Stereochemistry Hofmann elimination

Name the following amine, including R,S stereochemistry, and draw the product of its reaction with excess iodomethane followed by heating with Ag20 (Hofmann elimination). Is the stereochemistry of the alkene product Z or E Explain. 

For eliminations, form the carbon-carbon double bond according to Zaitsev s rule (except the Hofmann elimination) and use anti elimination to determine the stereochemistry of E2 reactions. 

Cope elimination occurs under milder conditions than Hofmann elimination. It is particularly useful when a sensitive or reactive alkene must be synthesized by the elimination of an amine. Because the Cope elimination involves a cyclic transition state, it occurs with syn stereochemistry. 

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

The stereochemistry of Hofmann elimination is commonly anti but less so than was formerly believed. Syn elimination is important for certain cyclic compounds, and can be made important even for open-chain compounds by the proper choice of base and solvent. Quaternary ammonium ions are more prone to syn elimination than alkyl halides and sulfonates. Electronically, anti formation of the double bond is favored in eliminations but when the alkene character of the transition state is slight—as here—other factors come into play conformational factors, it has been postulated. 

Coke, J. L. Stereochemistry of Hofmann eliminations. Selective Organic Transformations 1972, 2, 269-307. 

Burch, R. R., Manring, L. E. N-Alkylation and Hofmann elimination from thermal decomposition of R4N salts of aromatic polyamide polyanions synthesis and stereochemistry of N-alkylated aromatic polyamides. Macromolecules 99, 24, 1731-1735. 

The key to this problem is to understand that Hofmann elimination occurs via an E2 mechanism requiring anti coplanar stereochemistry, whereas Cope elimination requires syn coplanar stereochemistry. 

Note that a syn orientation refers to the mechanism of elimination and not the stereochemistry of the subsequently formed alkene. A syn elimination can result in a trans product, as was shown earlier. The Cope elimination differs from the Hofmann elimination of quaternary ammonium salts which is a trans elimination. 

Unlike what happens in other E2 reactions, the major product of the Hofmann elimination is the less highly substituted alkene rather than the more highly substituted one, as shown by the reaction of (1-methylbutyl)-trimethylammonium hydroxide to give pent-l-ene rather than the alternative pent-2-ene. The reason for this non-Zaitsev stereochemistry is probably steric. Because of the large size of the trialkylamine leaving group, the base must abstract a hydrogen from the most accessible, least hindered position. 

Sometimes referred to as the Hofmann Degradation. This elimination reaction of alkyl trimethyl amines proceeds with anti-stereochemistry, and is generally suitable for producing alkenes with one or two substituents. The reaction follows the Hofmann Rule. 

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. 

Sicher, J., Svoboda, M., Pankova, M., Zavada, J. Stereochemistry. LXII. Hofmann-Saytzeff and the syn-anti elimination dichotomy. Relation between the two phenomena. Collect. Czech. Chem. Commun. 1971,36, 3633-3649. 

The Saytzev s Rule and Hofmann s Rule can be used to predict the orientation of elimination, and the stereochemistry is preferentially antiperiplanar. 

Neostrychnine. Neither the Hofmann, Emde, or cyanogen bromide reactions have been particularly useful as starting points for systematic degradations of strychnine because of the stereochemistry which is not suitable for eliminations and instead a multiplicity of Sn2 products were usually formed. It was a study of the Hofmann degradation that first led to neostrychnine (Chart 6.4), a double bond isomer (J20,2i Qf strychnine, a compound more readily made by heating strychnine with selenium or Raney... 

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