Nitroethylene Michael addition

Papai et al. selected as model reaction the addition of 2,4-pentanedione (acetylacetone) to trans-(R)-mtrostyvQnQ, catalyzed by the bifunctional thiourea catalyst shown in Scheme 6 [46]. The analogous Michael-addition involving dimethyl malonate and nitroethylene as substrates, and a simplified catalyst was calculated at the same level of theory by Liu et al. [47]. Himo et al. performed a density functional study on the related cinchona-thiouTQa catalyzed Henry-reaction between nitromethane and benzaldehyde [48]. 

In contrast to the reactivity of the nitroethylenes, acrylonitrile generally reacts with indoles to form the l-(2-cyanoethyl) derivatives (B-70MI30500,79MI30501), whereas Michael addition at the 3-position requires the catalytic effect of copper(II) salts. The addition-elimination reaction of pyrroles and indoles with l,l-dicyano-2-ethoxyethylene proceeds in low yield (<30%) to give the dicyanovinyl derivatives, which can be converted by standard procedures into the formyl compounds (81H(16)1499). Tetracyanoethylene forms charge transfer complexes with indoles, which collapse to the Michael adduct anions and subsequently eliminate a cyanide ion with the formation of the tricyanovinylindole (B-70MI30500). 

Asymmetric Michael addition to to-nitrostyrenes,2 The enamine (2) formed from cyclohexanone and this prolinol derivative reacts with 2-aryl-1-nitroethylenes (3) to form, after acid hydrolysis of the primary adduct, essentially only one (4) of the four possible y-nitro ketones. 

Tn and coworkers reported on both kinetically and thermodynamically controlled Michael addition of the lithinm enolates of ketone 135 to nitroethylene 136 as the key step in the total syntheses of the alkaloids ( )-y-lycorane (139) and ( )-crinane (142) (equation 39) °. Both reactions started from the same Michael donor (135) with nitroethylene (136) as a C-C-NH2 synthon for the construction of aryl-substituted... 

Addition of nitroethylene to the alkoxyenolate generated from 2 affords Michael adduct 226 in 31% yield with a diastereomeric ratio of 85 15 [83]. Likewise, addition of acetone to the same enolate leads to 227 as a 3 1 mixture of anti and syn isomers. Upon distillation the product lactonizes to afford the butyrolactone derivative 228 in 55% yield [79]. 

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... 

When employing nitroethylene as Michael acceptor, tripeptide 15b bearing an additional CH2-group, compared to its parent peptide 15a, showed a more selective performance towards the preparation of p-substituted 5-nitroalcohols (Scheme 13.12b). The conjugate addition products can be readily converted to protected T -amino acids using a Jones reagent followed by Ra-Ni-mediated reduction of the nitro group and final Fmoc-protection. ... 

Despite of the fact that Baylis and Hillman reported the synthesis of a-hydr-oxyethylated nitroethylene through the reaction between nitroethylene and acetaldehyde in the presence of DABCO, nitroalkenes employed as activated olefins in MBH reaction have not received much attention until recently. Prompted by the fact that nitroalkenes have shown superior Michael acceptor abilities, and that the first step in the MBH reaction is the Michael-type addition of the catalyst to substrate, Namboothiri et al. have published a series of papers on nitroalkenes involved the MBH reaction. The MBH reactions between nitroalkenes and various electrophiles such as formaldehyde, activated carbonyl compounds, imines, alkenes and azodicarboxylates " in the presence... 

On the other hand, a dinuclear chiral nickel catalyst, (R)-3, was developed by Mitsunuma and Matsunaga to promote the conjugate addition of a-sub-stituted p-keto esters to nitroethylene. " As shown in Scheme 2.6 the use of 1-10 mol% of this Schiff base dinuclear catalyst in a mixture of EtOAc and toluene as solvent allowed a range of cyclic as well as acyclic p-keto esters to be added to nitroethylene, providing the corresponding chiral Michael products in moderate to almost quantitative yields (73-92%), combined with good to high enantioselectivities of up to 98% ee in the case of cyclic substrates, and... 

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