Formation by Michael Addition

Dicarbonyl compounds are widely used in organic synthesis as activated nucleophiles. Because of the relatively high acidity of the methylenic C—H of 1,3-dicarbonyl compounds, most reactions involving 1,3-dicarbonyl compounds are considered to be nucleophilic additions or substitutions of enolates. However, some experimental evidence showed that 1,3-dicarbonyl compounds could react via C—H activations. Although this concept is still controversial, it opens a novel idea to consider the reactions of activated C H bonds. The chiral bifunctional Ru catalysts were used in enantioselective C C bonds formation by Michael addition of 1,3-dicarbonyl compounds with high yields and enantiomeric excesses. ... 

IV. C-C BOND FORMATION BY MICHAEL ADDITION OF METAL ENOLATES A. Introduction... 

Scriban C, Kovacik I, Glueck DS (2005) A protic additive suppresses formation of byproducts in platinum-catalyzed hydrophosphination of activated olefins. Evidence for P-C and C-C bond formation by Michael addition. Organometallics 24 4871-4874... 

Vinylogous amides undergo reduction with lithium aluminum hydride, by Michael addition of hydride and formation of an enolate, which can resist further reduction. Thus -aminoketones are usually produced (309, 563,564). However, the alternative selective reduction of the carbonyl group has also been claimed (555). 

The mechanism is presumed to involve a pathway related to those proposed for other base-catalyzed reactions of isocyanoacetates with Michael acceptors. Thus base-induced formation of enolate 9 is followed by Michael addition to the nitroalkene and cyclization of nitronate 10 to furnish 11 after protonation. Loss of nitrous acid and aromatization affords pyrrole ester 12. 

After reduction of the nitro function of the porphyrin, the porphyrinamine intermediate can be reacted with z./l-unsaturated carbonyl compounds to yield porphyrins with a fused pyridine ring, which is formed by Michael addition, imine formation and dehydrogenation. 

The starting Fischer-type carbene complexes 1 were obtained by Michael addition of dimethylamine to the carbon-carbon triple bond of the corresponding ethoxy-(phenylethynyl)carbenes. In this regard, de Meijere and co-workers observed that the reactions of several primary and secondary amines with this sort of carbenes, in particular chromium derivatives 3 containing bulky substituents at the terminal carbon of the acetylenic unit, result in formation of the aminoallenylidene derivatives 5 as by-products of the expected Michael adducts 4 (Scheme 2) [20-24]. 

Cyclopropane ring formation has been brought about by Michael addition initiated ring closure (sometimes called MIRC). The reaction of methyl 4-bromocrotonate (3) with different nucleophiles either gives the SN2-displacement product 4 or the Michael addition intermediate 5 which finally forms the cyclopropane carboxylate 697 (the configuration of 6 has not been determined). This reaction has been studied with different nucleophiles in the solvent systems tetrahydrofuran-HMPA (20 1) and tetrahydrofuran the bromocrotonate 3 was reacted with 1 equivalent of a 1 M solution of the lithium enolates at —78 for 12 h at room temperature97. 

The reaction sequence depicted i.e., the in situ alkylation of an a-anion created by Michael addition, is an important method for the formation of an enolate of an unsaturated carbonyl compound17,18. 

Electron-deficient alkenes, either these with conjugating substituents or of enones, undergo Michael-like additions with regiospecific introductions of the nucleophiles, and this approach has been successful for the formation of cyclopropyl derivatives—notably from some nucleosides. An example involves the addition of the anion of bis(phenylsulfonyl)methane to the phenylselenone 173 which gives the adduct 174 in 35% yield. This reaction presumably occurs by Michael addition to C-2 followed by Sn2 ring-closure reaction at C-3 with displacement of phenylselenic acid. Reductive desulfonylation affords the 2,3,-dideoxy-2,3 -cyclopropayuridine 175.199... 

In the synthesis of (+)-dihydrocorynantheol (92) by Kametani et al.,56a the tetracyclic system (93) was constructed by Michael addition of an enamine, derived from the dihydro-/ -carboline (76), to dimethyl 3-methoxyallylidenemalonate, with closure of the lactam ring (Scheme 15). The product (93) was then converted (by unexceptional methods), via the lactam aldehyde (94), into ( )-dihydrocoryn-antheol, the normal stereochemistry in which follows from its mode of formation. 

Formation of a cyclohexenone ring by condensation of methyl vinyl ketone (MVK) or a substituted MVK derivative with a ketone. Robinson annulation proceeds by Michael addition to MVK, followed by an aldol condensation with dehydration, (p. 1088)... 

Nakamura, S., Inagaki, J., Kudo, M., Sugimoto, T, Ohara, K., Nakajima, M. and Hashimoto, S., 2002. Studies directed toward the total synthesis of pinnatoxin A synthesis of the 6,5,6-dispiroketal (BCD ring) system by double hemiketal formation/hetero-Michael addition strategy. Tetrahedron 58, 10353-10374. 

It has been shown that benzils (323) react with Michael addition acceptors (324) in the presence of a catalytic amount of cyanide ion to yield 1,4-diketones (325). The authors proposed that (325) are produced through the formation of the O-aroylmandelonitrile anion, followed by Michael addition and rearrangement of the aroyl group with decyanation (see Scheme 77). The mechanism of the base-catalysed ring fission of 2,2-dihydroxyindane-l,3-diones has been investigated and the pathway set out in Scheme 78 has been proposed for the transformation. The base-catalysed ring... 

V-carboxyethyl-substiluted macrocycles have been prepared by nucleophilic substitution using 2-bromopropionic acid, and by Michael addition of acrylic acid, acrylonitrile, or acrylamide, followed by hydrolysis. The formation constants with cations are lower than for carboxymethyl analogues and structures of lanthanide compounds are generally -carboxylato polymeric, often with the nitrogen atoms not coordinated. 

When methyl 2-(trimethylsiloxy)-2-vinylcyclopropanecarboxylates 8 and 10 were reacted with C —H acidic agents such as malonic acid derivatives or nitroalkanes, in the presence of the catalyst Triton B, ring opening and formation of Michael addition products occurred. The methoxide is thought to initiate the ring opening by desilylation and generation of the C-nucleophile. 

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