Domino Michael aza -Henry Reactions

Also in 2008, Xu et al. [158] developed a novel domino oxa-Michael/Henry reaction of 2-hydroxybenzaldehydes with nitroalkenes, providing the corresponding 

The process was efRciently catalyzed by a chiral pyrrolidine in the presence of salicylic acid. It must be noted that Zhao et al. [159] had previously developed, in 2007, a similar reaction for the synthesis of chiral thiochromanes through domino oxa-Michael/Henry reaction of 2-mercaptobenzaldehydes with ititrostyrenes catalyzed by a simple chiral cupreine. The corresponding chiral 2-aryl-3-ititrothiochroman- 

4- ols were achieved in good yields (84-97%) with enantioselectivities of up to 86% ee and diastereoselectivities of up to 56% de. In addition, several groups have developed domino Michael/aza-Henry reactions catalyzed by chiral thioureas. 

The scope of this methodology was applied to the synthesis of chiral functionalized 

An early example of an asymmetric domino Michael/Knoevenagel reaction was reported by Jorgensen et al. [167] in 2006, providing the synthesis of chiral cyclohexenones from the reaction of tert-butyl 3-oxobutyrate and a, 3-unsaturated aldehydes catalyzed by chiral diphenylprolinol silyl ether derivative. Soon after, the 

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Scheme 10.29 Three-component domino Michael/aza-Henry reaction.

Organocatalytic Asymmetric Synthesis of Five-Membered Cycles 11109 37.2.2.1.5 Domino Michael-(aza]-Henry Reactions... 

It must be noted that Xu et al [283] had previously reported the enantioselective synthesis of fully substituted chiral N-tosylpiperidines arisen from the domino Michael/aza-Henry/hemiaminalization reaction of aldehydes, tosylimines, and... 

Another enantioselective approach to tetrahydroquinolines (compounds 87) was developed by Xu and is based on a Michael-aza-Henry domino process, which is shown in Scheme 3.26 [68]. The reactions were catalyzed by a bifunctional thiourea 86 and proceeded in excellent yields and enantioselectivities, with diastereomeric excesses of up to 90%. 

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