Allylic substitutions benzyl amines

Allylic and benzylic amines. The substitution of benzylic and allylic halides proceeds in refluxing THF. The protecting groups on the JV,JV-bis(trimethylsilyl) amines are easily hydrolyzed. 

Aryl alcohol oxidase from the ligninolytic fungus Pleurotus eryngii had a strong preference for benzylic and allylic alcohols, showing activity on phenyl-substituted benzyl, cinnamyl, naphthyl and 2,4-hexadien-l-ol [103,104]. Another aryl alcohol oxidase, vanillyl alcohol oxidase (VAO) from the ascomycete Penicillium simplicissimum catalyzed the oxidation of vanillyl alcohol and the demethylation of 4-(methoxymethyl)phenol to vanillin and 4-hydro-xybenzaldehyde. In addition, VAO also catalyzed deamination of vanillyl amine to vanillin, and hydroxylation and dehydrogenation of 4-alkylphenols. For the oxidation of 4-alkylphenol, the ratio between the alcohol and alkene product depended on the length and bulkiness of the alkyl side-chain [105,106]. 4-Ethylphenol and 4-propylphenol, were mainly converted to (R)-l-(4 -hydroxyphenyl) alcohols, whereas medium-chain 4-alkylphenols such as 4-butylphenol were converted to l-(4 -hydroxyphenyl)alkenes. 

Meisenheimer rearrangement The rearrangement of a tertiary amine oxide on heating to give a substituted hydroxylamine. The migrating group is usually allylic or benzylic. 

Allylic substitution. Allylic carbonates are found to undergo substitution by benzyl-amine, there is regiochemical dependence on solvent ... 

Direct replacement of an amino group by hydrogen is possible only in certain cases. Such reductive fissions are particularly well known for tertiary amines and quaternary ammonium compounds and occur especially readily with allyl- and benzyl-substituted amines. In the last-mentioned cases the benzyl group is removed as toluene, and this reaction route is used for preparation of secondary from primary aliphatic amines the primary amine is first condensed with benzaldehyde, and the resulting Schiff base is reduced to the alkylbenzylamine this is converted by alkylation into the dialkylbenzyl-amine, from which finally the benzyl group is removed by catalytic hydrogenation 544... 

Our current view on the mechanism of the Ir-catalyzed allylic substitution is summarized in Scheme 11.2. The complexes Cl, which are obtained by simply mixing [ Ir(diene)Cl 2] and a phosphoramidite, are catalytically inactive. Catalyst preparation involves activation with a base, which is required in order to generate the cyclometallated complexes C2 (18 valence electrons (VEs)) [3]. An additional base is not required if the nucleophile is sufficiently basic, for example, in case of benzyl or propyl amine. In our laboratory, the non-nucleophilic base TBD (l,5,7-triaz -bicyclo[4.4.0]dec-5-ene) is usually employed because it effects the... 

The Hammett p value of -1-0.36 that was found for the 5 2 allylic substitution reactions between benzyl amine and racemic allyl carbonates substituted with apara-X-Ph- group on C(l) in the presence of a Rh(15,15, 27 ,2R -tangphos)(COD)BF4 catalyst shows that the reaction is aided by electron-withdrawing para-substituents and has a transition state that is more negative than the reactants. A complex multistep mechanism, with two inversions of configuration (an overall retention of configuration), is proposed. The mechanism is further complicated because the two enyl rhodium complexes formed from the two stereoisomers of the racemic allyl carbonates are different and interconvert. 

Intramolecular allylic aminations (Scheme 9.20) proceeded with low catalytic efficiency and with ee-values <90% if procedure (a) (cf. Section 9.2.3.2) was used-that is, the catalyst was not activated [18]. The effect of catalyst activation [procedure (c)] was pronounced [18, 22a] for example, activation with TBD increased the rate of formation of N-benzyl-2-vinylpiperidine by a factor of about 1000. Also notable was the fact that substrate concentration as high as 1M was possible, thereby demonstrating the high preference of intramolecular over intermolecular substitutions leading to oligomers. 

Vinyl substitution occurs with conjugated dienes as well as with alkenes, employing aryl-, vinyl-, methyl-, alkoxycarbonyl- or benzyl-mercury reagents and lithium tetrachloropalladate(II), but the products are usually rr-allylpalladium complexes if the reactions are carried out under mild conditions (equation 8).24,25 The ir-allylic complexes may be decomposed thermally to substituted dienes26 or reacted with nucleophiles to form allylic derivatives of the nucleophile. Secondary amines, for example, react to give tertiary allylic amines in modest yields, along with dienes and reduced dienes (equation 9).25... 

The ease of reduction decreases in the order benzyl > allyl > phenyl > alkyl. Utilizing these differences in reducibility Horner etal. 505 J opened an elegant route to unsymmetrically substituted amines RjR2R3N by combination of alkylation and cathodic cleavage. 

Like other acid chlorides and cyanogen bromide, vinyl chloroformate brings about fission of benzylic and allylic amines e.g. hydrastine is converted into the enol lactone (145).169 Normorphine and norcodeine give substituted thioureas (146) with alkyl isothiocyanates.170... 

Despite the high synthetic value of 1,2-amino alcohols, which are precursors of several therapeutically important sugar fragments, such as daunosamine, vancosamine and ristosamine, the osmylation of allylic amines or their derivatives often occurs with disappointing stereochemical results40 41. (Z)-Substituted allylic carbamates, however, show moderate syn selectivity105. A successful example is illustrated in the synthesis of l-benzyl-3,4-bis(benzyloxy)-5-(l,2-dihy-droxyethyl)pyrrolidine42. 

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