Malononitriles Michael reactions

Scheme 6.68 Typical adducts obtained from the 12-catalyzed asymmetric Michael reaction between malononitrile and a.P-unsaturated N-acyl pyrrolidinones (cyclic imides) the values in parentheses refer to reactions at lower concentration (0.1 M).

The addition of nitromethane (56% yield/168h 87% ee) or methyl a-cyanoacetate (94% yield/52h 82% ee) as alternative CH-acidic methylene compounds required increased reaction temperatures (60 to 80 °C) to furnish the adducts 7 and 8. As exemplarily depicted in Scheme 6.69 for benzylic alcohol thiourea 12 catalyzes the transformation of the obtained malononitrile Michael products to the respective carboxyhc acid derivatives (89% yield/88h). This method of derivatization also described for methanol (87% yield/24h rt), benzyl amine (77% yield/3h rt), and N,0-dimethylhydroxyamine (75% yield/20h 60°C) as nucleophiles was reported to be feasible as a one-pot strategy without isolation of the initially formed Michael adduct [222]. 

Ni(II)(OAc)2bpy and Co(II)(OAc)2bpy catalyze the Michael addition of nitro-methane, malononitrile, and aniline to a,j8-unsaturated ketones, methyl acrylate, and acrylonitrile in DMF under neutral conditions [116]. FeCls 6H2O is a highly efficient catalyst of Michael reaction of 1,3-dicarbonyl compounds with a,/3-unsaturated ketones under mild and neutral conditions (Sch. 24) [117]. There is literature precedent for this reaction with dual catalysis Ni(II) immobilized on a clay support and FeCl3 to activate the enone [118]. The mechanism proposed for the single-center catalysis involves coordination of the enone to a diketonato complex [119]. The chemo-... 

As base. Many reactions that are promoted by a base can be effected with KF/AljO, for example, in deprotonating malononitrile for Michael reaction, in N-pyridylation of indole which is based on the S,.jAr mechanism, and in the preparation of a-heterosubstituted Weinreb amides from 7V-methoxy-A(-methyl chloroacetamide. ... 

The COj species in the HT interlayer could be exchanged with OH ions by calcination at 723 K and hydration at room temperature. A spinel phase of Mg-Al mixed oxide obtained after the calcination transforms into the original layered structure during the hydration. This reconstruction is known as the memory effect of HT materials. The reconstructed HT catalyzed the Knoevenagel condensation of various aldehydes with nitriles in the presence of water [119]. The reconstracted HT also showed an aqueous Michael reaction of nitriles with a,p-unsaturated compounds. The layered double-hydroxide-supported diisopropylamine catalyzed the Knoevenagel condensation of aromatic carbonyl compounds with malononitrile or ethyl cyanoacetate [120]. This solid base could be recycled at least four times, and exhibited activity for aldol, Henry, Michael, transesterification, and epoxidation of alkenes. 

Scheme 19.19 Michael reaction of benzimides with malononitrile catalysed by thiourea 15.

In 2012, a chiral cinchona alkaloid-derived primary amine was associated by Wang et al. to a (R)-BINOL-derived phosphoric acid to induce a three-component domino Knoevenagel-Michael reaction between isatins, malononitrile, and acetone, providing the corresponding domino products in generally excellent yields and enantioselectivities, as shown in Scheme 2.13. A hypothetic cooperative catalysis can be envisaged to explain these excellent results. 

As shown above, it was not so easy to optimize the Michael addition reactions of l-crotonoyl-3,5-dimethylpyrazole in the presence of the l ,J -DBFOX/ Ph-Ni(C104)2 3H20 catalyst because a simple tendency of influence to enantio-selectivity is lacking. Therefore, we changed the acceptor to 3-crotonoyl-2-oxazolidi-none in the reactions of malononitrile in dichloromethane in the presence of the nickel(II) aqua complex (10 mol%) (Scheme 7.49). For the Michael additions using the oxazolidinone acceptor, dichloromethane was better solvent than THF and the enantioselectivities were rather independent upon the reaction temperatures and Lewis base catalysts. Chemical yields were also satisfactory. 

