Malonates reaction with chalcone

There is an example of alkaloid-induced asymmetric reactions in an IL medium. Dimethyl malonate reacted with chalcone under the action of potassium carbonate in the presence of quininium-derived phase transfer catalyst (PTC) 27 in a [bmim] [PFg] melt to give adduct 28 in high yield but with a slightly lower enantioselectivity than in conventional organic solvents (DMSO or toluene) (Scheme 22.10) [49]. Most surprisingly, the absolute configuration of product 28 reversed in the IL medium. Additional experiments with quinine or N-(4-nitrobenzyl)quininium bromide as PTC indicated that the reversal of enantioselectivity was not due to the PTC but can be attributed to the cation associated with the anion of the ionic liquid. The process was successfully repeated in the presence of the recovered IL/PTC system without a reduction in reaction rate or product yield. 

The activated Ba(OH)2 catalyst was successfully used for the Michael reactions of chalcone with active methylene compounds 290), as well as for the Michael reaction of other benzylidene derivatives of acetone, butanone, 3-methylbutanone, 4-methyl-2-pentanone, and 3,3-dimethylbutanone with ethyl acetoacetate and diethyl malonate. The reaction with diethyl malonate gave good yields of the Michael adduct (between 65 and 93%), whereas with ethyl acetoacetate various products were obtained, depending on temperature and amount of catalyst (Scheme 43) 291). Thus, by varying the reaction conditions, it was possible to obtain a single product with practically 100% selectivity, the yields being higher than those obtained with soluble catalysts, such as KOH, NaOH, or piperidine. 

Recently, Maruoka and coworkers addressed the importance of dual-functioning chiral phase-transfer catalysts such as 70a for obtaining a high level of enantio-selectivity in the Michael addition of malonates to chalcone derivatives (Scheme 5.35) [37]. For instance, the reaction of diethyl malonate with chalcone in... 

Most of the publications on the reactions of malonic acid derivatives are devoted to the reaction of a,(3-unsaturated carbonyls with malononitrile 107. In this book we do not describe the results of all known publications but only the most characteristic or interesting ones in our opinion. The reactions of unsaturated ketones with malononitrile are usually carried out in methanol or ethanol in the presence of ammonium acetate [102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117]. Treatment of malononitrile 107 with chalcone 5 [115] and its heterocyclic analogue 109 [104] yielded 3-cyanopyri-dines 108 and 110 (Scheme 3.33). 

Rann et al. reported the dramatic influence of a new tailor-made, task-specific, and stable ionic liquid, butyl methyl imidazolium hydroxide ([bmim][OH]), in Michael addition. They have discovered that a task-specific ionic liqnid [bmim][OH] efficiently promoted the Michael addition of 1,3-dicarbonyl compounds, cyano esters, and nitro alkanes to a variety of conjugated ketones, carboxylic esters, and nitriles withont reqniring any other catalyst and solvent (Fig. 12.21) [16]. Very interestingly, all open-chain 1,3-dicarbonyl componnds such as acetylacetone, ethyl ace-toacetate, diethyl malonate, and ethyl cyanoacetate reacted with methyl vinyl ketone and chalcone to give the usual monoaddition products, whereas the same reactions with methyl acrylate or acrylonitrile provided exclusively bis-addition products. 

This approach has also been applied to the use of malonates as C-H acidic carbon pro-nucleophiles, observing that the reaction performed excellently with a wide range of different chalcones and (3-aryl substituted 2-butenones (Scheme 4.28). Moreover, other 1,3-dicarbonyl compounds and related derivatives such as malononitriles, (3-ketoesters, 2,4-pentanedione and ethyl nitroacetate have also been tested with success in the reaction using chalcone as Michael acceptor. In an independent work, the use of cyanoacetates was also surveyed with good results, although in this case mixtures of diastereoisomers were typically obtained. In all these cases, the stereochemical outcome of the reaction was consistent with the model proposed by Soos. 

Reaction Between Chalcone and Cyclic Enones with Malonates... 

