Nitro Michael reactions

Figure 1.15 Supramolecular catalysts for organocatalysis (a) Route to catalyst libraries (b) asymmetric nitro-Michael reaction.

Palomo et al. have extended the range of nucleophiles amenable in asymmetric organocatalysed Michael reactions of nitronates and malonates to oc,P-unsaturated aldehydes Inspired by the prolinol motif, they proposed a series of derivatives, among which 21 was the most efficient catalyst for the nitro-Michael reaction of Scheme 1.11 and the Michael reaction of Scheme 1.12. These reactions required the use of benzoic acid as co-catalyst to optimize results. 

Asymmetric nitro-Michael reactions of methyl vinyl ketone (MVK) in the presence of bicyclic guanidine with a benzhydryl group led, disappointedly, to low asymmetric induction (9-12%) [21a] Trials for the reaction of 0 ,p-unsaturated y- or 8-lactones with pyrrolidine in the presence of the conjugate acids of a bicyclic guanidine [50] or the Murphy s guanidine [24a] (R = Me in Scheme 4.7) resulted in the production of racemic compounds. The latter phase transfer catalyst (PTC) catalyses the nitro-Michael addition of chalcone but with limited range (70% yield, 23% ee) [24c]. 

Excellent conversions and selectivities were observed both with respect to the alkene and the primary oxidant [62]. In nitro-Michael reaction it was noted that the Murphy s PTC does not work as a good chiral catalyst for the Michael reaction of chalcone, but the same PTC effectively catalyses the epoxidation of chalcones with sodium hypochlorite (NaOCl) [24c]. Trials for the epoxidation of chalcone in the combination of hydroperoxides and modified guanidines 19 [27b] resulted in less effective asymmetric induction compared to the Murphy s PTC [53] (Scheme 4.21). 

The next series of syntheses is based on conjugate additions. A 2-arylcyclo-hexanone was regio- and stereoselectively added to nitroethylene to access the octahydroindole core present in the alkaloids. This has enabled the total synthesis of (+j-y-lycorane and (+)-crinane (280). Tomioka described a chemoselective conjugate addition - nitro Michael reaction sequence to prepare a- and -lycoranes in their racemic form (281). The addition of an arylcuprate to a D-mannitol-derived... 

Seheme 19.81 Enantioselective nitro-Michael reaction employing thiourea 69. 

Other-than-proline derivatives have been successfully employed to catalyse a great number of asymmetric nitro-Michael reactions. Therefore, excellent... 

Portnoy and coworkers immobilized chiral hydroxyproline derivatives on polystyrene support functionalized with polyether dendrons (Scheme 15.45).These catalysts promoted the aldol addition of acetone to aromatic aldehydes with excellent enantioselec-tivities, significantly superior to those achieved in the same reaction with analogous catalyst lacking the dendritic interface. The same group prepared polymer-supported chiral bifunctional aminocarbamate and aminourea catalysts for nitro-Michael reaction (Scheme 15.46). However, in this case the dendritic catalysts were inferior to their simpler dendron-lacking analogues. 

Tsogoeva et al developed a novel bifunctional thiourea catalyst (12), derived from 1,2-diaminocyclohexane, and applied it to the Strecker synthesis and nitro Michael reactions (Scheme 2.47) [100]. 

Figure 5.6 Proposed transition state for the nitro-Michael reaction catalyzed by H-Pro-Phe-OH.

Complementary hydrogen-bonding interactions have also been used by the group of Clarke [18, 19] for the construction of catalyst libraries based on the self-assembly of chiral prohne-derived pre-catalyst 8 [designated (S)-ProNap] with a series of achiral substrates (Figure 9.3). These studies were aimed at modulating the stereoselectivity of the asymmetric nitro-Michael reaction of ketones and nitrostyrenes simply by modifying the achiral co-catalyst. Since catalyst formation relies on self-assembly, this provides easy access to a catalyst Hbrary with different... 

Figure 9.3 (a) Asymmetric nitro-Michael reaction of ketones and nitrostyrenes catalyzed by self-assembled complexes (b) (c) best performing pre-catalytic unit 8 and achiral additive 9. 

Scheme 22.9 IL-mediated asymmetric nitro-Michael reactions in the presence of pyrrolidine-phosphite 25.

Figure 9.3 (a) Asymmetric nitro-Michael reaction of ketones and nitrostyrenes catalyzed by... 

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