Nitrostyrenes Michael reactions

Figure 6.26 Multiple hydrogen-bonding tertiary amine-functionalized thioureas screened in the asymmetric Michael reaction between trans-P-nitrostyrene and acetylacetone at 10mol% loading.

Figure 6.38 Cinchonine-derived thioureas (10mol% loading) screened in the Michael reaction of dimethyl malonate to trans- 3-nitrostyrene.

Scheme 6.113 Product range for the 117-catalyzed Michael reaction of dimethyl malonate to various tram-P-nitrostyrenes.

Thiourea catalyst 139 was also screened in the asymmetric Friedel-Crafts reaction between 2-naphthol trans-nitrostyrene (73% yield 0% ee 18 h in toluene at -20 °C and 10 mol%) [277], in the asymmetric aza-Michael reaction of O-benzyl-hydroxylamine to chalcone (72% conv. 19% ee 72 h in toluene at 20 °C and 20mol% catalyst loading) [293], and in the asymmetric Morita-BayUs-HiUman [176, 177] reaction between cyclohexenecarbaldehyde and 2-cyclohexene-l-one (20% yield 31% ee 46 h at rt and 20mol% DABCO and 139) [310]. In aU these transformations, thiourea 139 proved to be not competitive to the organocatalysts probed for these transformations under identical screening conditions and thus was not employed in the optimized protocols. 

Scheme 6.180 Mechanistic proposal for the Michael reaction of cyclohexanone with tram-nitrostyrene catalyzed by 213.

The Michael reactions [149-152] between cyclohexanone and trons-nitroalkenes were also explored by Xiao and co-workers utilizing bifunctional pyrrolidine-thiourea 213 and the pyrrolidine-thioureas 214-217 (Figure 6.61) [344]. The model Michael reaction between cyclohexanone and trons-nitrostyrene identified water as the best solvent and 217 to be the most efficient catalysts concerning the activity and asymmetric induction (90% yield 96% ee dr 98 2 in 12 h at 35 °C) in the presence of benzoic acid (10mol%) as additive. The optimized catalytic system allowed the formation of a broad spectrum of Michael adducts such as 1-6 resulting from... 

A direct organocatalytic Michael reaction of ketones or aldehydes with /3-nitrostyrene has been reported in brine solution, using a bifunctional catalyst system proline-derived diamine (70) and TFA.203 In some cases the conversion, yield, de, and ee all exceeded 95%. Results in water were poor, mainly due to polymerization, which is catalysed by amines. It is proposed that sodium cations stabilize the anionic intermediate formed from (70) and /3-nitrostyrene, thus minimizing polymer formation. While organic co-solvent is not required, an organic-rich phase is proposed to concentrate the Michael reactants and catalysts, thus accelerating the reaction. 

Both a base and an Ir catalyst 6 are necessary to effect diastereoselective sequential Nazarov cyclisation and Michael addition between a pyran-based alkylidene (3-ketoester and a nitrostyrene. The reaction is diastereoselective, leading to substituted cyclopenta[b]pyrans with three stereocentres <06JA5312>. 

Nazarov cyclization is successfully conducted with the phosphoryl triflimide derivative of IB. Michael reaction to combine indole and (3-nitrostyrene occurs on catalysis of 3... 

TBDPS ether (without a-substituents) also mediates Michael reaction of ketones with (3-nitrostyrenes. ... 

Michael reaction. The greatest number of research reports pertaining to methodology development for the asymmetric Michael reaction are based on the addition of ketones to P-nitrostyrene. Among catalysts 2 3 and 4, the first one is the simplest. 

Michael reaction Enantioselective addition of ketones to p-nitrostyrene is performed with the disubstituted triazole 1. Surprisingly, 1 is not a good catalyst for the aldol reaction. 

Figure 9.9 Supposed transition state for thiourea catalysed Michael reaction of nitrostyrene and indole...

Enantioselective Michael reaction of propanal to frans-p-nitrostyrene. 

The first attempts in the field were carried out in the context of the proline-catalyzed Michael reaction of ketones with nitrostyrene, which was initially... 

Figure 2.2 Proposed models for the 2b-catalyzed Michael reaction between ketones and nitrostyrenes.

Figure 2.5 Proposed models for Michael reaction between cyclohexanone and nitrostyrenes catalyzed by pyrrolidine-diamines 14a-c in the presence of a Bronsted acid co-catalyst.

Scheme 2.8 Enantioselective Michael reactions of ketones with nitrostyrenes catalyzed by several primary amines.

Remarkably, the reaction also tolerated the use of differently substituted a-alkyl-p-ketoesters as Michael donors, leading to the formation of compounds containing two contiguous stereogenic centers, one of them a quaternary one, in good diastereo- and enantioselectivities (Scheme 4.6). Masked cyclic 1,3-diketones such as 2-hydroxy-1,4-naphthoquinols have also been successfully applied in this context also showing the extraordinary performance of catalyst 68a in terms of both yields and enantioselectivities. There is also one example of a vinylogous Michael reaction between a,a-disubstituted dicyanoacrylates and nitroalkenes for which Takemoto s catalyst has also been identified as the most efficient promoter of the reaction. Moreover a solid-supported version of this catalyst has also been developed by Takemoto himself and tested in the reaction of diethylmalonate with nitrostyrene with success. ... 

Figure 4.4 The two proposed models explaining the 68a-catalyzed Michael reaction of malonates with nitrostyrenes.

Scheme 4.7 Influence of cinchona catalysts structure on the yield and enantioselec-tivity of the Michael reaction of dimethyl malonate with nitrostyrene.

Acetylacetone has also been the subject of several studies when used as 1,3-dicarbonyl compound suitable to engage in a Michael reaction with nitroalkenes under H-bonding catalysis. In this context, Takemoto s catalyst 68a and valine-derived thiourea 74 have been tested in the reaction with acetylacetone with nitrostyrene furnishing good results, although no extensive study was carried out in order to evaluate the substrate scope with regard to the substitution at the nitroalkene. On the other hand, several functionalized thioureas have been expressly surveyed in this reaction, providing a detailed study... 

In a different work, A-sulfonylamido 9-epi quinine catalyst 85 was also successfully employed in the Michael reaction of (3-ketoesters to nitrostyrenes, also suggesting the same type of activation profile (Scheme 4.25). In this case. 

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