Cyclopentanes carbon nucleophile cyclization

This Pd-catalyzed cascade bis-cyclization reaction can also be applied to trans linear substrates 40 and 41. It was possible to effect either 5-exo or 6-endo cyclizalion selectively by an appropriate choice of the electron-withdrawing substituents of the nucleophile, as illustrated in Scheme 20. Ero-cyclizations were observed when sterically encumbered nucleophiles were employed. Cyclopentanes were obtained as a result of steric interactions between the nucleophile and one of the allylic hydrogens of the linear substrate. Endo-cyclizations leading to trani-octahydrophenanthrene were the only reactions observed when less sterically demanding nucleophiles were employed. Notably, these cyclizations proceed in a completely stereoselective trans manner. Attack of the carbon nucleophile onto a double bond electrophilicaUy activated by the palladium species results in a trans configuration of the fused ring junction. This stereochemistry is defined by that of the double bond in the initial substrate the relative configuration of compound 42 or 43 is hereby controlled. 

The following acid-catalyzed cyclizations leading to steroid hormone precursors exemplify some important facts an acetylenic bond is less nucleophilic than an olelinic bond acetylenic bonds tend to form cyclopentane rather than cyclohexane derivatives, if there is a choice in proton-catalyzed olefin cyclizations the thermodynamically most stable Irons connection of cyclohexane rings is obtained selectively electroneutral nucleophilic agents such as ethylene carbonate can be used to terminate the cationic cyclization process forming stable enol derivatives which can be hydrolyzed to carbonyl compounds without this nucleophile and with trifluoroacetic acid the corresponding enol ester may be obtained (M.B. Gravestock, 1978, A,B P.E. Peterson, 1969). 

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