Michael additions of diethyl malonate

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. 

The Michael addition of nucleophiles to coumarins catalyzed by solid bases provides an interesting approach to the synthesis of 4-substituted 3,4-dihydrocumarins, because with the conventional Michael catalysts the alkaline hydrolysis of the 8-lactone predominates (Scheme 44). Results were obtained when the Michael addition of diethyl malonate to coumarin was catalyzed by the activated Ba(OH)2 292). An unusual 1,2-addition-elimination process at the C = 0 bond was observed. The mechanism of this reaction was explained on the basis of the microcrystalline structure of the catalyst. It was suggested that the rigid coumarin molecule interacts with the Ba ions through the lone-pair electrons of both oxygen atoms of the... 

The Takemoto group synthesized a series ofdiaminocyclohexane-based thiourea derivatives (e.g., 12, 40, 57, and 58) for catalysis of the Michael addition [149-152] ofmalonates to trons-j3-nitrostyrenes (Figure 6.18) [129, 207]. In the model, Michael addition of diethyl malonate to trons-]3-nitrostyrene at room temperature and in toluene as the solvent tertiary amine-functionalized thiourea 12 (10mol% loading) was identified to be the most efficient catalyst in terms of catalytic activity (86%... 

Figure 6.18 Chiral amine 56 and thiourea derivatives (10mol% loading) screened in the asymmetric Michael addition of diethyl malonate to trcms-P-nitrostyrene in toluene.

Scheme 6.61 Mechanistic proposals of the 12-catalyzed asymmetric Michael addition of diethyl malonate to trans-P-nitrostyrene proposed by the Takemoto group (A, B, and C) and initial enolate complex (D) with the ammonium group as additional hydrogen-bond donor initiating an alternative mechanism suggested by Sods, Ptipai, and coworkers.

The synthesis starts with the preparation of diethyl (2-cyanoethyl)malonate (Expt 5.161) by the Michael addition of diethyl malonate to acrylonitrile. Hydrogenation over Raney nickel converts the cyanoethyl compound to the corresponding primary amine (41) which is converted into proline (isolated initially as the hydrochloride) by the reaction sequence shown. Liberation of the free amino acid from its salt is achieved in this case by treatment with triethyl-amine (cf. serine, Expt 5.183). 

Highly substituted tetrahydrothiopyran 1,1-dioxides result from the Michael addition of diethyl malonate to the bis-styryl sulfones 459. On the basis of their NMR spectra, the aryl and aroyl substituents are equatorially disposed (Equation 149) <1999IJB376>. 

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. 

Tsuji has completed three syntheses of zearalenone (119), all by quite similar routes. The first, shown in Scheme 1.28, began with acetate 59b, the minor product from the telomerization of butadiene in acetic acid. Cleavage to the alcohol and gas-phase dehydrogenation led to enone 141. Chain extension to 142 was accomplished in 70% yield by way of Michael addition of diethyl malonate to enone 141. Decarboalkoxylation and protection of the ketone then gave 143 (63%). Conversion of the ester to the primary tosylate 144 was achieved by conventional methods in 62% yield. A Wacker oxidation of the terminal olefin followed by reduction and exchange of the tosylate for an iodide then provided the aliphatic segment 145 in 64% yield. 

Table 3. Michael addition of diethyl malonate (9) to neopentyl glycol diacrylate (8) over CsMCM-41. ...

The activity of cesium over-exchanged MCM-41 has also been tested in the base-catalyzed Michael addition of diethyl malonate (9) to chalcone (12) in a solvent-free system at 423 K [82] (Scheme 8). Conversion of 87 % and selectivity of 91 % to the product 13 were obtained within 30 min. A disadvantage is the poor regenerability of the material, which leads to a drastic decrease in surface area and pore volume. 

CsLa-MCM-41 catalyzes the Michael addition of ethyl cyanoacetate (2) to ethyl acrylate (14) (Scheme 9). Besides formation of the mono adduct (15), bis adduct 16, formed by a double Michael addition, is produced consecutively. Although the basicity of CsLa-MCM-41 is quite mild, its performance in this reaction is very good. Table 4 compares the activity and selectivity obtained with different catalysts. Although product selectivity is probably also controlled by the mesoporous MCM-41 support, the basicity of CsLa-MCM-41 is too weak to catalyze the Michael addition of diethyl malonate under the same conditions. 

Table 2.22 Michael Addition of Diethyl Malonate to Chalcones Under Ball Milling ...

Scheme 17.28 Michael addition of diethyl malonate to chalcone.

The Michael addition of diethyl malonate to ethyl-4-t-butylcyclohexene-l-carboxylate (54) has been comparedwith that of the corresponding nitrile, previously reported. Initial protonation occurs from the equatorial direction and the substituent at C-4 is axial in accord with Zimmerman s theory. Under kinetic control... 

In 1979, Tsuji s group [51] reported an alternative approach to macrolactonization. Inspired by their previous success in the preparation of recifeiolide and 9-decanolide, the authors envisioned that the dimethyl ether of zearalenone (6) could be obtained via olefination using the co-iodoalkyl phenylthioacetate 7 (Scheme 7.2). The Michael addition of diethyl malonate (11) to 10 followed by decarboxylation afforded an ethyl ester, which was reduced to alcohol and converted into the tosylate 12. Wacker-Tsuji oxidation of the terminal olefin was then followed by reduction of the ketone and conversion of the tosylate into iodide to provide 9. This was... 

Methyl dihydrojasmonate is synthesized by the following route (3), namely, Michael addition of diethyl malonate to the pentyl cyclopentenone to obtain the second side chain, followed by hydrolysis and decarboxylation, and finally esterification ... 

More recently, Jang et al. reported a cascade Michael/a-oxyamination reaction of malonates, enals, and a TEMPO-type stable radical by combining iminium catalysis, enamine catalysis, and photoredox catalysis [56], The reaction unified a secondary amine-catalyzed Michael addition of diethyl malonates to enals and a following supported Ru-based photoredox-SOMO catalysis involving a radical trapping event of TEMPO (Scheme 9.61), generating the chiral a, 3-functionalized propanal derivatives with high reactivity and excellent selectivity. 

Table 12.1 Michael addition of diethyl malonate to nitrostyrene promoted by various catalysts [31 a]. ...

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