Michael-aldol-dehydration

Scheme 7.3 Enantioselective Michael/aldol/dehydration cascade reaction for the synthesis of functionalized cyclohexenes.

Scheme 7.16 Synthesis of cyclohexenones by cascade Michael/aldol/dehydration sequence.

Scheme 7.17 One-pot procedure for the synthesis of cyclohexenones by Michael/ aldol/dehydration/decarboxylation sequence.

Scheme 7.20 Cascade Michael/aldol/dehydration reaction for the formation of cyclopentenes.

Using this approach, benzothiopyrans have been prepared by means of a sulfa-Michael/aldol/dehydration cascade and access to dihydroquinolines has been achieved by using an aza-Michael/aldol/dehydration approach (Scheme 7.52). In general, all these reactions proceeded with excellent yields and... 

Scheme 7.51 Oxa-Michael/aldol/dehydration cascade for the synthesis of benzopyranes.

Most recently, a new bifunctional phosphine catalyst, (2 -hydroxybiphenyl-2-yl)-diphenylphosphane 225, has been developed for the selective aza-MBH reaction and aza-MBH domino reaction of iV-sulfonated imines with acrolein under mild conditions in moderate to excellent yields (Scheme 2.111). The possible catalytic cycle of the domino reaction and aza-MBH reaction has been proposed. The aza-MBH/Michael/aldol/dehydrate domino reaction also provides an efficient method to synthesize tetrahydropyridine... 

Scheme 10.23 Three-component domino Michael/Michael/aldol/dehydration reaction.

Wang et al. [49] obtained enantioenriched thiochromenes through a cascade sulfa-Michael-aldol-dehydration reaction between 2-mercaptobenzaldehydes and a,p-unsaturated aldehydes, catalyzed by 17a (Scheme 14.17a). Cordova and coworkers [50] obtained comparable results despite some minor changes of the reaction conditions. An analogous process with cyclic enones afforded tetrahydrothioxanthe-nones in only moderate enantioselectivities (Scheme 14.17b). In this case, chiral pyrrolidines 18 and 19 gave the best results in terms of enantioselectivities [51]. 

SCHEME 16.29. Enantioselective aza-Michael/aldolization/dehydration cascade for the access to 1,2-dihydroquinolines. 

SCHEME 16.41. Oxa-Michael/aldol/dehydration organocascade for the enantioselective synthesis of chromenes. 

Scheme 2.5 Domino Michael-aldol-dehydration reaction catalysed by a combination of a chiral diamine and a chiral dicarboxylic acid.

Zhao and coworkers devised enantioselective syntheses of chiral cyclohexenones using primary-secondary diamine-catalyzed cascade reactions (Scheme 3.17). Diamine 13b promoted a cascade Michael-aldol-dehydration reaction between ketoester 77 and enones 78, affording highly functionalized chiral cyclohexenones 79 in good yields and with high enantioselectivities, although the diastereoselectiv-ity was poor [52]. The same group also applied a similar approach for an enantioselective synthesis of fluorinated cyclohexenones via Robinson annulation reaction [53]. 

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 a continuation of enantioseleclive cascade sulfa-, oxa-, and aza-Michael/aldol/ dehydration cascade reactions, Wang et al. envisioned that the employment of a nucleophilic carbon atom for the initial Michael addition could enable the generation of two new C—C bonds in sequential [3+2] reactions. 

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