Nitro-Michael addition

Scheme 6.100 Products of the asymmetric nitro-Michael addition of acetone to frans-P-nitrostyrenes catalyzed by thiourea 94.

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]. 

L-Prolinamides (71) with a pendant alcohol act as recoverable bifunctional catalysts of direct nitro-Michael addition of ketones to -nitrostyrenes, giving syn-de s up to 94% and ees up to 80%.204 The pyrrolidine provides enamine catalysis, and the side-chain donors can hydrogen-bond the nitro oxygens. 

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]. 

In a model synthesis <81CC524>, a nitro-Michael addition of the readily available nitroalkyl pyrrole 36 to mesityl oxide was used to introduce a geminally dimethylated structural element into an AD component rac-39 for the desired chlorin. Reduction of the nitro function in rac-37 leads to the desired AD dimer rac-38 which is combined in the presence hydrobromic acid with the well known a-bromo-a -bromomethyl dipyrromethene 40 after acid induced ester clevage and decarboxylation to yield the tetrapyrrolic biline rac-41. In the final step the linear tetrapyrrole rac-41 undergoes oxidation and cyclization in the presence of copper(II) acetate to give the copper chlorin. The cyclization occurs via the enamine tautomer of rac-41 by nucleophilic attack of the enamine structure on the bromo imine part of the linear tetrapyrrole. 

Various i-prolinamides, derived from chiral p-amino alcohols, are active hifunctional catalysts for nitro-Michael additions of ketones to p-nitrostyr-enes. In particular, catalyst 25e exhibits the highest catalytic performance working in polar aprotic solvents. 

Scheme 13.19 Proposed mechanism of nitro-Michael addition reactions catalysed by N-terminal primary amino dipeptides.

In another one-pot reaction, chiral isoxazoline-fused benzazepines 31 were formed from the reaction of P-nitrostyrene derivatives 30 and 1,3-dicarbonyl species such as dimethyl malonate. The first step is a nitro-Michael addition reaction between the nitro olefin and dimethyl malonate catalyzed by a chiral thiourea organocatalyst, followed by addition of DMAP and Boc anhydride with heating to promote nitrile... 

Intermolecular Domino Nitro-Michael Additions of C-Nucleophiles... 

A number of highly efficient asymmetric domino nitro-Michael additions of C-nucleophiles catalysed by organocatalysts were described in 2008. One of the most employed organocatalysts for these types of reactions is diphenylprolinol silyl ether. This catalyst was used by Hong et al. to develop a highly diastereo-and enantioselective domino reaction occurring between 7-oxohept-2-enoate and nitroalkenes (Scheme 1.61). ° The reaction afforded highly functionalised... 

Figure 9.4 (a) Asymmetric nitro-Michael addition of ketones to nitrostyrenes catalyzed by catalytic complexes obtained through self-assembly (b) (c) examples of catalytic and... 

It has been shown that the combination of water and microwave irradiation promotes the catalyst free nitro Michael addition of pyrroles and indoles with good yields (99%) (Rosa and Soriente, 2010). 

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