Conjugate addition reactions Methyl acrylate

In a much more recent report, conveniently O-protected a-hydroxymethyl aryl ketones were also successfully employed as Michael donors in the conjugate addition to methyl acrylate and acrylonitrile using a cinchonine-based ammonium salt as catalyst. Bis-quinidine-based ammonium salt 105 has also shown to be useful in the reaction of cyclic p-ketoesters to methyl and ethyl acrylate. ... 

Cyclopropanecarboxylic esters have been prepared, in 75—86 % yield, by intramolecular alkylation of 4-chloroalkyl esters, using phase-transfer catalysis. Monoalkylation of nitro-alkenes by acrylic esters occurs in a controlled manner if a two-phase system is used, to give products of Michael addition in 45—65 % yield for five examples. An interesting variant on this reaction involves the generation of the a-nitro-carbanion by conjugate reduction of a nitroalkene with sodium borohydride followed by its conjugate addition to methyl acrylate yields of 62—95% are reported for five cases (Scheme 39). ... 

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 photoaddition of alkanes onto electron-poor alkynes (e.g., propiolate or acetilendicarboxylate esters) can be accomplished by a radical conjugate addition reaction [7]. Radicals have been generated either via hydrogen abstraction from cycloalkanes or via electron transfer from 2-alkyl-2-phenyl-l,3-dioxolanes. In the first case, the irradiation was pursued on an alkane solution of an aromatic ketone (used as the photomediator) and the alkyne. Under these conditions, methyl propiolate was alkylated upon irradiation in the presence of 4-trifluoromethylacetophenone to form acrylate 48 in 97% yield (E/Z= 1.3 1 Scheme 3.31) [78]. 

In a synthesis of the tricychc skeleton of FR901483 (45), Bonjoch and Sole reported a TMG (3) promoted conjugate addition reaction of nitroalkane to methyl acrylate. Reaction of methyl acrylate (40) and nitro acetal 41 [9,10], obtained from Diels-Alder reaction between nitroethylene and 2-(trimethylsilyloxy)-l,3-butadiene, gave nitro ester 42 in 71% yield. The ester 42 was further converted to the spiro compound 43, and a palladium promoted cyclization reaction led to the azatricyclic skeleton 44 (Scheme 7.7). 

Asymmetric conjugate addition reactions of carbonyl compounds with a, -unsaturated systems are known. The simple amine a-methylbenzylamine 68 acts as both the activator (to give the imine and hence the enamine required for alkylation) and as the chiral auxiliary to effect neutral asymmetric conjugate-addition reactions. " Thus, condensation of (5)-a-methylbenzylamine 68 with 2-methylcyclohexanone, followed by addition of methyl acrylate (and hydrolysis of the product imine), gave the 2,2-disubstituted cyclohexanone 69 with high enantiomeric purity (1.78). 

The first step in a one-pot formation of a phenanthrene ring system from an enantiomericaUy pure rhenium-bound naphthalene is a TBDMS triflate-promoted Michael addition to 3-penten-2-one (eq 26). Electron-rich rhenium-bound naphthalenes also undergo TBDMS triflate-promoted conjugate addition reactions to less-activated Michael acceptors such as methyl acrylate, leading to the formal Diels-Alder cycloaddition product of naphthalene with this dienophile. ... 

Cram s pioneering work had a significant impact in the design of new chiral crown ethers as phase-transfer catalysts. Koga synthesized a series of C2-symmetric chiral crown ethers 2-4 from optically active diols, and systematically investigated their performance in the asymmetric conjugate addition of methyl phenylacetate to methyl acrylate [8]. Recently, a novel BINOL-based aza-crown ether 5 was developed by Jaszay et al. [9], which was proved to be effective for the asymmetric conjugate addition reaction. Takizawa and coworkers applied a chiral spiro crown ether 6 to the asymmetric benzylation... 

In recent years, there has been increased recognition that water is an attractive medium for organic reactions from the environmental point of view. The Michael addition of various nitroalkanes to conjugated enones can be performed in NaOH (0.025 M) and in the presence of cetyltrimethylammonium chloride (CTAC1) as cationic surfactant in the absence of organic solvents (Eq. 4.109).146 The Michael addition of nitromethane to methyl acrylate is carried out in water using NaOH as a base to give the mono adduct (Table 4.2).147... 

Michael Reaction. 5(47/)-Oxazolones undergo base-catalyzed conjugate addition to activated unsaturated compounds to afford the corresponding C-4 Michael adducts. For example, base-catalyzed addition of a 4-monosubstituted-5(4//)-oxazolone 157 to methyl propiolate yields a mixture of diastereomeric methyl 3-(5-oxo-2-phenyl-2-oxazolin-4-yl)acrylates 158. Hydrolytic ring opening of 158 and subsequent oxidation with lead tetraacetate affords 3-acylacrylates 160... 

To the extent that the enolate resulting from conjugate addition at the (3-carbon can be stabilized, the rate of this reaction pathway is enhanced. For example, (3-Michael additions are observed for MVK, acrolein, and acetylenic electrophiles even without the presence of a Lewis acid. Furthermore, MVK reacts with the 2,5-dimethylpyrrole complex (22) to form a considerable amount of (3-alkylation product, whereas only cycloaddition is observed for methyl acrylate. The use of a Lewis acid or protic solvent further enhances the reactivity at the (3-position relative to cycloaddition. While methyl acrylate forms a cycloadduct with the 2,5-dimethylpyrrole complex (22) in the absence of external Lewis acids, the addition of TBSOTf to the reaction mixture results in exclusive conjugate addition (Tables 3 and 4). 

A large number of aza crowns are made by these routes. Stepwise addition of CH2CH2NHTs groups occurs readily by reaction of the appropriate tolu-enesulfonamide with 2-bromoacetamide followed by borane reduction and A-tosylation. If a trimethylene spacer is desired, then reaction of the tosyla-mide with acrylonitrile followed by reduction and tosylation gives good yields of the desired product (Scheme 1.2). An example of such a sequence is provided by the synthesis of the symmetrical [24]-N6 cycle, 4 (Scheme 1.3).9 In this particular case, introduction of the desired C3 spacer was undertaken on the. electrophilic component by conjugate addition of the tosylamide with methyl acrylate followed by reduction with LiAlH4 and mesylation. 

Renaud and coworkers have also recently found that related TBDMS-protected B-alkylboronate esters are suitable radical (see Radicals) precursors for conjugate addition to activated olefins such as methyl acrylate (equation 12). Catalyzed hydroborations gave the 1,3-addition products with regioselectivity opposite to those obtained in uncatalyzed reactions. 

Cyclopropanation. The reaction of sulfonium ylides 96 with acrylic esters or methyl vinyl ketone provides rrany-2-arylcyclopropanecarboxylic esters and methyl ketones. Generation of the ylides with EtNP(NMe)2-N=P(NMe)j as base is convenient because dichloromethane can be used as solvent. Another synthesis of cyclopropanecarboxylates proceeds by a conjugate addition and 1,3-elimination sequence. ... 

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