Nitrostyrenes addition reactions

Although the enamine (30) underwent addition reaction with ethyl azido-dicarboxylate, it failed to add another mole of jS-nitrostyrene. In a similar manner the morpholine enamine of 2-methylcyclohexanone also failed to react with this olefin, i.e., jS-nitrostyrene, which is undoubtedly due to the 1,3-diaxial interaction between the methyl group and the incoming electrophile in the transition state. 

In the Michael addition reaction of (S )-phenylethylamine and L-alanine isopropyl ester to [Pg.444]

The nitroaldol may be dehydrated to a nitroalkene in the case of nitroaldols arising from aromatic aldehydes this dehydration reaction occurs spontaneously as is illustrated in the preparation of co-nitrostyrene (Expt 6.136). The nitroalkenes are important dienophiles in the Diels-Alder reaction (Section 7.6, p. 1117). An example of the Michael addition reaction is illustrated in the syn-... 

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>. 

Good asymmetric induction is observed in addition reactions when an optically active amine is used as the chiral catalyst. For example, the addition of thiols to /J-nitrostyrene carried out in the presence of various cinchona alkaloids gives chiral sulfides 7. ... 

Soon afterward, various types of carbon [40-44], oxygen [45], and phosphorous [46] Michael donors were successfully employed in the thiourea-catalyzed addition to nitroalkenes. In the presence of the bifunctional epi-9-amino-9-deoxy cinchonine-based thiourea catalyst 79a, the 5-aryl-l,3-dioxolan-4-ones 138 bearing an acidic a-proton derived from mandelic acid derivatives and hexafluoroacetone were identified by Dixon and coworkers as effective pronucleophiles in diastereo- and enantioselective Michael addition reactions to nitrostyrenes 124 [40]. While the diastereoselectivity obtained exceeded 98%, the enantiomeric excess recorded... 

Excellent enantioselectivities for all of these dendrimers were observed in the Michael addition reactions of isovaleraldehyde with nitrostyrene. For example, in the presence of 10mol% of the first-generation catalyst, the addition product 2-isopropyl-4-nitro-3-phenyl-butyraldehyde was isolated in 86% yield with 99% ee and moderate diastereoselectivity (diastereomeric ratio (dr) 80 20). Higher diaste-reoselectivities were observed when the meta-substituted dendrimer catalysts were used, but the yields and enantioselectivities were relatively low. In addition, the second-generation dendrimer catalyst could be easily recovered via precipitahon with methanol and reused at least five times, with only a slight loss of catalytic activity. 

Jorgensen and co-workers reported the enantioselective a-sulfenylation of aldehydes catalyzed by 6b (Equation 10.16) [34]. Hayashi et al. reported the 1,4-addition reaction of acetaldehyde with nitrostyrene in the presence of 6a (Scheme 10.17) [35]. The introduction of a siloxy group into proline increased its catalytic activity, thus allowing for a decrease in catalyst load and reaction time without compromising the... 

To a suspension of 2.0 g LAH in 200 mL cool anhydrous Et20 under an inert atmosphere, there was added a THF solution of 2.0 g 2,5-dimethoxy-4-fluoro-beta-nitrostyrene. The reaction mixture was stirred at room temperature for 2 h and then heated briefly at reflux. After cooling, the excess hydride was destroyed by the cautious addition of H20, and when the reaction was finally quiet, there was added 2 mL of 15% NaOH, followed by another 6 mL of H20. The basic insolubles were removed by filtration, and washed with THF. The combined filtrate and washes were stripped of solvent, yielding a residual oil that was taken up in 10 mL of IPA, neutralized with concentrated HCI, and the generated solids diluted with anhydrous Et20. The white crystalline 2,5-dimethoxy-4-fluorophenethylamine hydrochloride (2C-F) was recrystallized from IPA to give an air-dried product of 0.5 g with a mp of 182-185 C. 

Importantly, prolinamide catalysts (Figure 6.3) work well in Michael addition reactions using nitro-olefins as acceptors. iV-Tritylprolinamide 33 and aminonaphthyridine-derived ProNap 34 served as organocatalysts in asymmetric Michael additions of aldehydes and cyclohexanone to nitro-alkenes. Proline-functionalised C3-symmetric 1,3,5-triallq lbenzene 35 was screened in the reaction of cyclohexanone to nitrostyrene to afford the Michael adducts in good yields and diastereoselectivity but low enantioselectivity. 

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... 

Phosphine-AgOTf complexes are known to promote Michael addition reactions. Kobayashi and Shirakawa have achieved asymmetric Michael addition of P-ketoester to nitroalkenes catalyzed by (R)-Tol-BINAP-AgOTf in water [68]. When cyclopentanone-2-carboxylic acid tert-butyl ester (50) and trans- -nitrostyrene (51) were used as substrates, the Michael adduct (52) was obtained in 71% yield with 77 23 diastereomeric ratio. The major diastereomer showed 78% ee (Scheme 18.19). 

Polymer-bound z-nitrostyrenes on the basis of polystyrene/divinylbenzene and of polyfoxyethylene) represent polymer products usefril for addition reactions with the thiol groups of cysteine peptides or any other thiols in aqueous media. Thus, cysteine peptides can be removed selectively by revm ible addition from peptides mixtures. 

Bridging the gap between organocatalysis and biocatalysis has been attained with the promiscuous enzyme 4-oxalocrotonate tautomerase (4-OT) that has been shown to catalyse the Michael-type addition of acetaldehyde to nitrostyrene. The reaction proceeds in water, affords the (5)-configured product in 89% ee, and is believed to proceed via enamine formation that employs the amino-terminal proline of the enzyme. 2 0... 

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