Meldrum s acid, reaction with

In the case of 3,5-diamino-l,2,4-triazole, the situation was different refluxing in DMF gave two isomers 85 and 86 while application of methanol or iso-propanol as reaction medium allowed obtaining only one reaction product - heterocycles 85 (Scheme 36) [115]. Selective MCR with the formation of corresponding 7-pyrimi-dinenone was also observed when 3-amino-1,2,4-riazoles and Meldrum s acid reacted with ketones instead of aldehydes. 

Stereoselective intramolecular Diels-Alder reactions The reaction of Meldrum s acid (1) with (R)-citronellal (2) in the presence of ethylenediammonium acetate (EDDA)2 at 15-20° results in the tricyclic dihydropyran 3 as the major product with an optical purity of >98%. The product evidently results from an intramolecular hetero-Diels-Alder addition. It can be converted by acid into the optically pure a-methoxycarbonyllactone 4. 

Thus, reaction of thia Meldrum s acid 87 with ethyl vinyl ether 88 with different... 

The three-component reaction of indole (2) with sugar hydroxyaldehyde 281 and Meldrum s acid 282, with a catalytic amount of D,L-proline, afforded the 3-substitution product 283 as a single isomer [203]. The substituent possesses the czs-fused furo [ 3,2- b ] pyranonc skeleton. The proline catalyzes the Knoevenagel condensation of the sugar aldehyde 281 and Meldrum s acid 282 to provide the alkylidene derivative 284 of Meldrum s acid. Then a diastereo-selective Michael addition of indole and an intramolecular cyclization of this adduct 285 with evolution of carbon dioxide and elimination of acetone furnish the furopyranone in one-pot (Scheme 62). 

The reaction of azlactones or a Meldrum s acid derivative with 2-phenylbut-3-ene-2-yl acetate, in the presence of the racemic ligand and a palladium source has provided a new method for controlling alkene geometry. By varying the reaction conditions excellent selectivities for either or Z geometry could be obtained. " ... 

Reaction of Meldrum s acid 584 with the acylimidates 585 gives the enaminones 586 in good yields. Mild heating of 586 causes loss of acetone and carbon dioxide and affords the l,3-oxazin-6-ones 587 in 33-93% yields, Scheme 159 (86CPB1980). 

Amino-5,6-dihydropyrimidin-4(3H)-one 73 was obtained in a multi-component reaction between Meldrum s acid 71, an aldehyde (aliphatic or aromatic) and guanidine carbonate 72 in a small amount of DMF at 120-130 °C. However, 4-methoxyphenyl derivative 73 (R =4-MeOPh) was also obtained in two steps by condensation of arylidene Meldrum s acid 74 with guanidine carbonate (Scheme 29) (06MI10). 

The enantiomerically pure 2,3-unsaturated aldonic lactone 2 was prepared following Sharpless asymmetric dihydroxylation of 2-vinylfuran to give 1 (Scheme 1). The chain-extended aldonolactones 4 and 5 were prepared from the P-keto ester 3 by use of a diastereoselective reduction with either d- or L-tartaric acid in conjuction with sodium borohydride (Scheme 2). Reaction of Meldrum s acid (5a) with D-aldopentoses and hexoses gave 3,6-anhydro-2-deoxy-aldono-... 

The enamine can be formed in situ in a 4CR as well (Scheme 13.36). A primary amine 128 [57] or, in most cases, ammonium acetate [58-61] is reacted with a 1,3-dicarbonyl compound to yield the corresponding enamine. This undergoes nucleophilic addition to the formed Michael acceptor (by reaction of Meldrum s acid 112 with the corresponding aldehydes) followed by cyclization with the Meldrum s acid moiety present in the Michael acceptor molecule. Thus, pyridones are accessible in a 4CR starting from simple, readily available substances. Mostly, acidic conditions are applied for their syntheses, but microwave irradiation under neutral reaction conditions works fine as well. 

In 1978, Yonemitsu et al. published the three-component reaction of Meldrum s acid 112 with various aldehydes 328 and... 

The reaction combines a proline-catalyzed Knoevenagel condensation with the Michael addition of the electron-rich heterocycle (Scheme 13.73). Proline 170 initially condenses with the aldehyde 328 to form an imininm intermediate 331. This is attacked by the CH-acidic Meldrum s acid 112 with subseqnent elimination of proline to provide the Knoevenagel condensation prodnct 332. Nucleophilic 1,4-addition of the indole 327 followed by tautomerizations of the rather unstable intermediate 333 liberates the desired products 330. 

SCHEME 13.89 frans-Cyclopropane spiro componnds 433 from the reaction of Meldrum s acid 112 with aromatic aldehydes 432 and a-thiocyanato ketones 431. 

Dihydropyranones The use of Meldrum s acid as a CHj-C(0) equivalent was successfully applied in the synthesis of 3,4-dihydropyranones. The reaction of Meldrum s acid 112 with several aldehydes 453 and dim-edone 15 under grinding conditions to form 3,4-dihydropyranones 454 was reported by Rong in 2007 (Scheme 13.95) [186]. 

