Dieckmann condensation stereochemistry

In our last look at prostaglandins, we can see this put to use in an approach to some prostaglandin derivatives. The plan was to construct PG derivatives from an intermediate of type 216. This j8-ketoester was to be derived from a Dieckmann condensation (construction of the C9-C10 bond). The Dieckmann precursor was to be derived from the reaction of malonate 215 with geminally activated cyclopropane 214. Note that control of absolute stereochemistry in this route leads back to 209, which was resolved as its brucine salt. It is also notable that 214 reacts selectively with malonate 215 at the more hindered secondary (but allylic) carbon of the cyclopropane with clean inversion of configuration. 

A partial synthesis of villalstonine (322) has been achieved by Cook, following the biomimetic method of LeQuesne (223), by condensation of synthetic (-i-)-macroline (338), or the more stable macroline equivalent (341), with natural pleiocarpamine (342) in ().2N HCl, to furnish villalstonine (Scheme 22). The (+)-macroline was prepared starting from the optically active tetracyclic ketone 343, prepared from D-(-i-)-tryptophan by an en-antiospecific Pictet Spengler reaction and stereocontrolled Dieckmann cyclization. The synthesis (Scheme 23) features the use of a stereoselective Claisen rearrangement, followed by stereospecific hydroboration-oxidation of the exocyclic methylene function at C(16), to install the required C(15) and C(16) stereochemistry (225-227). 

In addition to executing the syntheses of yohimbine (4) and j8-yohimbine (5), Szantay has also developed methods to elaborate the ketone 260 to alloyohimbine (7) and a-yohimbine (8) by utilization of the Dieckmann strategy (Scheme 3.44) (50). Ketone 260 was condensed with methyl cyanoacetate to afford the a,j8-unsaturated ester 272. Reduction with NaBH4 followed by saponification provided diacid 273 which has the cis-stereochemistry required for the DE-ring fusion in the yohimbine targets. Subsequent decarboxylation of 273 followed by hydrolysis and esterification afforded diester 274 which underwent the key Dieckmann cyclization in modest yield to... 

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