Nitrostyrenes domino Michael reactions

In the domino Michael/alkylation reaction applied to the synthesis of 3-(2H)-furanones, the ethyl 4-bromoacetoacetate 203 and nitrostyrene 204 were first trialed with a range of catalysts. In this instance, the so-called modified Feist Binary reaction was completed with an I-threonine bifunctional tertiary amine/thiourea catalyst 205 to produce the furanone 206 in excellent yield and high enantioselec-tivity (Scheme 7.42) [107]. In another report, the furan ring as part of other bicyclic or tricyclic systems was also prepared through an enantioselective Michael addi-tion/nucleophilic substitution reaction (Scheme 7.43) [108]. When diketones and ( )-P,P-bromonitrostyrenes 207 were stirred, again with a bifunctional thiourea... 

Finally, Sankararaman et al. have reported the synthesis of chiral nitro-chromenes on the basis of an asymmetric domino Michael-Henry reaction followed by dehydration, involving nitrostyrene and orlho-hydio-xybenzaldehyde. This reaction was catalysed by a novel C2-symmetric bis-(pyrrolidine-triazole)-based organocatalyst and provided only moderate yields (22-40%) and poor enantioselectivities (7-24% ee). 

In 2013, Li et al. reported a novel synthesis of chiral six-memhered spir-ocyclic oxindoles bearing five consecutive stereocentres on the basis of an enantioselective three-component domino Michael-Michael-aldol reaction catalysed hy a combination of a chiral diphenylprolinol silyl ether and a chiral bifunctional quinine thiourea. " As shown in Scheme 2.26, the reaction between iV-substituted oxindoles, nitrostyrenes, and enals led to the corresponding highly substituted spirocyclic oxindoles in high yields, moderate diastereoselectivities of up to 44% de, and enantioselectivities of up to >99% ee. A large variety of substrates could be used well in this... 

Related Michael-initiated sequential spirocyclizations involving nitrostyrenes as Michael acceptors and functionalized oxindoles as pronucleophiles have been proposed by Lu and coworkers [36]. Alternatively, ( )-p-bromo-p-nitrostyrenes (68) were obtained via a Michael/a-alkylation domino reaction [37]. The reaction was simply catalyzed by the bifunctional Brpnsted Acid-Lewis base catalyst XVII, rendering the final spirocyclopropanes 69 in good yields and excellent stereoselectivities, after epimerization with base (Scheme 10.23). 

A protonated O-TMS-diphenylproUnol 103/BzOH catalytic system was used by Ni et al. in an asymmetric domino Michael/Henry reaction in an aqueous medium. Chiral Michael adducts 107 generated in situ from pentane-1,5-dial (106) and (i-nitrostyrene derivatives spontaneously underwent an intramolecular Henry reaction under the proposed conditions to afford 3-substituted 2-nitro-4-formylcyclohexanols 108 containing four stereocenters in moderate to high yields and with almost complete enantioselectivity (Scheme 22.31) [116]. The catalyst could be recycled at least four times, with only a slight reduction in yields and diastereoselectivity. 

In the same context, these authors reported the synthesis of chiral 2,3,4-trisubstituted thiochromanes by using a cupreine-catalysed domino thia-Michael-Henry reaction, occurring between 2-mercaptobenzaldehydes and nitrostyrenes. As shown in Scheme 1.82, the resulting products were... 

When nitrostyrenes and dimethylmalonate were reacted with a,p-un-saturated aldehydes in the presence of a combination of chiral diphenyl-prolinol triethylsilyl ether and a chiral cinchona alkaloid catalyst through a three-component reaction, Xu et al. showed that they afforded, according to a Michael-Michael-aldol domino reaction, the corresponding chiral functionalised cyclohexanes in moderate to good yields, good to excellent enantioselectivities of up to >99% ee, albeit moderate diastereoselectivities... 

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