Amine reaction with enones

The net effect of the Stork reaction is the Michael addition of a ketone to an cn/3-unsaturated carbonyl compound. For example, cyclohexanone reacts with the. cyclic amine pyrrolidine to yield an enamine further reaction with an enone such as 3-buten-2-one yields a Michael adduct and aqueous hydrolysis completes the sequence to provide a 1,5-diketone (Figure 23.8). 

A typical second step after the insertion of CO into aryl or alkenyl-Pd(II) compounds is the addition to alkenes [148]. However, allenes can also be used (as shown in the following examples) where a it-allyl-r 3-Pd-complex is formed as an intermediate which undergoes a nucleophilic substitution. Thus, Alper and coworkers [148], as well as Grigg and coworkers [149], described a Pd-catalyzed transformation of o-iodophenols and o-iodoanilines with allenes in the presence of CO. Reaction of 6/1-310 or 6/1-311 with 6/1-312 in the presence of Pd° under a CO atmosphere (1 atm) led to the chromanones 6/1-314 and quinolones 6/1-315, respectively, via the Jt-allyl-r 3-Pd-complex 6/1-313 (Scheme 6/1.82). The enones obtained can be transformed by a Michael addition with amines, followed by reduction to give y-amino alcohols. Quinolones and chromanones are of interest due to their pronounced biological activity as antibacterials [150], antifungals [151] and neurotrophic factors [152]. 

Michael reaction with exocycHc ,(S-enones Conjugate addition of secondary amines to a,/ -enones proceeds readily unless the enonc is cxocyclic. in "Such a case the reaction is very slow unless alumina is added as catalyst. Thus the reaction of 1 and diethylamine in the presence of alumina proceeds in 2 hours to give 2 quantitatively. 

Another important function of protecting groups is to prevent a reagent from attacking itself. In the last chapter, when we discussed the synthesis of the bicyclic amine monomorine, we used the protected enone 12 but did not say how it was made. The chloroketone 9 is first made1 in 89-93% yield from the ketolactone 6 simply by reaction with HC1. Chloride displaces the protonated ester group 7 and the product 8 decarboxylates under the conditions of the reaction. 

Tertiary amines have also been employed in electron transfer reactions with a variety of different acceptors, including enones, aromatic hydrocarbons, cyanoaro-matics, and stilbene derivatives. These reactions also provide convincing evidence for the intermediacy of aminoalkyl radicals. For example, the photoinduced electron transfer reactions of aromatic hydrocarbons, viz. naphthalene, with tertiary amines result in the reduction of the hydrocarbon as well as reductive coupling [183, 184]. Vinyl-dialkylamines can be envisaged as the complementary dehydrogenation products their formation was confirmed by CIDNP experiments [185]. 

Imagine a cyclic p-fluoro-enone reacting with a secondary amine in a conjugate substitution reaction. The normal addition to form the enolate followed by return of the negative charge to expel the fluoride ion gives the product. 

Tfce preferred synthetic route to these important intermediates is the Mannich reaction (Chapter 27), The compound is stored as the stable Mannich base and the unstable enone released by elimination of a tertiary amine with mild base, The same conditions are right for this elimination and for conjugate addition, Thus the aw-methylene compounds can be formed in the flask for immediate reaction with the enol(ate) nucleophile, The overall reaction from (3-amino carbonyl to 1,5-dicarbonyl appears to be a substitution but the actual mechanism involves elimination and conjugate addition,... 

Enones react with benzofuroxan in the presence of a primary or secondary amine to afford specific quinoxaline monoxides the course of the reaction depends on the nature of the base. The usefulness of these reactions for synthesis are limited by low yields and the lack of universality for enones as substrates. 

The nucleophilic capture of the trichlorocyclopropenium ion is not restricted to aromatics. In fact treatment of tetrachlorocyclopropene with secondary amines and thiols results in tris-amino- and thio- cyclopropenium ions, e.g. 76. One advantage of such species is in their reaction with nucleophiles, e.g. HO", which deliver the corresponding sp -hybridized derivative, e.g. enone 77, by an addition-elimination sequence The transammination reaction, initially performed in good-to-excellent yields with secondary amines, often employs a trimethylsilylamine which has allowed for the synthesis of the tris-(mono-organylamino)cyclopropenium salt (76a) in almost quantitative yield. 

Reaction of 2,3-diphenylcyclopropenone tosylhydrazone with amines in dichloromethane at 20°C gave l-amino-2,3-diphenylprop-2-enone tosylhydrazones 5. ... 

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