| Abstract
| - The asymmetric synthesis of (−)-(R)-pyrrolam A was achieved in three operations from N-Bocpyrrolidine via an α-(N-carbamoyl)alkylcuprate vinylation reaction followed by N-Boc deprotectionand cyclization. One-pot deprotection−cyclization procedures led to mixtures of pyrrolam A andits double bond isomers. These isomerization events could be circumvented by use of a two-stepprocedure. To guide aspects of the experiments, a series of computational energy evaluations andchemical shift predictions were performed with molecular mechanics, semiempirical, ab initio, anddensity functional methods. The relative stabilities of the double bond isomers, as estimated byexperiment, challenged a number of computational methods, and only the MP2 model with itsmoderate degree of electron correlation came close to matching the experimental data. The MP2method was further applied to an unusual aspect of the double bond migration between pyrrolamA and its isomer 9. The reaction (1 to 9) on neat samples is irreversible without racemization, andthe alumina-mediated equilibration is accompanied by complete loss of enantiomeric excess. Thesource of the irreversibility was traced to asymmetric charge distribution in the intermediatedienolate anion. The analysis ultimately led to a semiquantitative sketch of the pyrrolam energysurface.
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