Iminium activation nucleophiles

The catalytic cycle operating for a generic Michael-type reaction of a nucleophile (Nu-H) to an a, 3-unsaturated aldehyde or ketone proceeding via iminium activation has been indicated in Scheme 3.1. As it can be seen in this proposed mechanism, all the steps involving iminium formation and hydrolysis are supposed to be in dynamic equilibrium, therefore concluding that the conjugate... 

Oxindoles are a particular class of cyclic amides which are acidic enough to play the role of pro-nucleophiles in conjugate additions under iminium activation. In particular, the reaction between 3-alkyl substituted oxindoles and ot,p-unsaturated aldehydes leading to the formation of a quaternary stereocenter at the heterocyclic unit has been studied by several authors (Scheme 3.12). The use of 0-trialkylsilyldiarylprolinols like 31a as catalysts led... 

Alternatively, the iminium-activation strategy has also been apphed to the Mukaiyama-Michael reaction, which involves the use of silyl enol ethers as nucleophiles. In this context, imidazolidinone 50a was identified as an excellent chiral catalyst for the enantioselective conjugate addition of silyloxyfuran to a,p-unsaturated aldehydes, providing a direct and efficient route to the y-butenolide architecture (Scheme 3.15). This is a clear example of the chemical complementarity between organocatalysis and transition-metal catalysis, with the latter usually furnishing the 1,2-addition product (Mukaiyama aldol) while the former proceeds via 1,4-addition when ambident electrophiles such as a,p-unsaturated aldehydes are employed. This reaction needed the incorporation of 2,4-dinitrobenzoic acid (DNBA) as a Bronsted acid co-catalyst assisting the formation of the intermediate iminium ion, and also two equivalents of water had to be included as additive for the reaction to proceed to completion, which... 

The phospha-Michael reaction has been the last hetero-Michael reaction to be developed under iminium activation. In addition to the selectivity issues that have to be addressed, the identification of a suitable phosphorous nucleophile has been the most difficult task to overcome when developing the reaction because of the high tendency of phosphines toward oxidation in the presence of air. The first example was developed independently by Melchiorre and... 

Heteroatom nucleophiles were described less often. Ye and coworkers published a phospha-Michael addition catalysed by prolinol silyl ether catalyst. Another method for constructing a new C-N bond is the aza-Michael addition, that is the addition of nitrogen-based nucleophiles to a,(3-unsaturated aldehydes. Several groups published these type of reactions using diatylprolinol silyl ether as catalyst. " Fustero and coworkers used this reaction as a key step in the synthesis of biologically active chiral heterocycles. Recently, the authors showed the synthesis of quinolizidine alkaloids, such as (-l-)-myrtine, (-)-lupine and (-l-)-epiquinamide. Vicario applied 5-mercaptotetrazoles as nucleophiles towards a range of unsaturated aldehydes. The reaction proceeded via the iminium activation. The... 

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