Alkenes from ammonium salts

The preparation of an alkene 3 from an amine 1 by application of a /3-elimination reaction is an important method in organic chemistry. A common procedure is the Hofmann elimination where the amine is first converted into a quaternary ammonium salt by exhaustive methylation. Another route for the conversion of amines to alkenes is offered by the Cope elimination. 

The metal-catalysed autoxidation of alkenes to produce ketones (Wacker reaction) is promoted by the presence of quaternary ammonium salts [14]. For example, using copper(II) chloride and palladium(II) chloride in benzene in the presence of cetyltrimethylammonium bromide, 1-decene is converted into 2-decanone (73%), 1,7-octadiene into 2,7-octadione (77%) and vinylcyclohexane into cyclo-hexylethanone (22%). Benzyltriethylammonium chloride and tetra-n-butylammo-nium hydrogen sulphate are ineffective catalysts. It has been suggested that the process is not micellar, although the catalysts have the characteristics of those which produce micelles. The Wacker reaction is also catalysed by rhodium and ruthenium salts in the presence of a quaternary ammonium salt. Generally, however, the yields are lower than those obtained using the palladium catalyst and, frequently, several oxidation products are obtained from each reaction [15]. 

Chiral solvomercuration was accomplished by carrying out the reaction of alkenes with Hg(OAc)2 in the presence of chiral quaternary ammonium salts synthesized from natural ephedrine.642 Chiral secondary alcohols may be isolated with ee values up to 96%. Chiral nitrogen-containing diselenides are transformed by perox-odisulfate to selenium electrophiles, which may add to alkenes to form oxyseleny-lation products. These are, however, not isolated but oxidized to induce oxidative p-hydride elimination to afford chiral allyl methyl ethers with ee values up to 75%.643... 

Dichlorocarbene addition to aikenes. Dehmiow and LisseP have examined the reaction variables in the generation of dichlorocarbene by PTC. Optimal conditions include use of 4 molar excess each of CHCI3 and 50% aqueous NaOH, 1 mole % of catalyst, and efficient stirring. The reaction should be conducted initially at 0-5°, then at 20° for 1-2 hours, and finally at 50° for 2-4 hours. Most quaternary ammonium salts are suitable as catalysts the anions should be chloride or hydrogen sulfate. From the point of cost/efficiency, the most useful are benzyltriethylammonium chloride, tetra-n-butylammonium chloride, Aliquat 336, and tri-n-propylamine. The reaction rate is strongly dependent on the nucleophilicity of the alkene. 

C-Alkylation of the sodio derivative is accomplished by a technique similar to the alkylation of malonic ester. Primary halogen compounds, quaternary ammonium salts,and an alkene oxide have been used as alkylating agents. Alkylation by secondary halides has been less successful. Hydrolysis of the substituted esters to acetylated amino acids is described for leucine (64%) and phenylalanine (83%). Hydrolysis with deacylation has been used to prepare histidine (45%) and phenylalanine (67%). Glutamic acid (75%) is obtained from substituted acylaminomalonates prepared by the Michael condensation of methyl acrylate and the acylated amino esters. ... 

Apart from the reactions of diazonium salts, a number of other reactions are known in which the C-N bond is broken. The best known of these is the Hofmann elimination of quaternary ammonium hydroxides (Scheme 2.37). An amine is converted by methylation with methyl iodide to the quaternary ammonium salt ( exhaustive methylation ). The iodide, on treatment with moist silver oxide, forms the quaternary ammonium hydroxide which undergoes a bimolecular elimination to form an alkene. The bimolecular elimination of onium salts yields the least alkylated alkene. This substitution pattern is determined by the ease with which a hydrogen atom can be attacked by the base. 

A Pyrrolidine is a secondary amine and reacts with two moles of methyl iodide to form a quaternary ammonium salt, compound A. The analytical data for compound B shows that it has one double bond equivalent which is present as an alkene. Consequently, compound B has been formed from compound A by a Hofmann elimination ... 

When the ammonium salt is heated in Step [3], OH removes a proton from the P carbon atom, forming the new k bond of the alkene. The mechanism of elimination is E2, so ... 

What is the stereochemistry of the alkene formed from the Hofmann elimination of each quaternary ammonium salt H... 

In E2 elimination with bases like KOH and CH30Na, most alkyl halides give Saytzeflf orientation. Certain other compounds (quaternary ammonium salts, Sec. 23.5, for example) give Hofmann orientation. Alkyl sulfonates fall in between. With each kind of compound, orientation is affected—sometimes drastically—by the choice of base and solvent, and by stereochemistry. (The percentage of 1-hexene from 2-hexyl chloride, for example, jumps from 33% in CH ONa/ CH3OH to 91% in /-BuOK//-BuOH, evidently for steric reasons.) In all this, we should remember that orientation is a matter of relative stabilities of competing transition states these stabilities are determined by electronic factors—alkene character and carbanion character—with superimposed conformational factors. 

The synthesis of stereodefined acyclic alkenes via 3-elimination reactions—such as (1) dehydration of alcohols, (2) base-induced eliminations of alkyl halides or sulfonates (tosyl or mesyl esters), and (3) Hofmann eliminations of quaternary ammonium salts—often suffers from a lack of regio- and stereoselectivity, producing mixtures of isomeric alkenes. 

Alkenes from Quaternary Ammonium Salts Alkenes from p-Toluenesulfonylhydrazones... 

The general reaction for obtaining alkenes from quaternary ammonium salts is shown in Scheme 25. 

Hofmann elimination Formation of alkenes from quaternary ammonium salts. 206... 

The synthesis of 1,1-diiodocyclopropane is carried out via addition of diiodocarbene (car-benoid) to alkenes the carbene, in turn, is generated from iodoform and a base. The process is realized using phase-transfer catalysis,(33% or 50%aqueous sodium hydroxide and a quaternary ammonium salt, typically benzyltriethylammonium chloride, as a catalyst) or in the presence of potassium ter/-butoxide in /ert-butyl alcohol 25,127,128 g... 

Allyl amines in the form of their ammonium salts can be used as substrates for palladium(O)-catalyzed alkylations. They are particularly interesting because they are easily obtained optically pure from amino acids. (S)-l-Isobutenyl-2-(Z)-butenyl trimethyl ammonium iodide yields with high regioselectivity the (5)-( )-alkene 55. The C-N chirality is almost completely transferred to the newly formed C —C bond. The double-bond geometry and the configuration of the stereocenter is simultaneously inverted, thus the reaction proceeds under net retention of configuration via a syn-syn-n allylpalladium complex, which is formed by n-a-n rearrangement123. 

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