Imines conjugate addition

Thus, the asymmetric catalysis of cyanoethoxycarbonylation, cyanophosphoryla-tion, epoxidation of electron-deficient olefins, Michael reactions of malonates and (3-keto-esters, Strecker reaction of keto-imines, conjugate addition of cyanide to a, (3-unsaturated pyrrole amides, ring opening of meso aziridines with TMSCN and cyanosilylation of ketones (example shown below) have been successfully carried out using these complexes as asymmetric catalysts. 

Both primary and secondary amines add to a /S-unsaturated aldehydes and ketones to yield /3-amino aldehydes and ketones rather than the alternative imines. Under typical reaction conditions, both modes of addition occur rapidly. But because the reactions are reversible, they generally proceed with thermodynamic control rather than kinetic control (Section 14.3), so the more stable conjugate addition product is often obtained to the complete exclusion of the less stable direct addition product. 

Non-enolizable imines such as 9-fluorene imines react with alkynylcarbene complexes to afford mixtures of mesoionic pyrrolium carbonyltungstates and dihydropyrrole derivatives [68] (Scheme 23). Although both compounds can be considered as [3C+2S] cycloadducts, formation of each of them follows a very different pathway. However, the first intermediate of the reaction is common for both compounds and supposes the conjugated addition of the imine to the alkynylcarbene complex to form a zwitterionic intermediate. A cyclisation... 

Ye and co-workers have shown that NHC 67 can catalyse the aza-Morita-Bay-lis-Hillman reaction of enones 66 and N-tosyl imines 63, presumably via initial NHC conjugate addition to the enone to generate an azolium enolate 68 [18]. A related conjugate addition approach has been exploited by Fu and co-workers, with tautomerisation of the initial enolate 72 derived from NHC conjugate addition to 70 giving 73, with subsequent cyclisation resulting in the umpolung of Michael acceptors (Scheme 12.13) [19]. 

Allenylsilanes undergo intramolecular additions to appropriately positioned aldehydes, imines, conjugated esters and alkenes to afford various alkynylcyclopentane and cyclohexane derivatives (Eqs. 9.66-9.70) [66]. The reactions are promoted by SnCl4 or by thermolysis. The stereochemistry of these cyclization reactions is consistent with a concerted sigmatropic process as illustrated in Scheme 9.17. 

Yamamoto and coworkers described a highly enantioselective asymmetric domino 0-nitroso aldol-conjugate addition seqnence using cyclic enones 221 and aromatic nitroso compounds 222 as depicted in Scheme 36 [346]. A related reaction with imines was also reported by Cdrdova and coworkers (Scheme 37) [228]. 

Scheme 37 Domino imine aldol-conjugate addition...

Asides from the application of imines on conjugate addition reactions, Deng [87, 88] reported the first asymmetric chiral thiourea catalyzed Friedel-Crafts reaction of indoles with iV-tosyl imines (Scheme 35). The reaction was receptive to various aromatic, heteroaromatic, and aliphatic imines in good yield and high enantioselec-tivity (Scheme 36). 

TABLE 9. Asymmetric conjugate addition of organolithium reagents to a,/ -unsaturated esters and imines in the presence of chiral diether hgand 28 or (—)-sparteine (29) ... 

Ornithine decarboxylase is a pyiidoxal dependent enzyme. In its catalytic cycle, it normally converts ornithine (7) to putiisine by decarboxylation. If it starts the process with eflornithine instead, the key imine anion (11) produced by decarboxylation can either alkylate the enzyme directly by displacement of either fluorine atom or it can eject a fluorine atom to produce viny-logue 12 which can alkylate the enzyme by conjugate addition. In either case, 13 results in which the active site of the enzyme is alkylated and unable to continue processing substrate. The net result is a downturn in the synthesis of cellular polyamine production and a decrease in growth rate. Eflornithine is described as being useful in the treatment of benign prostatic hyperplasia, as an antiprotozoal or an andneoplastic substance [3,4]. 

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