Enones coupling with amines

Sha et al. (45) reported an intramolecular cycloaddition of an alkyl azide with an enone in an approach to a cephalotaxine analogue (Scheme 9.45). Treatment of the bromide 205 with NaN3 in refluxing methanol enabled the isolation of compounds 213 and 214 in 24 and 63% yields, respectively. The azide intermediate 206 underwent 1,3-dipolar cycloaddition to produce the unstable triazoline 207. On thermolysis of 207 coupled with rearrangement and extrusion of nitrogen, compounds 213 and 214 were formed. The lactam 214 was subsequently converted to the tert-butoxycarbonyl (t-Boc)-protected sprrocyclic amine 215. The exocyclic double bond in compound 215 was cleaved by ozonolysis to give the spirocyclic ketone 216, which was used for the synthesis of the cephalotaxine analogue 217. 

Lewis acid promoted reactions of silicon enolates, /.e., silyl enol ethers and ketene silyl acetals with various electrophiles have yielded a wealth of novel and selective synthetic methods. This combination of reagents has been used in the past to perform such reactions as aldol-condensations with aldehydes and acetals, imine-condensations, conjugate additions to a,P-enones, alkylations, electrophilic aminations, and Diels-Alder/cyclocondensations. Our own interest in this field has involved the use of titanium tetrachloride to promote the reaction of ketene silyl acetals with non-activated imines as an efficient route to P-lactams. This reaction has been applied to the asymmetric synthesis of P-lactams via a chiral imine-titanium tetrachloride template. We have also found that both ketene silyl acetals and vinylketene silyl acetals oxidativelly dimerize or cross-couple, in the presence of titanium tetrachloride to conveniently yield various diesters . Our present study concerns reactions of vinylketene silyl acetals with non-activated imines and vinylimines promoted by titanium and zirconium tetrachlorides. 

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]. 

As already indicated, carbonyl compounds such as ketones, aldehydes, enones, and quinones possess the property to act as effective electron acceptors in the excited state for generating radical anions in the presence of electron-donating partners such as alkenes, aromatics, ruthenium complexes, amines, and alcohols. We will not consider the reactivity of enones and quinones, but we will focus our attention on the behavior of the radical anions formed from ketones and aldehydes. Four different processes can occur from these radical anions including coupling of two radical anions and/or coupling of the radical anion with the radical cation formed from the donor, abstraction of hydrogen from the reaction media to produce alcohols, cyclization, in the case of ce-unsaturated radical anions, and fragmentation when a C -X bond (X=0, C) is present (Scheme 18). 

The synthesis of amines with sulfonic acid groups, 4,4 -bis(4-aminophenoxy)benzophenone-3,3 -disulf-onic acid and 4,4 -bis(4-aminophenylthio)benzoph-enone-3,3 -disulfonic acid, starts from 4,4 -dichlorobenzophenone by sulfonation with sulfuric acid. In the second step, 4-aminophenoI is coupled in the presence of anhydrous potassium carbonate [100]. 

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