Michael type addition reaction

The use of carbon nucleophiles in Michael-type addition reactions with pteridine and its derivatives leads to a quite complicated and divergent pattern. These reactions are strongly dependent on the nature of the carbon nucleophile and can be divided into various categories. 

A Michael-type addition reaction of phosphine generated from red phosphorus in concentrated aqueous KOH solution has been noted to provide moderate isolable yields of pure organophosphorus products.27 For example, tris-(2-cyanoethyl)phosphine is produced in 45% isolable yield from acrylonitrile, and tris-(2-[y-pyridyl]ethyl) phosphine oxide is isolated in 40% yield from 4-vinylpyridine under these conditions. Excellent yields of the tertiary phosphine oxide, tris-(2-cyanoethyl)phosphine oxide, have been reported using white phosphorus in absolute ethanol with KOH at ice/salt-bath temperatures.28 A variety of solvent systems were examined for this reaction involving a Michael-type addition to acrylonitrile. Similarly, tris-(Z-styryl)phosphine is produced from phenylacetylene under these conditions in 55% isolated yield. It is noteworthy that this last cited reaction involves stereospecific syn- addition of the phosphine to the alkyne. 

The importance of chiral thiols and thioether linkages in biological systems has prompted intense investigation of the use of chiral amines [see e.g. 5-11] and ammonium salts [see e.g. 12] as agents for asymmetric induction in the Michael-type addition reaction. Considerable success has been achieved using chinchona alkaloids and their A-alkyl derivatives (see Chapter 12). 

A Michael-type addition reaction of substituted ethylenes (39) with 2-phenylindolizines yields 3-substituted indolizines (40) <66AC(R)752). Arylation occurs on treatment of an indolizine with the salt (41) (67TL4321) or with diphenylcyclopropenone (68TL5537), yielding the tetrafluoroborate (42). 

Phenylindolizine undergoes Michael-type addition reactions with 2- and 4-vinylpyridine and with acrylophenone to form 96 and 97,... 

A further frequent complication is that acetylenic esters undergo base and acid-catalyzed self-condensation on standing under normal laboratory conditions, and they will add methanol or similar nucleophiles in Michael-type addition reactions (cf. 4 and 6). Such products are almost invariably present in reaction mixtures obtained from heterocycles. A short account of these products is included as their early recognition in a new investigation can save much time. 

The use of a cyanoethylation procedure (Section 5.13.3, p. 717) or related Michael type addition reactions for the synthesis of functionalised sulphides should be noted as an important preparative route. 

K. Tomioka, Asymmetric Michael-Type Addition Reaction, in Modem Carbonyl Chemistry, Ed. ... 

The cis 2,6 disubstituted piperidinones 49 are formed preferentially in this Michael-type addition reaction (Table 4.7). 

Covalent protein adducts of quinones are formed through Michael-type addition reaction with protein sulfhydryl groups or glutathione. Metabolic activation of several toxins (e.g., naphthalene, pentachlorophenol, and benzene) into quinones has been shown to result in protein quinone adducts (Lin et al., 1997 Rappaport et al., 1996 Zheng et al., 1997). Conversion of substituted hydroquinones such as p-aminophenol-hydroquinone and 2-hromo-hydroquinone to their respective glutathione S-conjugates must occur to allow bioactivation into nephrotoxic metabolites (Dekant, 1993). Western blot analysis of proteins from the kidneys of rats treated with 2-bromo-hydroquinone has revealed three distinct protein adducts conjugated to quinone-thioethers (Kleiner et al., 1998). 

Pteridine Studies. Part XXX. Some Michael-type Addition Reactions of 7-Hydroxypteridine. 

In contrast to maleic hydrazide which gives only AT-substituted monoadducts in the Michael-type addition reactions, cyclic succin-hydrazide can give mono and diaddition products. ... 

Asymmetric Michael Reactions. Asymmetric induction has been observed in Michael-type addition reactions that are catalyzed by chiral amines. The Ai-benzyl fluoride salt of quinine has been particularly successful since the fluoride ion serves as a base and the aminium ion as a source of chirality. Drastic improvements in optical purity (1-23%) have resulted by changing from quinine to the N-benzyl fluoride salt (eq 11). ... 

The homobifunctional cross-linker, glutaraldehyde (GA), can be used for conjugating the molecules containing primary amine groups with amine-terminated PMMA. This is where the formation of Schiff bases with possible rearrangement to a stable product or through a Michael-type addition reaction occurred. The reaction takes place at points of double-bind unsaturation created by polymerization of the GA in solution (121-122) (reaction shown in scheme 8.4). 

Aspartame also can hydrolyze in solution to form a diketopiperazine derivative and can participate in Michael-type addition reactions with olefines susceptible to nucleophilic attack. The products of such interactions, if they occur, will be drug and formulation-specific, and it is likely that their safety characteristics will be unknown. 

Increasing importance has to be attributed to modem tandem (or cascade ) techniques—reaction sequences that can be performed as a one-pot procedure because the first reaction step creates the arrangement of functional groups needed for the second to occur. Schemes 5-7 present some in situ preparations for iminium species, which can then react further with appropriate nucleophiles that are already present (preferably in the same molecule). Most elegantly, in situ generation of iminium ions for tandem processes was performed by a 3,3-sigmatropic (aza-Cope-type) rearrangement (Scheme 5), but also by initial Michael-type addition reactions to vinyl-substituted Atio... 

The Michael-type addition reaction of a carbonucleophile with an activated olefin constitutes one of the most versatile methodologies for carbon-carbon bond formation [1]. Because of the usefulness of the reaction as well as the product, many approaches to the asymmetric Michael-type addition reactions have been reported, especially using chirally modified olefins [2-8]. However, the approach directed towards the enantioselective Michael-type addition reaction is a developing area. In this Chapter, the recent progress of the enantioselective Michael-type addition reaction of active methylene compounds and also organometallic reagents with achiral activated olefins under the control of an external chiral ligand or chiral catalysts will be summarized [9]. 

The first prominent catalytic asymmetric Michael-type addition reaction of an organolithium reagent was shown by the reaction of 1-naphthy[lithium with 1-fluoro-2-naphthylaldehyde imine in the presence of 6 to afford the binaphthyls in high ee. Only catalytic amounts of 6 (0.05 mol%) effects the reaction to give 82% ee, in which an enantioselective Michael-type addition-elimination mechanism is operative (Eq. (12.12)) [31],... 

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