Conjugate addition, organocatalysis iminium catalysis

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... 

Since its rediscovery by MacMillan in 2000, iminium activation catalysis has become a key catalytic concept in organocatalysis. After initial work centered on cycloadditions, Michael additions became the main area of interest and it is now estabhshed as a general strategy for the asymmetric conjugate addition of nucleophiles to a,P-unsaturated compounds. 

Iminium-based organocatalysis is somewhat less explored than enamine-based organocatalysis and has been mostly used in the activation of a,/S-conjugated aldehydes and ketones. Therefore, this type of catalysis has unsurprisingly been the subject of a limited number of studies under the umbrella of the metal-organic cooperative catalysis concept. In 2011, the Cdrdova group [55] reported the first enantioselective and chemoselective /3-silyl addition to a./S-unsaturated aldehydes using copper salts and chiral pyrrolidine derivatives as catalysts. As proposed, the chiral secondary amine forms an iminium salt with... 

---