Conjugate addition Michael reaction

Michael reaction conjugate addition of enolate anion onto unsaturated carbonyl... 

Michael reaction. Conjugate addition involving stabilized C-nucleophiles is readily... 

Michael Reaction—Conjugate Addition of Enolate Anions... 

Methacryhc acid and its ester derivatives are Ctfjy -unsaturated carbonyl compounds and exhibit the reactivity typical of this class of compounds, ie, Michael and Michael-type conjugate addition reactions and a variety of cycloaddition and related reactions. Although less reactive than the corresponding acrylates as the result of the electron-donating effect and the steric hindrance of the a-methyl group, methacrylates readily undergo a wide variety of reactions and are valuable intermediates in many synthetic procedures. 

The Michael-type conjugate addition of an alkoxide such as methoxide to an a,p-unsaturated nitrile or aldehyde proceeds in solution quite readily, being complete in 5—10 minutes. In the gas phase however, it was found that reaction (6a) does not occur there is no evidence of the addition product even at the longest trapping times, nor in the unquenched mode. Rather, the sole product observed is due to proton loss from the nitrile, to form a nominal vinyl anion, reaction (6b). 

The majority of the Michael-type conjugate additions are promoted by amine-based catalysts and proceed via an enamine or iminium intermediate species. Subsequently, Jprgensen et al. [43] explored the aza-Michael addition of hydra-zones to cyclic enones catalyzed by Cinchona alkaloids. Although the reaction proceeds under pyrrolidine catalysis via iminium activation of the enone, and also with NEtj via hydrazone activation, both methods do not confer enantioselectivity to the reaction. Under a Cinchona alkaloid screen, quinine 3 was identified as an effective aza-Michael catalyst to give 92% yield and 1 3.5 er (Scheme 4). 

The stereoselectivity of the second and key Michael-type conjugate addition reaction can be rationalized as follows. The conformation of 63 will be restricted to 63-A due to A(l 3) strain between the N-methoxycarbonyl and w-propyl groups in 63-B. Attack of the vinyl anion from the stereoelectronically favored a-axial direction provides the adduct 64 exclusively. It is noteworthy that the stereochemical course of the above reaction is controlled by the stereoelectronic effect in spite of severe 1,3-diaxial steric repulsion between the axial ethyl group at the 5-position and the incoming vinyl anion. This remarkable stereoselectivity can be also explained by Cieplak s hypothesis[31]. On the preferred conformation 63-A, the developing a of the transition state is stabilized by the antiperiplanar donor Gc-h at the C-4 position. 

The Michael reaction is addition of a carbon nucleophile to the /3 position of an a,/3-unsaturated carbonyl compound or its equivalent. It also may be called a 1,4-addition reaction (the carbonyl oxygen is counted as 1 and the )3-carbon as 4). The conjugation of the v bond with thp carbonyl group imparts positive character to the /3 position, making it susceptible to reaction with a nucleophile. The product of this reaction, an enolate ion, also is stabilized by resonance. 

The stereoselectivity of the second and key Michael-type conjugate addition reaction can be rationalized as follows. The conformation of 63 will be restricted to 63-A due to strain between the N-... 

Hetero-Diels-Alder reactions of l-oxa-l,3-butadienes with vinyl ethers, which lead to 3,4-dihydro-2H-pyran derivatives, are synthetically equivalent to Michael type conjugate additions. Wada and coworkers presented the first examples of a catalytic asymmetric intermolecular hetero-Diels-Alder reaction by the use of ( )-2-oxo-l-phenylsulfonyl-3-alkenes 25 and vinyl ethers 26 (Table 3) [25]. 

Michael reaction. Efficient addition of thiols to conjugated carbonyl compounds proceeds in the presence of a catalyst derived from HBF4 adsorbed in silica gel/... 

The normal way to do the cycloadditions is to react the complex with an alkene bearing electron-withdrawing substituents that make the substrate prone to Michael-type conjugate addition. Cyclopentenones illustrate the reaction nicely. 

The addition of active methylene compounds (ethyl malonate, ethyl aoeto-acetate, ethyl plienylacetate, nltromethane, acrylonitrile, etc.) to the aP-double bond of a conjugated unsaturated ketone, ester or nitrile In the presence of a basic catalyst (sodium ethoxide, piperidine, diethylamiiie, etc.) is known as the Michael reaction or Michael addition. The reaction may be illustrated by the addition of ethyl malonate to ethyl fumarate in the presence of sodium ethoxide hydrolysis and decarboxylation of the addendum (ethyl propane-1 1 2 3-tetracarboxylate) yields trlcarballylic acid ... 

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... 

Stabilized anions exhibit a pronounced tendency to undergo conjugate addition to a p unsaturated carbonyl compounds This reaction called the Michael reaction has been described for anions derived from p diketones m Section 18 13 The enolates of ethyl acetoacetate and diethyl malonate also undergo Michael addition to the p carbon atom of a p unsaturated aldehydes ketones and esters For example... 

The 1,4-addition of an enolate anion 1 to an o ,/3-unsaturated carbonyl compound 2, to yield a 1,5-dicarbonyl compound 3, is a powerful method for the formation of carbon-carbon bonds, and is called the Michael reaction or Michael addition The 1,4-addition to an o ,/3-unsaturated carbonyl substrate is also called a conjugate addition. Various other 1,4-additions are known, and sometimes referred to as Michael-like additions. 

The reaction of a cyclic ketone—e.g. cyclohexanone 1—with methyl vinyl ketone 2 resulting in a ring closure to yield a bicyclic a ,/3-unsaturated ketone 4, is called the Robinson annulation This reaction has found wide application in the synthesis of terpenes, and especially of steroids. Mechanistically the Robinson annulation consists of two consecutive reactions, a Michael addition followed by an Aldol reaction. Initially, upon treatment with a base, the cyclic ketone 1 is deprotonated to give an enolate, which undergoes a conjugate addition to the methyl vinyl ketone, i.e. a Michael addition, to give a 1,5-diketone 3 ... 

Enamines react with acceptor-substituted alkenes (Michael acceptors) in a conjugate addition reaction for example with o ,/3-unsaturated carbonyl compounds or nitriles such as acrylonitrile 8. With respect to the acceptor-substituted alkene the reaction is similar to a Michael addition ... 

The reaction of relatively simple starting materials, coumarin 40, piperidone 37 and ammonium acetate, leads in a single step to the complex bridged tetracyclic compound 44. The reaction can be rationalized by assuming formation of the iminc 38 from reaction of 37, with ammonia. Conjugate addition of the eneamine-like tautomer 39 to the excellent Michael acceptor 40 will... 

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