Reduction of isopropylidene acylmalonates, 5-acylbarbituric acids, and 3-acyl-4-hydroxycoumarins to the corresponding alkyl derivatives by sodium cyanoborohydride-acetic acid

Nutaitis, Charles F.; Schultz, Rose Ann; Obaza, Judy; Smith, F.

doi:10.1021/jo01311a011

Cited by 37 publications

(15 citation statements)

References 2 publications

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“…In situ treatment of aldehyde 7 with an amine and sequential hydrogenation of the formed imine with H 2 in the presence of Pd/C or with NaBH(OAc) 3 gives γ-substituted amines 8. 8 (D) 5-Alkyl Meldrum's acids 1 are used for the rapid synthesis of 2-alkyl acrylates 9 via Mannich-type reactions.…”

Section: Scheme 1 Abstractsmentioning

confidence: 99%

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5-Alkyl and 5,5-Dialkyl Meldrum’s Acids

Mieriņa

2013

Synlett

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This feature focuses on a reagent chosen by a postgraduate, highlighting the uses and preparation of the reagent in current research spotlight Introduction 5-Alkyl and 5,5-dialkyl Meldrum's acids (1 and 2, respectively) are used in total synthesis. 1 Monoalkylated derivatives 1 are synthesized from Meldrum's acid 3 by condensation with aldehyde 2 (or by acylation 3 ) followed by hydrogenation. 5-Alkyl and 5,5-Dialkyl Meldrum's Acids5,5-Dialkyl Meldrum's acids 2 can be obtained by alkylation of Meldrum's acid 3 or its monoalkylated derivatives 1 (Scheme 1). 4 Herein, reactions of Meldrum's acids 1 and 2 proceeding with destruction of 1,3-dioxane cycle are reviewed.(A) Hydrolysis of Meldrum's acid 2 leads to malonic or acetic acid derivatives. 5 Radical reduction of compound 2 with SmI 2 and H 2 O forms 3-hydroxypropanoic acids 4 selectively. The first step is activation of Meldrum's acid via coordination of SmI 2 to the carbonyl group, followed by electron transfer. 6 (B) Detz et al. 7 have reported that dimethyl malonate 5 can be obtained from propargylic derivative 2. The authors propose that the first step of the reaction cascade is copper-mediated addition of Meldrum's acid 2 to the triple bond and sequential methanolysis of the dioxane cycle forming lactone 6, which is further cleaved with methoxide leading to compound 5.(C) β-Substituted aldehydes 7 can be synthesized by Lewis base promoted hydrosilylation of Meldrum's acids 1 with phenylsilane, followed by hydrolysis. In situ treatment of aldehyde 7 with an amine and sequential hydrogenation of the formed imine with H 2 in the presence of Pd/C or with NaBH(OAc) 3 gives γ-substituted amines 8. 8 (D) 5-Alkyl Meldrum's acids 1 are used for the rapid synthesis of 2-alkyl acrylates 9 via Mannich-type reactions. The advantage of the method is the clean conversion into products due to the formation of volatile by-products -acetone, carbon dioxide, and dimethylamine. 9

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Section: Scheme 1 Abstractsmentioning

confidence: 99%

“…1 Monoalkylated derivatives 1 are synthesized from Meldrum's acid 3 by condensation with aldehyde 2 (or by acylation 3 ) followed by hydrogenation.…”

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5-Alkyl and 5,5-Dialkyl Meldrum’s Acids

Mieriņa

2013

Synlett

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“…Indeed, our attempted reactions of 1 and 1,3-diethyl-2-thiobarbituric acid (2) with either butyric chloride or butyric anhydride under the conditions indicated above produced only traces of the substituted product. On the other hand, compound 1 is efficiently acylated by reaction with an alkanoyl chloride when conducted in pyridine [9]. It appears that pyridine undergoes a reaction with the acid chloride to generate an intermediate N-acylpyridinium cation that is more reactive than the starting acid chloride [9,10].…”

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“…On the other hand, compound 1 is efficiently acylated by reaction with an alkanoyl chloride when conducted in pyridine [9]. It appears that pyridine undergoes a reaction with the acid chloride to generate an intermediate N-acylpyridinium cation that is more reactive than the starting acid chloride [9,10]. Unfortunately, this method is not suitable for the preparation of nucleophilesensitive compounds such as 3-6 (Scheme 1).…”

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Synthesis of 5‐(functionalized acyl)‐1,3‐dialkyl‐substituted barbituric and 2‐thiobarbituric acids

Zoorob

Ismail

Strękowski

2001

Journal of Heterocyclic Chem

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A sodium derivative of 1,3-dimethylbarbituric acid or 1,3-diethyl-2-thiobarbituric acid undergoes an efficient monoacylation at C5 by the reaction with ω-chloroalkanoyl chloride or diacid dichloride in the presence of pyridine in tetrahydrofuran. A nucleophilic displacement of the chlorine in a 5-chloroacetylbartiburate can be accomplished by using a one-pot procedure. By contrast, a similar transformation of a 5-(chlorobutanoyl)barbituric acid requires intramolecular cyclization in the presence of a nonnucleophilic base followed by treatment with a nucleophile of the resultant 5-[4,5-dihydro(3H)-2-furylidene]barbiturate.

