Reactions of Nitroolefins

Polymer-supported organocatalysts are valuable materials for conducting catalytic asymmetric transformations under simple and environmentally begnin conditions [275]. A novel polymer-supported diphenylprolinol trimethylsilyl ether was synthesized by Hansen et oi. [276], and further applied as catalyst to induce a diastereo- and enantioselective three-component domino Michael/Michael/aldol 

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 

The same year, Hayashi et I. [285] reported an asymmetric synthesis of substituted tetrahydropyranols through a sequence of reactions beginning with 

In addition, a four-component domino Michael/nitro-Mannich/lactamization reaction was recently developed by Dixon et al. [286]. It occurred between a 

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The regiochemical control of Pd-catalyzed hydride transfer reaction is much more effective than that of the radical denitration, as shown in Eq. 7.98. The base-catalyzed reaction of nitroolefins with aldehydes followed by denitration provides a new synthetic method of homoallyl alcohols (Eq. 7.99).140 Exomethylene compounds are obtained by denitration of cyclic allylic nitro compounds with Pd(0), HC02H and Et3N (Eq. 7.100).140b... 

Nitroolefins are attractive alternative acceptors to enones. In 1999, Barnes and Ji reported an efficient catalyst system for reaction of nitroolefins with 1,3-dicarbonyl compounds with high enantioselectivity (up to 97% ee Scheme 19) [22], Using this method, a highly functionalized nitro compound 38, an important intermediate in the synthesis of an endothelin-A antagonist, was prepared on a large scale in 88 % ee. In this case, the formation of a chiral Mg enolate as a reactive intermediate was proposed. 

Scheme 19. Catalytic reaction of nitroolefins with 1,3-dicarbonyl compounds.

Table 6.7 Cinchona alkaloid-catalyzed Michael reactions of nitroolefins.

A similar reaction of nitroolefins with kctcnc silyl acetals provides y-keto esters but in this case only TiCE is an effective catalyst. Yields arc low unless titanium(IV) iso-propoxidc is added to suppress hydrolysis of the ketene silyl acetals. 

Table 9.13 Thiourea catalysed Michael reaction of nitroolefins with indole...

Seebach studied the conjugate addition reaction of nitroolefin 10 with butyllith-ium in the presence of the multidentate ligand 11 (accessible from tartaric acid), which yielded the adduct 12 in up to 58% ee (Scheme 4) [18]. 

Other examples of Michael additions are the reaction of nitroolefins with acetone on L-proline-modified Mg-Al mixed oxides (51) or with diethyl malonate on metalorganic MCM-41 (52), or the addition of nitromethane to unsaturated carbonyl compounds on KF-modified alumina (53). Furthermore, solid catalysts such as montmorillonite clays and hydroxyapatite have recently been employed for the construction of S—C bonds by /lia-Michael addition of thiols to unsaturated ketones and other carbonyl compounds (54,55). Similarly, aza-Michael additions of amines to alkenes activated by -CN, -COOR, or -COR groups, lead to C—N bond containing products on Amberlyst-15 or polyaniline supported Cul (56,57). 

Polysubstituted 3,4-dihydro-3-nitro-2ff-chromans are obtained from the enantioselective Michael—Michael cascade reaction of chalcone enolates and nitromethane catalyzed by bifunctional thiourea 19 (Scheme 31) (13JOC6488) and tandem Friedel—Crafts alkylation—Michael addition reaction of nitroolefin enoates and 1-methylindole promoted by Zn(OTf)2 (13S601).A squaramide-tertiary amine catalyst promotes the asymmetric sulfa-Michael—Michael cascade reaction of thiosalicylates with nitroalkene enoates which leads to polysubstituted chromans in high yields with excellent stereoselectivities (13OL1190). 

Scheme 8.48 Cul-catalyzed synthesis of polysubstituted imidazole derivatives via intermolecular [3+2] cycloaddition reaction of nitroolefins and amidines.

The synthetic utility of the bifunctional catalysts in various organic transformations with chiral cyclohexane-diamine derived thioureas was estabhshed through the works of Jacobsen, Takemoto, Johnston, Li, Wang, and Tsogoeva. In the last decade, asymmetric conjugate-type reactions have become popular with cinchona alkaloid derived thioureas. The next section presents non-traditional asymmetric reactions of nitroolefins, enones, imines, and cycloadditions to highhght the role of chiral Br0nsted base derived thiourea catalysts. 

Although heterocycUc ortho-quinodimethanes (oQDMS) have been studied extensively to design Diels-Alder reactions for the synthesis of complex indole alkaloids for more than 30 years, asymmetric catalysis of the Diels-Alder reaction of nitroolefins 32 or methylene-indolinones 39 with in situ generated heterocyclic... 

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