Michael addition/reactions

Chemists usually learn about reactions according to fiinctional groups for example, How can I make an aldehyde and what reactions are known for aldehydes " This is clearly not a very good starting point for classifying reactions. The poor state of affairs in the definition of reaction types is further quite vividly illustrated by the fact that many chemical reactions are identified by being named after their inventor Diels-Alder reaction, Michael addition, Lobry-de Bruyn-van Ekenstein rear-... 

The method was applied to the synthesis of (-t-)-l9-nortestosterone by the following sequence of reactions. Michael addition of the bisannulation reagent 124 to the optically active keto ester 129 and decarboxylation afforded 130, and subsequent aldol condensation gave 131. Selective Pd-catalyzed oxidation of the terminal double bond afforded the diketone 132 in 78% yield. Reduction of the double bond and aldol condensation gave ( + )-19-nortestosterone (133)[114]. 

From the foregoing it can be seen that the nitro group can be activated for C-C bond formation in various ways. Classically the nitro group facilitates the Henry reaction, Michael addition, and Diels-Alder reaction. Komblum and Russell have introduced a new substitution reaction, which proceeds via a one electron-transfer process The Spj l reactions have... 

Chiral PTC has been used effectively for making intermediates for drugs. Dolling and coworkers have used 8-R, 9-5, N-(p-trifluoromethylbenzyl) cinchonium bromide to carry out an important asymmetric alkylation, giving 95% ee (Starks, 1987). Nucleophilic epoxidations of enones, Darzens reaction, Michael additions, etc. are some examples of reactions rendered asymmetric through chiral PTCs (Nelson, 1999). 

The conversion of primary or secondary nitro compounds into aldehydes or ketones is normally accomplished by use of the Nef reaction, which is one of the most important transformations of nitro compounds. Various methods have been introduced forthis transformation (1) treatment of nitronates with acid, (2) oxidation of nitronates, and (3) reduction of nitroalkenes. Although a comprehensive review is available,3 important procedures and improved methods published after this review are presented in this chapter. The Nef reaction after the nitro-aldol (Henry reaction), Michael addition, or Diels-Alder reaction using nitroalkanes or nitroalkenes has been used extensively in organic synthesis of various substrates, including complicated natural products. Some of them are presented in this chapter other examples are presented in the chapters discussing the Henry reaction (Chapter 3), Michael addition (Chapter 4), and Diels-Alder reaction (Chapter 8). 

A fundamentally different approach to the synthesis of 3-pyrrolines is evidenced in the annulation in Eq. 13.50 [58]. Ethyl 2,3-butadienoate 150 reacts with N-sulfony-limine 151 in the presence of triphenylphosphine under very mild conditions to give JV-protected 3-pyrroline 152 in 90% yield. The mechanism that has been postulated is related to that of the Baylis-Hillman reaction. Michael addition of triphenylphosphine to the allenyl ester generates a zwitterion that combines with the imine to give 153 in a non-concerted process. This is followed by ring closure, proton exchange and expulsion of triphenylphosphine to give 152. This annulation is successful only for aromatic or cinnamyl imines [59]. 

Keywords 1,3-Dicarbonyls, Biginelh reaction, Hantzsch reaction, Heterocyclic chemistry, Knoevenagel condensation, Mannich reaction, Michael addition, Multi-component reactions... 

Scheme 4.15 Examples of promiscuous enzymatic reactions conducted with the oxyanion hole of Candida antarctica lipase B (a) the aldol reaction [104] (b) the conjugate addition reaction (Michael addition) [105] (c) the epoxidation reaction [106],...

The reaction of 75 with 76 in the presence of nitromethane to ultimately produce 77 is thought to proceed by an analogous mechamsm <99TL4023, 99TL4027>. The authors noted that this tandem Nef reaction/Michael addition produced 77 in a single step with sonication. 

Keywords caclohexanone derivative, a,/ -unsaturated carbonyl compound, phase transfer reaction, Michael addition, 1,5-dicarbonyl compound... 