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“…It should be noted that NaBH 3 CN has received extensive application in organic reductions as versatile and remarkably selective reagent. 5 Two decades ago Nutaitis et al 6 have demonstrated that treatment of acyl derivatives of Meldrum ' s acid, 5-acylbarbituric acids as well as dehydroacetic acid and 3-acyl-4-hydroxycoumarins with 2 equivalents of NaBH 3 CN in AcOH led to hydrogenolysis of the carbonyl group of the acyl substituent to give the corresponding alkyl derivatives in excellent yields. Kende et al successfully applied this protocol for selective reduction of some acyl coumarines and acyl pyrimidine triones.…”

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An Efficient Synthesis of Alkyl Substituted Cyclic 1,3-Diones

Pashkovsky¹,

Lokot²,

Лахвич³

2001

Synlett

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An efficient method for the synthesis of cyclic a-alkyl b-dicarbonyl compounds of cyclopentane, cyclohexane, tetronic acid and a-pyrone series is described. The method consists of the selective transformation of the corresponding cyclic b,b'-tricarbonyl compounds by NaBH 3 CN in a mixture of THF and 2N aqueous HCl.2-Alkyl cycloalkane-1,3-diones as well as 3-alkyltetronic acids, and 3-alkyl-3,4-dihydro-2H-pyran-2,4-diones have found a widespread application in the synthesis of natural and structurally related compounds. 1 Earlier we have developed a method for obtaining 2-alkyl cycloalkane-1,3-diones and their heterocyclic analogs starting from the readily available 2-acylcyclohexane-1,3-diones, 2-acylcyclopentane-1,3-diones, 3-acyltetronic acids, and 3-acyl-3,4-dihydro-2H-pyran-2,4-diones. 2 The method consists of the regioselective hydrogenolysis of the carbonyl function at the side chain of the latter compounds under the action of Et 3 SiH in CF 3 CO 2 H in the presence of catalytic amounts of BF 3 ×OEt 2 or LiClO 4 (ionic hydrogenation). 3 The yields of the target b-dicarbonyl compounds were in the range of 66-98%. In the case of arylidene acyl derivatives of cyclic b-dicarbonyl compounds saturation of conjugated double bond of arylidene acyl fragment occurs along with hydrogenolysis of the carbonyl function. Additionally, in furylidene acyl derivatives reduction of the furan ring takes place.In the course of our investigations directed towards the synthesis of natural products we searched for alternative methods for selective reduction of cyclic b,b'-triones. In view of the similar mechanistic aspects of the carbonyl function reductions by NaBH 3 CN in acidic medium 4 to those of reductions by organosilanes, we focused our attention on the use of NaBH 3 CN for our synthetic purpose. It should be noted that NaBH 3 CN has received extensive application in organic reductions as versatile and remarkably selective reagent. 5 Two decades ago Nutaitis et al. 6 have demonstrated that treatment of acyl derivatives of Meldrum ' s acid, 5-acylbarbituric acids as well as dehydroacetic acid and 3-acyl-4-hydroxycoumarins with 2 equivalents of NaBH 3 CN in AcOH led to hydrogenolysis of the carbonyl group of the acyl substituent to give the corresponding alkyl derivatives in excellent yields. Kende et al. successfully applied this protocol for selective reduction of some acyl coumarines and acyl pyrimidine triones. 7 Therefore, it was of interest to extend the scope of the method by Nutaitis et al. to b,b'-tricarbonyl compounds of the cyclohexane, cyclopentane and tetronic acid series. However, in our hands attempted application of this protocol to some b,b'-triones 1 showed that although the reduction proceeded regioselectively at the side chain the yields of the corresponding a-alkyl-b-dicarbonyl compounds 2 in general were remarkably lower as compared with the method of ionic hydrogenation. Probably, this is due to incomplete crystallization of the reaction products from dilute aqueous solutions of AcOH during work-up of ...

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Reduction of isopropylidene acylmalonates, 5-acylbarbituric acids, and 3-acyl-4-hydroxycoumarins to the corresponding alkyl derivatives by sodium cyanoborohydride-acetic acid

Cited by 37 publications

References 2 publications

5-Alkyl and 5,5-Dialkyl Meldrum’s Acids

5-Alkyl and 5,5-Dialkyl Meldrum’s Acids

Synthesis of 5‐(functionalized acyl)‐1,3‐dialkyl‐substituted barbituric and 2‐thiobarbituric acids

An Efficient Synthesis of Alkyl Substituted Cyclic 1,3-Diones

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