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

Abstract

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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“…Alkylation of cyclic 1,3-diones (Method A ) is notoriously difficult, but we were able to achieve modest yields in cases where the alkylating agent was either allylic or benzylic (VATs 1 , 3 , and 5 ) . In general, however, it was more convenient (and effective in terms of overall yield) to condense the appropriate aldehyde with excess 1,3-cyclohexanedione using proline catalysis, followed by conjugate reduction of the intermediate 2-alkylidene-dione (Method B , Scheme ). , …”

An updated review of fatty acid residue-tethered heterocyclic compounds: synthetic strategies and biological significance

“…Then the deviation started, the pseudo pyronine 194 was achieved by reducing 193a. 82 Alternatively, the achievement of pseudopyrone B 197 began with the deacylation of 193b to yield 6-heptyl-4-hydroxy-2-pyrone 195 followed by acylation to furnish 196, which was reduced giving 197 (ref. 83 ) ( Scheme 40 ).…”

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