Michael/Aldol cascade strategy

Overview of Michael/Aldol Cascade Strategy for the Synthesis of Cardenolides... 

The most impressive result of the catalytic Michael-aldol cascade is the kinetic resolution of the racemic cyclopentenone 458 shown in Sch. 64. The reaction is performed with 10 mol % (S)-ALB to give the tandem Michael-aldol adduct 459 in 97 % ee and 75 % yield based on malonate 390f. Asymmetric induction in 459 was measured after dehydration of the hydroxyl group, as was done for 451. Clearly, this demonstrates the viability of this new asymmetric strategy for the synthesis of a variety of fully functionalized prostaglandins. 

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 addition to conventional Diels-Alder reactions, consecutive [4-1-2] reactions have been subjected to extensive investigation through the iminium-enamine catalytic sequence. Wang, Rios, and others simultaneously described enantioselective cascade sulfa-, oxa-, and aza-Michael/aldol/dehydration reactions promoted by chiral secondary amines. An initial strategy for a one-pot synthesis of chiral thiochromenes with good to high enantioselectivities was reported (Schemes 1.46 and 1.47) [71]. 

In 2007, Nicolaou et al. [24] reported the total synthesis and structure elucidation of biyouyanagin A (61), isolated from the leaves of Hypericum Chinese var. salicifolium, a species used in Japan as a folk medicine for the treatment of female disorders [25]. This synthesis involved an organocatalytic Michael addition catalyzed by the praline-derivative catalyst 59 as a key step followed by a cascade intramolecular aldol condensation to achieve the key intermediate enone 60 (68% yield, 86% de), which was subsequently converted to complete the total synthesis of biyouyanagin A (61) by a [2+2] photocycloaddition strategy (Scheme 17.8). The same organocatalytic Michael addition strategy was utilized by the Baran group in... 

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