The Analysis of Two Distinct Strategies toward the Enantioselective Formal Total Synthesis of (+)-Gelsenicine.

A full account of a formal enantioselective total synthesis of (+)-gelsenicine is described. Separate strategies based on catalytic cycloisomerization as the central step are considered. One plan involves chirality transfer from enantioenriched substrates, while the other employs asymmetric catalysis. The chirality transfer strategy is less effective, while in the latter, phosphoramidite- and bisphosphine-gold complexes are tested and ultimately provide a key intermediate in high enantiopurity in our Gelsemium alkaloid syntheses.

Multigram Synthesis of a Combustion-Relevant δ-Ketohydroperoxide through Sulfonylhydrazine Substitution.

A synthesis of a δ-ketohydroperoxide is described, addressing potential functional-group compatibilities in these elusive species relevant to combustion and atmospheric chemistries. The hydroperoxide is installed via sulfonylhydrazine substitution, which was found to be more effective than displacement of secondary halides. As part of this protocol, it was observed that 1,2-dimethoxyethane is an advantageous medium for the reaction, avoiding the formation of a tetrahydrofuran hydroperoxide side product. This discovery facilitated the multigram synthesis (6 steps, 41 % yield overall) and discrete characterization of the target δ-ketohydroperoxide.

Chirality Transfer and Asymmetric Catalysis: Two Strategies toward the Enantioselective Formal Total Synthesis of (+)-Gelsenicine.

Two strategies are described en route to an enantioselective total synthesis of gelsenicine. One approach centers on a chirality transfer cycloisomerization that ultimately fell short. Separately, an asymmetric catalysis route utilizing bisphosphine-gold-catalyzed cycloisomerization was pursued. A catalytic system was identified that provided a synthetic intermediate in our Gelsemium alkaloid syntheses in high enantiopurity and with absolute configuration determined by electronic circular dichroism, thus representing an enantioselective formal total synthesis of (+)-gelsenicine.