Nucleophilic addition reactions Michael reaction

Acrylonitrile, polymerization, 120 Activity of phase-transfer catalysts Sjj2 reactions, 170-175 weak-nucleophile Sj.Ar reactions, 175-182 Acyltetracarbonyl cobalt compound, cleavage in the carboxyalkylation of alkyl halides, 150 Addition reactions, Michael, catalytic asymmetric, 69,70f... 

NUCLEOPHILIC ADDIHON TO CONJUGATED SYSTEMS CONJUGATE ADDITION AND MICHAEL REACTIONS... 

By 1989 Mukaiyama had already explored the behaviour of phosphonium salts as Lewis acid catalysts. It was possible to show that the aldol-type reaction of aldehydes or acetals with several nucleophiles and the Michael reaction of a,j3-unsatu-rated ketones or acetals with silyl nucleophiles gave the products in good yields with a phosphonium salt catalyst [116]. In addition, the same group applied bisphosphonium salts as shown in Scheme 45 in the synthesis of ]3-aminoesters [117]. High yields up to 98% were obtained in the reaction of A-benzylideneaniline and the ketene silyl acetal of methyl isobutyrate. Various analogues of the reaction parteers gave similar results. The bisphosphonium salt was found to be superior to Lewis acids like TiCl and SnCl, which are deactivated by the resulting amines. 

Reaction of Aniline with Organic Functional Groups. In the absence of catalysis by enzymes or metals, aniline undergoes nucleophilic addition reactions to quinone and other carbonyl groups in humic substances to form both heterocyclic and nonheterocyclic condensation products (9). In aqueous solution, aniline undergoes 1,4-addition (Michael addition) to both 1,2- and 1,4-quinones (10-14). The reaction of aniline with 1,4-benzoquinone, from the oxidation of hydroquinone, and with 4-methyl-1,2-quinone, from the oxidation of 4-methylcatechol, are illustrated here. 

Alkyl phosphonates are prepared smoothly by TMG (1) catalysed aldol-type addition of dialkyl phosphites to ketones and imines under mild conditions [28] (Scheme 4.9). Dialkyl phosphites can also serve as good nucleophiles for Michael addition (phospha-Michael Reaction). 

Nitroalkane also can reacts with carbon-carbon double bonds via Michael nucleophilic addition reaction. And nitroalkanes with a-hydrogen atom can have such reaction under alkaline catalytic conditions. 

In expanding the number Michael/aldol domino processes, chiral N-sulfinimines 27 could be subjected to a magnesium thiolate in the presence of an acrylate 26 to undergo an asymmetric thio-Michael/nucleophilic addition reaction (Scheme 7.4)... 

Michael Addition. The Michael reaction is a typical base-catalyzed reaction used in organic chemistry to form a C—C bond. It is usually a consecutive side reaction accompanying the base-catalyzed synthesis of a, -unsaturated ketones, aldehydes, nitriles, or carbo lic acid derivatives. The reaction between an Q ,)S-unsaturated compoimd and an activated methylene compoimd is known as the Michael addition Scheme 9. The reaction is the nucleophilic addition of a car-banion intermediate to the ft carbon of the C—C double bond in the conjugated system (49) without releasing a water molecule. The carbanion is provided by the activated methylene compoimd, and contrarily to the Knoevenagel condensation the product retains the substituents of both reactant molecules. 

Aldehydes and ketones that possess a,(3 unsaturation are susceptible to nucleophilic attack at the (3 position. This reaction is called a conjugate addition, 1,4-addition, or Michael reaction. 

Three-component reaction of 2-ethynylaniline, sulfonyl azide, and nitroolefin also could lead to polysubstituted indole derivatives in moderate to good yields with CuBr catalyst. The reaction conditions are extremely mild and various polysubstituted indoles were obtained successfully. Initially, a triazole intermediate was formed from alkyne and sulfonyl azide in the presence of CuBr and triethy-lamine. It could convert into reactive ketenimine by the ring-opening rearrangement. Subsequently intramolecular nucleophilic addition, intermolecular Michael addition, and tautomerization could lead to the desired polysubstituted indoles [49] (Scheme 8.20). 

A synthetically useful reaction known as the Michael reaction, or Michael addition, involves nucleophilic addition of carbanions to a p unsaturated ketones The most common types of carbanions used are enolate 10ns derived from p diketones These enolates are weak bases (Section 18 6) and react with a p unsaturated ketones by conjugate addition... 

Aqueous ammonia and acryUc esters give tertiary amino esters, which form the corresponding amide upon ammonolysis (34). Modem methods of molecular quantum modelling have been appHed to the reaction pathway and energetics for several nucleophiles in these Michael additions (35,36). 

Addition Reactions. The addition of nucleophiles to quinones is often an acid-catalyzed, Michael-type reductive process (7,43,44). The addition of benzenethiol to 1,4-benzoquinone (2) was studied by A. Michael for a better understanding of valence in organic chemistry (45). The presence of the reduced product thiophenyUiydroquinone (52), the cross-oxidation product 2-thiophenyl-1,4-benzoquinone [18232-03-6] (53), and multiple-addition products such as 2,5-(bis(thiophenyl)-l,4-benzoquinone [17058-53-6] (54) and 2,6-bis(thiophenyl)-l,4-benzoquinone [121194-11-4] (55), is typical ofmany such transformations. 

Nucleophilic Substitution Reactions. Many of the transformations reali2ed through Michael additions to quiaones can also be achieved usiag nucleophilic substitution chemistry. In some iastances the stereoselectivity can be markedly improved ia this fashion (100), eg, ia the reaction of ben2enethiol with esters (R = CH C O) and ethers (R = 3) 1,4-naphthoquiaones. 2-Bromo-5-acetyloxy-l,4-naphthoquiQone [77189-69-6J, R = Br, yields 75% of 2-thiophenyl-5-acetyloxy-l,4-naphthoquinone [71700-93-1], R = SC H. 3-Bromo-5-methoxy-1,4-naphthoquinone [69833-10-9], R = Br, yields 82% of 3-thiophenyl-5-methoxy-l,4-naphthoquinone [112740-62-2] R = SC H. ... 

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 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. 

Unsubstituted 2,1-benzisoxazoles undergo C(3)-proton abstraction with base to give an intermediate iminoketene which can undergo further reaction with nucleophiles. However, alternative Michael addition pathways are possible and these have been discussed (81AHC(29)l,p.56). 

Michael addition reactions, 3, 279 with carbon nucleophiles, 3, 288 reactions... 

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