Nitro Michael reaction catalysts

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). 

Ley and coworkers also used tetrazole 5a to catalyse the asymmetric Michael addition of a ketone to an aromatic nitro-olefin in a 1 1 mixture of ethanol and isopropanol. The products obtained had moderate to good diastereoselectivities (up to >19 1 dr) and moderate enantioselectivities (up to 73% ee). Further, a homoproline tetrazole derivative (5b) was prepared and used for asymmetric Michael reaction. Catalysts 5a and 5b gave similar diastereoselectivities however, the catalyst 5b produced products with higher enantioselectivities in the Michael addition of ketones to aromatic nitro-olefins (Scheme 9.34). Ley and coworkers explained that the side chain of the homotetrazole was responsible for the increased enantioselectivity. 

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]. 

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... 

Heterobimetallic asymmetric complexes contain both Bronsted basic and Lewis acidic functionalities. These complexes have been developed by Shibasaki and coworkers and have proved to be highly efficient catalysts for many types of asymmetric reactions, including catalytic asymmetric nitro-aldol reaction (see Section 3.3) and Michael reaction. They have reported that the multifunctional catalyst (f )-LPB [LaK3tris(f )-binaphthoxide] controls the Michael addition of nitromethane to chalcones with >95% ee (Eq. 4.140).205... 

Bifunctional thiourea-catalysed enantioselective Michael reaction has been achieved. The thiourea moiety and an amino group of the catalyst activated a nitroolefin and a 1,3-dicarbonyl compound, respectively afford the Michael adduct with high enantioselectivity.177,178 Thioureas work as one of the most effective and general enantioselective nitro-Mannich reaction and carbonyl cyanation catalyst.179,180... 

Terada expanded the phospha-Michael reaction to include diphenyl-phosphites [128]. A novel binaphthol-derived guanidine catalyst promoted the addition in high yields and enantioselectivities (Scheme 73). Functionalizing the external nitrogen with a diphenylmethine moeity enhanced selectivities for a large scope of nitro-olefm derivatives. 

The modification of thiourea catalyst 93 through incorporation of the (S,S)-diaminocyclohexane backbone as an additional chirality element and a Schiff base imidazoyl-moiety led to the bifunctional catalyst 94 that, in contrast to 93 in the Strecker reaction (Scheme 6.99), exhibited enantioinduction (83-87% ee) in the nitro-Michael addition of acetone to trons-P-nitrostyrenes. The desired adducts were isolated in moderate yields (46-62%) as depicted in Scheme 6.100) [259]. 

Cobb, A.J.A., Shaw, D.M., Longbottom, D.A., Gold, J.B. and Ley, S.V. (2005) Organocatalysis with proline derivatives improved catalysts for the asymmetric Mannich, nitro-Michael and aldol reactions. Org. Biomol. Chem., 3, 84. 

Ni(II)(OAc)2bpy and Co(II)(OAc)2bpy catalyze the Michael addition of nitro-methane, malononitrile, and aniline to a,j8-unsaturated ketones, methyl acrylate, and acrylonitrile in DMF under neutral conditions [116]. FeCls 6H2O is a highly efficient catalyst of Michael reaction of 1,3-dicarbonyl compounds with a,/3-unsaturated ketones under mild and neutral conditions (Sch. 24) [117]. There is literature precedent for this reaction with dual catalysis Ni(II) immobilized on a clay support and FeCl3 to activate the enone [118]. The mechanism proposed for the single-center catalysis involves coordination of the enone to a diketonato complex [119]. The chemo-... 

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