Michael reaction aldehyde substrates

J0rgensen [111] and Vicario [112] independently described the conjugate addition of both triazole and tetrazole based nucleophiles to a,P-unsaturated aldehyde substrates as an alternative method for C-N bond formation. These reactions were catalysed by the diarylprolinol and imidazolidinone scaffolds with equal efficiency showing the complementarity and efficacy of both these catalyst architectures. In addition, Jprgensen has also shown succinimide to be an effective Michael donor (see Sect. 2.3.5 Scheme 49 for further details) [113]. 

DBU (1) catalyses the formation of 2//-l-benzopyran from salicylic aldehydes and aUenic carbonyl compounds [82]. This reaction could be categorized as a tandem reaction composed of Michael and aldol-type reactions. Wide substrate tolerance on the aldehyde unit is observed. The introduction of a large phenyl group on and use of aUenyl ester diminishes the yield of benzopyrans (Table 3.6). 

Bis(phenylsulfonyl)methane has also been employed as an acidic carbon pronucleophile related to malonates and 1,3-diketones with success in the Michael reaction with ot,p-unsaturated aldehydes using 31c as catalyst (Scheme 3.6). The reaction showed a remarkable substrate scope when alkyl-substituted enals were employed but failed when cinnamaldehyde was tested as Michael acceptor. Alternatively, a more acidic cyclic gem-bissulfone has been used as Michael donor, keeping the high yields and enantioselectivities observed for the reaction and also allowing to expand the scope of the reaction to several aromatic enals.In all cases, the chemistry of the sulfonyl group was employed to generate a methyl group after metal-mediated desulfuration or, alternatively. 

The ability of A -heterocyclic carbenes to activate a,p-unsaturated carbonyl compounds via the formation of the corresponding Breslow intermediate, which plays the role of a homoenolate nucleophile, has also been applied to a cascade process involving a formal intramolecular Michael reaction/oxidation/ lactonization, leading to the formation of complex tricyclic carbon frameworks starting from a bifunctional substrate containing an enone and an a,p-unsa-turated aldehyde side chain linked to each other via a benzene tether (Scheme 7.82). The reaction involved a complex multistep mechanism which started with the activation of the enal by the catalyst, forming the Breslow intermediate, which subsequently underwent intramolecular Michael reaction and next the generated enol-type intermediate reacted intramolecularly with the... 

Chiral pyrrolidines constitute the first class of organocatalysts which have been successfully used to catalyse various domino Michael addition reactions involving other-than-C-nucleophiles. As an example, Wang et al. have reported highly enantio- and diastereoselective domino aza-Michael-Michael reactions of ot,p-unsaturated aldehydes with a trans 4-amino protected cx,p-unsaturated ester catalysed by diphenylprolinol silyl ether combined with NaOAc as a base. As summarised in Scheme 1.75, the corresponding trisubstituted synthetically useful, highly functionalised chiral pyrrolidines were produced in high yields and diastereoselectivities of up to 94% de combined with almost complete enantioselectivity in all cases of substrates. 

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