The stereocontrolled synthesis of naturally occurring products containing a 5,5-spiroketal molecular structure represents a major synthetic problem. Moreover, in a previous work, the stereocontrolled synthesis of cephalosporolide E (ceph E), which presumably was obtained from its epimer congener (ceph F) through an acid-mediated equilibration process, was reported. Consequently, we performed a theoretical investigation to provide relevant information regarding the title question, and it was found that the higher thermodynamic stability of ceph E, relative to ceph F, is caused by an n → π* interaction between a lone electron pair of the oxygen atom of the spiroketal ring (nO) and the antibonding orbital of the carbonyl group (π*C=O). Although similar stereoelectronic interactions have been disclosed in other molecular structures, its presence in ceph E, and very likely in other related naturally occurring products, represents a novel nonanomeric stabilizing effect that should be introduced into the chemical literature.

Radical decarboxylation of L-tryptophan-derived (2S,3aR,8aS)-8-arylsulfonyl-1,2-di(methoxycarbonyl)-1,2,3,3a,8,8a-hexahydro-2H-pyrrolo[2,3-b]indoles 8 and 9 in the presence of diphenyl diselenide results in the endo-selective formation of (2R,3aR,8aS)-8-arylsulfonyl-1-methoxycarbonyl-2-phenylselenyl-1,2,3,3a,8,8a-hexahydro-2H-pyrrolo[2,3-b]indoles 10 and 11. These selenides, in conjunction with Lewis acids, serves as precursors to the corresponding N-acyl iminium ions, which undergo selective endo-face quenching by allyltributylstannane, allyltrimethylsilane, propargyltrimethylsilane, and trimethylsilylcyanide. Stereochemical assignments rest on NMR data and crystallographic studies. The endo-selective nature of these reactions is interpreted in terms of minimization of allylic strain at the transition state for nucleophilic attack on the N-acyl iminum ion.

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