Cyclopentane-1,2,4-trione synthesis

The reaction of diethyl oxalate with ketones in the presence of sodium ethoxide, or other bases, has been used extensively examples are given in Scheme 66. Reaction may occur with esterketone ratios of 1 1, 2 1, or 1 2, but only the 1 1 case finds substantial use in modem synthetic practice. Frequently the a-oxalyl ketone is thermally decarbonylated to give the 3-heto ester.An early example of this was provided by Bachmann s synthesis of equilenin. The mechanism of this reaction has teen examined labeling studies showed that it was the ester carbonyl that was eliminated. The intact oxalyl group has teen used as a directing group in steroid methylation while, more recently, 2-oxalylcyclohexanone has provided a route to (R)-(-)-hexahydromandelic acid (Scheme 67). The products of acylation of suitable acyclic ketones can cyclize to form (enolic) cyclopentane-1,2,4-triones (equation 39). ... 

The first result in this field was the reduction of 2-(6-carbomethoxy-hexyl)cyclopentane-l,3,4-trione with [Rh(COD)(ACMP)2]" BF4 as catalyst to 2-(6-carbomethoxy-hexyl)-4-(R)-hydroxycyclopentane-l,3-dione, an intermediate of the Ei prostaglandine synthesis (12) ... 

The synthesis began with cyclopentan-l,3-dione 75. A Robinson annela-tion gave 77 via intermediate trione 76. Reduction of the more electrophilic of the two ketones gave 78, which was protected as tetrahydropyranyl ether 79. Deconjugative alkylation of 79 gave 80. Hydrolysis of the THP protecting group and reduction of the ketone (pseudo-axial delivery of hydride) provided 81/82. 

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