The strong basic sites associated with surface OH groups are responsible for the catalytic activity of the activated Ba(OH)2 in organic reactions, such as the Michael addition (285). The authors showed, for example, that the Michael addition of diethyl malonate to chalcone catalyzed by activated Ba(OH)2 yielded 95% of the Michael adduct. When Ba(OH)2 was selectively poisoned with TBMPHE, a conversion of only 5% was observed, however when Ba(OH)2 was poisoned with DNB a conversion of 58% was obtained. The small poisoning effect of DNB indicates that only a small number of reducing sites with basic character (e.g., 0 ) can act in the process as basic sites. Thus, it was concluded that the basic sites responsible for the catalytic activity must be surface OH groups on the Ba(OH)2 H2O. 

Shibasaki made several improvements in the asymmetric Michael addition reaction using the previously developed BINOL-based (R)-ALB, (R)-6, and (R)-LPB, (R)-7 [1]. The former is prepared from (R)-BINOL, diisobutylaluminum hydride, and butyllithium, while the latter is from (R)-BINOL, La(Oz -Pr)3, and potassium f-butoxide. Only 0.1 mol % of (R)-6 and 0.09 mol % of potassium f-butoxide were needed to catalyze the addition of dimethyl malonate to 2-cy-clohexenone on a kilogram scale in >99% ee, when 4-A molecular sieves were added [15,16]. (R)-6 in the presence of sodium f-butoxide catalyzes the asymmetric 1,4-addition of the Horner-Wadsworth-Emmons reagent [17]. (R)-7 catalyzes the addition of nitromethane to chalcone [18]. Feringa prepared another aluminum complex from BINOL and lithium aluminum hydride and used this in the addition of nitroacetate to methyl vinyl ketone [19]. Later, Shibasaki developed a linked lanthanum reagent (R,R)-8 for the same asymmetric addition, in which two BINOLs were connected at the 3-positions with a 2-oxapropylene... 

Complex LSB 9 is readily prepared either by the reaction of La(0 Pr)3 with 3 equiv. of B1NOL followed by the addition of NaO Bu (3 equiv.) or by the reaction of LaCl nfLO with sodium binaphthoxide. The complex 9 is stable to oxygen and moisture and has been proven to be effective in the catalytic Michael reaction of various enones with either malonates or p-keto esters. The Michael adducts with up to 92% ee were obtained in almost quantitative yield. Typical results with malonates are summarized in Table 8D.1 (Ln = lanthanide) [18], In general, the use of THF as solvent gave the best results except for the case of the LSB-catalyzed reaction of rmns-chalcone with dimethyl malonate, wherein the use of toluene was essential to give the adduct with good enantiomeric excess. The effects of the central metal (La, Pr, and Gd) on asymmetric induction were also examined in the same reaction, and LSB was found to be the best catalyst. 

Chalcone 1 and malonate 2 in stoichiometric amounts (5 mmol) were vigorously shaken with a mechanical stirrer during 1 h at the required temperature (generally 60 °C) in the presence of catalytic quantities (6% mol) of KOH and chiral ammonium salt 4. Then, the reaction mixture was cooled to room temperature and extracted with methylene chloride (50 mL). Product 3 was purified by chromatography on silica gel. Yield 57%, 68% ee. 

Another possible probe could be the Michael addition of diethyl malonate to chalcone (Scheme 7) [192], This dosimeter operates in a toluene solution of chalcone and diethyl malonate with suspended powdered potassium hydroxide. Under sonication and in the presence of a phase transfer agent this reaction is too fast, but its rate can be conveniently controlled by adjusting the reagent concentrations in the absence of the phase transfer agent. Interestingly, the size of the KOH particles is not an important parameter since this solid is rapidly disrupted down to an average size of ca. 60 pm. 

Kumamoto, T., Rhine, K., Endo, M. et al. (2005) Guanidine-catalysed asymmetric addition reactions Michael reaction of cyclopentenone with dibenzyl malonates and epoxidation of chalcone. Heterocycles, 66, 347-359. 

Ultrasound Esterifications, etherification and hydrolysis of esters Michael addition involving the addition of chalcone to diethyl malonate in SLPTC mode Synthesis of benzyl sulfide by reaction of solid sodium sulfide with benzyl chloride Synthesis of fiuvenese from phenylacetylene Davidson et al. (1987) Raioarinoro et al. (1992) Contamine el al. (1994) Hagenson et al. (1994) Wang and Zhao (1996)... 

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