Meldrum s acid derivatives are used as ketene precursors, but reaction of carbamoyl-substituted Meldrum s acid 174 with trimethylsilyl chloride and a secondary amine forming product amides was shown to proceed with... 

The synthesis of trans-3-acyl- 3-lactam methyl esters 107 has been reported by Almqvist and coworkers [81, 82] by the Staudinger reaction of ketenes, generated from the Meldrum s acids 105, with methyl (i )-thiazoline-4-carboxylate 106 in benzene in the presence of hydrogen chloride (Scheme 3.36). An exceptionally low yield of 38% was obtained in the reaction of acetylketene. These esters could then be selectively reduced to the corresponding aldehydes 108 in moderate yields using diisobutylaluminum hydride (DIBAL-H). The Meldrum acids are well-known precursors of ketenes [83, 84]. They undergo a pericyclic reaction under thermal influence to generate ketenes with the release of carbon monoxide and acetone. 

Pyrolysis of Meldrum s acid derivatives with a suitably placed hydroxyl group can lead to the formation of ring-fused pyranones, as illustrated by the reactions of 356 (2010S1361) and 358 (20100BC4383) to give the indole- and pyrrohzinone-fused products 357 and 359, respectively (Scheme 70). 

Since allylation with allylic carbonates proceeds under mild neutral conditions, neutral allylation has a wide application to alkylation of labile compounds which are sensitive to acids or bases. As a typical example, successful C-allylation of the rather sensitive molecule of ascorbic acid (225) to give 226 is possible only with allyl carbonate[l 37]. Similarly, Meldrum s acid is allylated smoothly[138]. Pd-catalyzed reaction of carbon nucleophiles with isopropyl 2-methylene-3,5-dioxahexylcarbomite (227)[I39] followed by hydrolysis is a good method for acetonylation of carbon nucleophiles. 

One route to o-nitrobenzyl ketones is by acylation of carbon nucleophiles by o-nitrophenylacetyl chloride. This reaction has been applied to such nucleophiles as diethyl malonatc[l], methyl acetoacetate[2], Meldrum s acid[3] and enamines[4]. The procedure given below for ethyl indole-2-acetate is a good example of this methodology. Acylation of u-nitrobenzyl anions, as illustrated by the reaction with diethyl oxalate in the classic Reissert procedure for preparing indolc-2-carboxylate esters[5], is another route to o-nitrobenzyl ketones. The o-nitrophenyl enamines generated in the first step of the Leimgruber-Batcho synthesis (see Section 2.1) are also potential substrates for C-acylation[6,7], Deformylation and reduction leads to 2-sub-stituted indoles. 

Thionyl chloride (11.5g, 96.4 mmol) was added to 2-nitrophenylacetic acid (8.72g, 48.2mmol) and the suspension was warmed to 50°C and stirred until gas evolution was complete. The resulting solution was concentrated in vacuo and the residue dissolved in CHjClj (30 ml). This solution was added dropwise to a stirred solution of Meldrum s acid (6.94 g, 48.2 mmol) in CH2CI2 (200 ml) under nitrogen at 0 C. The solution was stirred at 0" C for 1 h after the addition was complete and then kept at room temperature for an additional hour. The reaction solution was then worked up by successively washing with dil. HC1, water and brine and dried (MgSOJ. The dried solution was concentrated in vacuo and abs. ethanol (200 ml) was added to the residue. The mixture was... 

To set the stage for the crucial carbene insertion reaction, the acetic acid side chain in 32 must be homologated. To this end, treatment of 32 with 1,l -carbonyldiimidazole furnishes imidazo-lide 33, a competent acylating agent, which subsequently reacts with the conjugate base of Meldrum s acid (34) to give 35. Solvolysis of this substance with para-nitrobenzyl alcohol in acetonitrile at reflux provides /Mceto ester 36 after loss of one molecule of ace-... 

The addition of terminal alkynes to carbon-carbon double bonds has not been explored until recently, possibly because C=C double bonds are not as good electrophiles as C=N or C=0. In 2003, Carreira et al. reported the first conjugate addition reaction of terminal alkynes to C=C catalyzed by copper in water. The reaction proceeded with derivatives of Meldrum s acid in water in the presence of Cu(OAc)2 and sodium ascorbate (Eq. 4.35).59 However, this method was limited to C=C double bonds with two electron withdrawing groups. 

Reaction of the enatiopure aldehyde 2-800, obtained from the corresponding imine by enantioselective hydrogenation, with Meldrum s acid (2-801) and the enol ether 2-802a (E/Z= 1 1) in the presence of a catalytic amount of ethylene diammonium diacetate for 4h gave 2-805 in 90 % yield with a 1,3 induction of >24 1. As intermediates, the Knoevenagel product 2-803 and the primarily produced cycloadduct 2-804 can be supposed the latter loses C02 and acetone by reaction with water formed during the condensation step (Scheme 2.178). 

The reactions of Meldrum s acid (421) and acyl isothiocyanates in DMSO in the presence of lithium hydride at ambient temperature for 2-3 hr gave the lithium salts (457), which were alkylated by treatment with alkyl halide for 5 hr to afford isopropylidene (acylamino)(alkylthio)methy-lenemalonates (458) in 20-90% yields (87ZC68). 

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