Hydroxyindolizidines

In this case the use of the Doyle dirhodium catalyst Rh2(S-MPPIM)4 (a complex containing the hgand methyl (4S)-2-oxo-3-(3-phenylpropa-noyl)-4-imidazohdine carboxylate) converted the diazoacetate (S)-97 into the ds-flised bicychc lactam (—)-98 in 70% yield together with some dimeric by-products (c. 18%). Elaboration of the piperidine ring entailed lactone cleavage with the anion of phenyl methyl sulfone followed by reduction 

The resulting intermediate (—)-107 underwent cyclization to the piperidine (—)-108 after mesylation and base treatment. Acidic hydrolysis of the acetal and reduction of the resulting cycHc hemiacetal with sodium borohydride produced the triol (—)-109, the vicinal diol component of which was cleaved with periodate before reductive amination with hydrogen and palladium on carbon completed the synthesis of (+)-88. 

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Most of the oxoindolizidines have been prepared by Dieckmann reaction or related condensations. Thus (188) was used to prepare (189), which is a precursor for the synthesis of 2-methyl-1-hydroxyindolizidine (190) (70AP812). Ipalbidine (191a), which is one of the Ipomea group of alkaloids, was prepared as outlined in Scheme 26 (71HCA513). 

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