hydrazoyl halide (631) probably occurs via the nitrilimine (632). Trifluoromethylpyrazoles (634) have been prepared by the reaction of a hydrazoyl halide and an alkynic compound in the presence of triethylamine (82H(19)179). 

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