Michael addition reaction formation

The formation of Zj -adducts—e.g. 8 by a consecutive Michael addition reaction, is observed in some cases. This reaction is formulated as a 1,4-addition of a second molecule of the CH-acidic starting material 2 to the initially formed a ,/3-unsaturated carbonyl compound 3 ... 

The intramolecular Michael addition11 of a nucleophilic oxygen to an a,/ -unsaturated ester constitutes an attractive alternative strategy for the synthesis of the pyran nucleus, a strategy that could conceivably be applied to the brevetoxin problem (see Scheme 2). For example, treatment of hydroxy a,/ -unsaturated ester 9 with sodium hydride furnishes an alkoxide ion that induces ring formation by attacking the electrophilic //-carbon of the unsaturated ester moiety. This base-induced intramolecular Michael addition reaction is a reversible process, and it ultimately affords the thermodynamically most stable product 10 (92% yield). 

In addition to a-additions to isocyanides, copper oxide-cyclohexyl isocyanide mixtures are catalysts for other reactions including olefin dimerization and oligomerization 121, 125, 126). They also catalyze pyrroline and oxazoline formation from isocyanides with a protonic a-hydrogen (e.g., PhCH2NC or EtOCOCHjNC) and olefins or ketones 130), and the formation of cyclopropanes from olefins and substituted chloromethanes 131). The same catalyst systems also catalyze Michael addition reactions 119a). 

Combinatorial solid-phase synthetic methodologies have been used extensively in drug development [8]. A new solid-phase synthesis of 2-imidazolidones has been discovered by Goff, based on a domino aminoacylation/Michael addition reaction [9]. Thus, when immobilized amine 10-26 (HMPB-BHA resin) was treated with phenylisocyanate in the presence of triethylamine, a smooth formation of 2-imida-zolidone took place. Acid-catalyzed removal from solid phase provided 10-27 in good yield (Scheme 10.6). 

Other routes to piperidines involving 1,4-addition reactions include the incorporation of a Michael addition reaction as the piperidine ring formation step in the total synthesis of Histrionicotoxin <06JA12656> and the use of an intramolecular 1,4-addition, 6-endo-dig ring... 

The Michael addition reaction of the serine-derived oxazolidine 326 with ethyl acrylate gave two products. The major product of the reaction was found to be the bicyclic compound 327, which was formed in 27% yield, accompanied by the unsaturated ester 328. The Dess-Martin oxidation of 327 resulted only in formation of the elimination product, the 7,7a-dihydro-177, 377-pyrrolo[l,2-r ]oxazole 328 (Scheme 46) <2001JOC7555>. 

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

The formation of -adducts—e.g. 8 by a consecutive Michael addition reaction,... 

The synthetic methods which are illustrated in this section are (a) the formation of symmetrical 1,4-diketones from 1,3- (or / -)keto esters (Expt 5.104), and (b) a Michael addition reaction involving nitroalkanes and a, /f-unsaturated ketones (Expt 5.105). The synthesis of symmetrical 1,4-diketones from the sodio derivatives of /f-keto esters, or their mono-alkyl derivatives, by treatment with iodine [Method (a)], may be formulated in the following general manner. 

Nucleophile addition to a quinone methide is formally a Michael addition reaction.153 However, an important difference between 1,6-addition of nucleophiles to / -quinone methides and conventional Michael addition reactions is the aromatization of the cyclohexadiene ring that accompanies this addition. The effect of aromatic ring formation on the thermodynamic driving force for 1,6-addition of water to p-1 has been evaluated by comparing the thermodynamics... 

Consequently, the Michael addition reaction of sugar thiol proceeds smoothly with the formation of P- (l-2)-2,3-dideoxy-2-C-nitromethyl-thio-disacharides in 63-70 % yield (scheme 6). 

The use of C-H bonds is obviously one of the simplest and most straightforward methods in organic synthesis. From the synthetic point of view, the alkylation, alkenylation, arylation, and silylation of C-H bonds are regarded as practical tools since these reactions exhibit high selectivity, high efficiency, and are widely applicable, all of which are essential for practical organic synthesis. The hydroacylation of olefins provides unsymmetrical ketones, which are highly versatile synthetic intermediates. Transition-metal-catalyzed aldol and Michael addition reactions of active methylene compounds are now widely used for enantioselective and di-astereoselective C-C bond formation reactions under neutral conditions. 

An interesting feature the crystals of 1-Cu is that they show triboluminescent behaviour. Compound 1-Cu has been applied successfully as a catalyst in the enantioselective Michael addition reaction involving a variety of substrates and Grignard reagents (eq 6). The addition reaction proceeds with excellent chemical yields, and enantiomeric excesses of up to 70% have been reported. It was shown that the (/ )-catalyst gives rise to the formation of (5)-products. ... 

The Michael addition reaction in water suspension medium is also applicable to carbon-carbon bond formation. A mixture of 70a, methyl acetylacetate (76), 72 and water was stirred for 5 h at room temperature, then the reaction product was filtered and dried to give the addition product 77 in 98% yield [34]. Although a similar solvent-free Michael addition reaction of 70a with diethyl malonate at 60 °C has been reported, organic solvent was still necessary to isolate the product from the reaction mixture [36]. 

A mechanism for the formation exo-5-morpholinobicyclo[2.2.1]heptan-2-one via a ho-moenolate ion intermediate in a Michael-type addition reaction has been proposed. Michael addition reactions involving secondary amines and a,)S-unsaturated carbonyl compounds have been reported, but this was the first example of such a reaction involving the ho-moenolate ion. ... 

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