Michael functions reaction

Micha.elAdditions. The reaction of a bismaleimide with a functional nucleophile (diamine, bisthiol, etc) via the Michael addition reaction converts a BMI building block into a polymer. The non stoichiometric reaction of an aromatic diamine with a bismaleimide was used by Rhc )ne Poulenc to synthesize polyaminobismaleimides as shown in Figure 6 (31). 

The Michael addition reaction of amines and thiols with bismaleimides or functionalized monomaleimides is a versatile tool ia the synthesis of chain-extended maleimide-terroinated prepolymers. These prepolymers generally are soluble ia organic solvents from which they can be processed to prepreg and molded to high quaUty, void-free laminates. 

Another important feature of the Nef reaction is the possible use of a CH-NO2 function as an umpoled carbonyl function. A proton at a carbon a to a nitro group is acidic, and can be abstracted by base. The resulting anionic species has a nucleophilic carbon, and can react at that position with electrophiles. In contrast the carbon center of a carbonyl group is electrophilic, and thus reactive towards nucleophiles. 1,4-Diketones 4 can for example be prepared from a-acidic nitro compounds by a Michael additionfNef reaction sequence " ... 

A sequence of straightforward functional group interconversions leads from 17 back to compound 20 via 18 and 19. In the synthetic direction, a base-induced intramolecular Michael addition reaction could create a new six-membered ring and two stereogenic centers. The transformation of intermediate 20 to 19 would likely be stereoselective substrate structural features inherent in 20 should control the stereochemical course of the intramolecular Michael addition reaction. Retrosynthetic disassembly of 20 by cleavage of the indicated bond provides precursors 21 and 22. In the forward sense, acylation of the nitrogen atom in 22 with the acid chloride 21 could afford amide 20. 

Michael addition reactions are particularly useful when linear aliphatic bis-nitramines are used because the products contain two terminal functional groups like in the diester (182). The terminal functionality of such products can be used, or modified by simple functional group conversion, to provide oligomers for the synthesis of energetic polymers such oligomers often use terminal alcohol, isocyanate or carboxy functionality for this purpose. 

Group-transfer polymerizations make use of a silicon-mediated Michael addition reaction. They allow the synthesis of isolatable, well-characterized living polymers whose reactive end groups can be converted into other functional groups. It allows the polymerization of alpha, beta-unsaturated esters, ketones, amides, or nitriles through the use of silyl ketenes in the presence of suitable nucleophilic catalysts such as soluble Lewis acids, fluorides, cyanides, azides, and bifluorides, HF. ... 

The addition to a, -unsaturated esters is usually difficult. However, under appropriate conditions, the 1,4-addition of diorganozincs to enoates is possiblc As mentioned above, Michael-addition reactions can also be catalyzed by Ni(II) salts . The 1,4-addition of functionalized organozinc iodides to enones in the presence of Ni(acac)2, a diamine as ligand and TMSCl provides, after hydrolysis, the Michael adducts in satisfactory yields . 

Tomalia et al. (5) develop a synthetic method for preparing functionalized dendritic compositions having high thermal stability that did not undergo a reversible Michael addition reaction. 

The Michael addition reaction of dimercaptodiphenylether with N-(3-ethynyl phenyl) maleimide allowed the synthesis of ethynyl-terminated imido-thioether as shown in Fig. 50 (139). This acetylene terminated imidothioether was blended with acetylene terminated polyarylene ether oligomers of different molecular weights and tested as composite resins (140). Blends of functionalized thermoplastics such as the acetylene terminated polyarylene ethers with brittle high-Tg imide resins are finding increased attention for tough high-Tg composites. 

A variety of nucleophilic agents can be used propanedinitrile, 3-oxo-butanoate esters, and cyanoethanoate esters all form relatively stable car-banions and function well in Michael addition reactions. Obviously, if the carbanion is too stable, it will have little or no tendency to attack the double bond of the a./8-unsaturated acid derivative. The utility of the Michael addition for preparing 1,5-dicarbonyl compounds is illustrated by the examples in Exercise 18-49. 