Although the number of Diels-Alder cycloadditions with open-chain and alicyclic dienes is very large, the number of examples with aromatic heterocyclic compounds is relatively small. The introduction of a vinyl group as a substituent onto a heterocycle increases the number of possibilities of reaction. This new possibility, however attractive for synthetic purposes, is successful, with a few exceptions, only with 7r-excessive five-membered heterocyclic derivatives. As is usual in this kind of reaction, Michael additions, ene reactions, [2 + 2]-cycloadditions, and polymerization compete with the Diels-Alder cycloaddition. 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

Review. Davies has reviewed use of the chiral iron auxiliary [CpFe-(CO)P(C6H5)3] for effecting asymmetric reactions of an acyl group, including alkylation, aldol reactions, Michael additions. 

Because of the stability of iron tricarbonyl diene complexes, conjugated dienals are protected from polymerization when complexed, while other reactions can be carried out at the aldehyde functionaUty. A number of synthetically attractive nucleophilic transformations of the aldehyde can be performed on these complexes. These include, aldol reactions, Michael additions, reactions with organozinc, -silicon, -boron, and -tin... 

Addition reactions (Michael addition) can occur with a,) -unsaturated aldehydes and ketones, in competition with normal 1,2-addition [Eq. (1)] ... 

The nitro group activates aliphatic systems and makes possible a number of addition reactions such as aldoiic addition of aldehydes (Henry reaction). Man-nich reaction, Michael addition, Diels - Alder reaction, for example (I55. ... 

Reduction of the double bond Polymerization Nitroacctylcncs Polynitro aliphatic compounds Nitration of hydrt>carbons Substitution of halogen Electrolytic methtnls Addition reaction Michael addition Diels-Aider addition Oxidative dimerization a. u>-Dinitroalkanes gcm-Dinitroalkanes I rinitromethane (nitroform) derivatives Properties of nitroform Manufacture of nitroform... 

Microencapsulated Sc(OTf)3 has shown considerable promise for both batch and flow reactions in those procedures in which the reaction was recirculated through columns containing the reagent. This reagent was found to be more reactive than the monomeric Lewis acid. One example is the TMS-mediated Michael reaction shown in Figure 3.25. Microencapsulated Sc(OTf)3 was also found to be useful for Mannich reactions, Michael additions, and Friedel-Crafts—like acylations [51]. 

The use of these materials in a range of reactions [isomerization of alkenes and alkynes, C—C bond formation, aldol condensation, Knoevenagel condensation, nitroaldol reactions, Michael addition, conjugate addition of alcohols, nucleophilic addition of phenylacetylene, nucleophilic ring opening of epoxides, oxidation reactions, Si—C bond formation, Pudovik reaction (P—C bond formation) and synthesis ofheterocycles] have been discussed in detail by Ono [248], as well as in the other cited reviews. We will thus discuss here only selected examples. 

To date, no known bisindole alkaloid has been shown to be only an artefact. In addition, no experimental evidence exists which undermines the assumption that bisindole alkaloids are actually formed from the completed monomeric partners. Support for this idea is derived from the kind of reactions apparently necessary to effect such dimerisations which are known biogenetic processes amine-aldehyde condensations, Mannich reactions, Michael additions, Friedel-Craft type condensations, Diels-Alder type processes, radical coupling etc. The observation that the skeletal distribution amongst monomeric alkaloids is reflected throughout the dimeric series lends further support. 

Iron chiral auxiliary for asymmetric aldol reaction, Michael addition, p-amino acid and p-lactam synthesis. 

In conclusion, chiral heterobimetallic lanthanoid compexes LnMB, which were recently developed by Shibasaki et al., are highly efficient catalysts in stereoselective synthesis. This new and innovative type of chiral catalyst contains a Lewis acid as well as a Bronsted base moiety and shows a similar mechanistic effect as observed in enzyme chemistry. A broad variety of asymmetric transformations were carried out using this catalysts, including asymmetric C-C bond formations like the nitroaldol reaction, direct aldol reaction, Michael addition and Diels-Alder reaction, as well as C-0 bond formations (epoxidation of enones). Thereupon, asymmetric C-P bond formation can also be realized as has been successfully shown in case of the asymmetric hydrophosphonylation of aldehydes and imines. It is noteworthy that all above-mentioned reactions proceed with high stereoselectivity, resulting in the formation of the desired optically active products in high to excellent optical purity. 

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