Finally we have performed the Michael addition reactions of malononitrile and 3-(2-alkenoyl)-2-oxazolidinones in dichloromethane in the presence of the R,R-DBF0X/Ph-Ni(C104)2-31 20 and TMP (10 mol% each). Enantioselectivities were a little lower than 90% ee for acceptors having a variety of / -substituents. The best selectivity was 94% ee in the reaction of t-butyl-substituted acceptor (Scheme 7.50). 

Reactions of a,(3-unsaturated acylzirconocene chlorides with stable carbon nucleophiles (sodium salts of dimethyl malonate and malononitrile) at 0°C in THF afford the Michael addition products in good yields (Scheme 5.38). Direct treatment of the reaction mixture with allyl bromide in the presence of a catalytic amount of Cul -2LiCl (10 mol%) in THF at 0 °C gives the allylic ketone in a one-pot reaction. This sequential transformation implies the electronic nature of a,P-unsaturated acylzirconocene chloride to be of type E as shown in Scheme 5.37. 

Knoevenagel adduct 239 of oxohomophthalimide 240 with malononitrile 27a in reactions with CH-acids behaves ambiguously (82CPB1215). Reactions of 239 with acetylacetone, ethyl esters of acetoacetic and ben-zoylacetic acids, as well as methyl pyruvate led to the formation of the desired spiropyrans 241. However, benzoylacetone, dibenzoylmethane, cyanacetamide, and oxindole always gave the same 242. Authors explain this feature in terms of a retro-cleavage of adducts of Michael product 239... 

Highly substituted [l,6]naphthyridines have been prepared by the Michael addition and subsequent Thorpe-Ziegler cyclization of a series of chalcones with malononitrile in the presence of pyrrolidine, over extended periods of heating <1999SC3881>. Attempts to reduce the reaction times using microwave irradiation gave mixtures of products... 

The cyclization of 5-oxonitriles offers an attractive route to 2-amino-4//-pyrans (Scheme 18) (78JHC57). The starting materials, a-benzoylcinnamonitriles, are available from benzoyl-acetonitrile and an aromatic aldehyde. Michael addition of ethyl cyanoacetate or malononitrile to the benzoylcinnamonitrile affords the oxonitrile and is followed by cyclization to the imine. The reaction proceeds at room temperature in the presence of either piperidine or sodium ethoxide. 

Various unsaturated compounds, such as CO2, isocyanates and aldehydes, undergo Pd-catalysed cycloaddition with vinyl epoxides. Reaction of CO2 with 127 affords cyclic carbonates 128 with retention of the configuration at C(3), offering a method of cis hydroxylation of epoxides [66], and has been used for the synthesis of the side-chain unsaturated (—)-exo-brevicomin (129) [67], The tetrahydrofuran 131 was prepared by [3+2] cycloaddition of activated alkenes such as benzylidene malononitrile (130) with vinyl epoxide via Michael addition and allylation [68],... 

In a one-pot three-component reaction, aromatic aldehydes, malononitrile and 1,3-dicarbonyl compounds react to form 2-amino-5-carboxy-4-aryl-47/-pyran-3-carbonitriles 87. The reaction proceeds by an initial Knoevenagel condensation of malononitrile with the aromatic aldehyde to afford the 2-benzylidenemalononitrile intermediate 88. Michael addition of the activated methylene group forms the 1,5-dicarbonyl equivalent 89, which upon ring closure affords 477-pyrans (Scheme 29) <2004SL871, 1999H(51)1101 >. 

Michael addition of the anion from malononitrile to the conjugated system (246) results in the pyranopyrazole (247) (74AP444). For (246 R = Ph) adducts form with vinyl ethers at 70-80 °C. With extra activation (246 R = PhCO or MeCO) the adducts form at room temperature. The reaction is regiospecific but gives a mixture of cis (248 ca. 80%) and trans (249 ca. 20%) isomers (Scheme 77) (80JPR711). 

The first step of this process involves the Knoevenagel condensation of an aldehyde with malononitrile to form the corresponding Knoevenagel product (5). The second molecule of malononitrile then undergoes Michael addition to 5 followed by simultaneous thiolate addition to C N of the adduct and cyclization to dihydropyridine (6) which on aromatization and oxidation (air) under the reaction conditions leads to pyridine. 

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