A bioxantracene (-)-ES-242-4 (46) was isolated from the culture broth of Verticillium sp. in 1992 as one of eight antagonists for the 7V-methy 1-D-aspartate (NMDA) receptor (7<5). These novel natural products are reported to inhibit the PH]thienyl cyclohexylpiperidine binding to rat crude synaptic membranes, and therefore, are of potential therapeutic interest for die treatment of neurodegenerative diseases. (-)-ES-242-4 (46) is structurally remarkable having an axially chiral binaphthalene core that is adorned with two pyrans of the same absolute chirality. Our interest in the construction of densely functionalized naphthopyran ring systems, via tandem Michael-Dieckmann reactions, promoted us to attempt the first stereocontrolled total synthesis of (-)-ES-242-4 (46) (19). 

Novel methods for functionalizing piperidines at the 3- and 4-positions were also introduced. Mete and co-worker synthesized 3-diazo-piperidin-2-one and characterized its reactivity in transition-metal catalyzed reactions, particularly H-X insertion reactions and cyclopropanation reactions <02T3137>. Christoffers and co-workers developed an asymmetric Michael addition reaction with a chirally modified 4-piperidone-enamine. They were able to create a quaternary carbon center in >95% de and elaborate the compound on through classical means to the functionalized piperidine 107 (Scheme 21) <02EJ01505>. 

For the asymmetric synthesis of the 2-substituted chromane 7 via the intramolecular Michael addition reaction of 6, Merschaert et al. also employed natural cinchona alkaloids such as HCD as catalysts (Scheme 9.3) [3]. Here again, the 9-0 functionalization and dehydroxylation of the natural alkaloid showed a large negative effect, indicating that the presence of the 9-OH group is needed to achieve both good kinetics and enantioselectivity. Moreover, C3 modifications of this parent alkaloid did not lead to any significant improvement in the results in terms of the enantioselectivity and catalytic activity. 

By employing the primary amine catalyst 160, Zhong and coworkers developed the tandem Michael-Henry reaction of ketones with nitroalkenes to provide highly functionalized chiral hexanes and pentanes with high diastereo- and enantioselec-tivity [49]. The selected examples depicted in Scheme 9.56 show that, in the presence of 160 (10-15 mol%), various Michael donors and nitroalkenes smoothly underwent the tandem reaction with almost quantitative yield and extremely high enantios-electivity with the complete diastereoselectivity of the products. Further details of this reaction can be seen in Section 10.4. 

Chen and coworkers have reported a new domino Michael-Michael addition reaction between a,a-dicyanoalkene [26] derived from cyclohexanone and benzyli-deneacetone, resulting in a stepwise [4 + 2]-type cycloaddition to afford almost enantiopure bicyclic adduct 15. In contrast to the completely inert function of secondary ammonium salt, a primary amine, 9-amino-9-deoxyepiquinine lo [27], in combination with trifluoroacetic acid, was found to be highly efficient in the activation of the a, 3-unsaturated ketone by tandem iminium-enamine catalysis (Scheme 10.21) [28],... 

The Michael addition reaction is commonly recognized as one of the most important carbon-carbon bond-forming reactions in organic synthesis, and major efforts have been made to develop efficient catalytic systems for this type of transformation. In particular, the Michael addition of a carbon nucleophile to nitroalkenes is a useful synthetic method for the preparation of nitroalkanes [76], which are versatile synthetic intermediates owing to the various possible easy transformations of the nitro group into other useful functional groups, such as amino groups and nitrile oxides. 

The enone (3) serves as new convenient building block for a stereoselective functionalization reaction, particularly as a Michael addition reaction acceptor (Scheme 1). 

Another category of reactive enones is 4-deoxy-l,2-0-isopropylidene-L-glycero-pent-4-enopyrano-3-ulose, originally synthesized by Klemer and Jung (25) and currently explored by us as an extremely useful new chiral building block for stereoselective functionalization reactions, especially as Michael addition acceptors (Scheme 6). 

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