Michael/aldol cascade cyclohexanes

On the other hand, a triple Michael/Michael/Aldol cascade sequence has been developed for the synthesis of highly substituted cyclohexanes starting from dimethylmalonate, an a,p-unsaturated aldehyde and a nitroalkene in which H-bonding catalysis and iminium activation were jointly employed for the simultaneous activation of the two Michael acceptors involved in the... 

Following a similar reaction design, a cascade Michael/aldol reaction has been studied using other different 1,3-dicarbonyl compounds for the building up of highly functionalized cyclohexanes containing multiple stereogenic... 

In 2009, Dixon and co-workers [73] developed a nice cascade reaction for the synthesis of cyclohexanes using a similar strategy. Malonates (119), nitroalkenes 28 and a, 3-unsaturated enals 15 reacts in a Michael-Michael-aldol reaction sequence forming the cyclohexanes 122 in good yields and stereoselectivities. The reaction... 

In 2(X)9, Xu et al. group reported a cascade Michael/Michael/aldol reaction by the combination of secondary amines and bifimctional quinine-derived thioureas, giving rise to polysubstituted cyclohexanes with multiple chiral centers and substituted patterns from readily available malonates, nitroalkenes, and enals with satisfactory yield and high enantioselectivities (Schane 9.34) [31]. Initially, a bifunctional base/... 

A similar cascade reaction was reported by Melchiorre and co-workers [69] in 2008. Initially, this triple cascade reaction between an enolizable aldehyde, 2-cyanoacrylate, and enal consists of the aldehyde addition to a 2-cyanoacrylate derivative (108), promoted by a diphenylprolinol derivative (VII). Next, the resulting adduct reacts with enal via a Michael addition promoted by the same catalyst. Finally, an intramolecular aldol reaction takes place between the formed enamine and the aldehyde, leading to the cyclohexane 109. It should be noticed that the use of an acid as a co-catalyst is cmcial to obtain high levels of stereoselectivity. 

More recently, Enders et al. disclosed a facile access to tetracyclic double annulated indole derivatives 175, which basically relies on the chemistry of the acidic 2-substituted indole and its nitrogen nucleophilicity. Indeed, the employed quadruple cascade is initiated by the asymmetric aza-Michael-type A-alkylation of indole-2-methylene malono-nitrile derivative 174 to o,p-unsaturated aldehydes 95 under iminium activation (Scheme 2.57). The next weU-known enamine-iminium-enamine sequence, which practically is realized with an intramolecular Michael addition followed by a further intermolecular Michael and aldol reactions, gives access to the titled tetracyclic indole scaffold 175 with A-fused 5-membered rings annulated to cyclohexanes in both diastereo- and enantioselectivity [83]. 

---