Synthesis and exploration of electronically modified (R)-5,5-dimethyl-(p-CF_3)_3-i-PrPHOX in palladium-catalyzed enantio- and diastereoselective allylic alkylation: a practical alternative to (R)-(p-CF_3)_3-t-BuPHOX

The synthesis of the novel electronically modified phosphinooxazoline (PHOX) ligand, (R)-5,5-dimethyl-(p-CF_3)_3-i-PrPHOX, is described. The utility of this PHOX ligand is explored in both enantio- and diastereoselective palladium-catalyzed allylic alkylations. These investigations prove (R)-5,5-dimethyl-(p-CF_3)_3-i-PrPHOX to be an effective and cost-efficient alternative to electronically modified PHOX ligands derived from the prohibitively expensive (R)-t-leucine

A Computational Model Relating Structure and Reactivity in Enantioselective Oxidations of Secondary Alcohols by (−)-Sparteine−Pd^(II) Complexes

The key interactions responsible for the unique reactivity of (−)-sparteine−PdX_2 complexes (X = chloride, acetate) in the enantioselective oxidation of secondary alcohols have been elucidated using quantum mechanics (B3LYP DFT with the PBF polarizable continuum solvent model). From examining many possible pathways, we find the mechanism involves:  (1) substitution of the alcohol in place of an X-group, (2) deprotonation of the bound alcohol by the deposed anion and free sparteine, (3) β-hydride elimination through a four-coordinate transition state in which the second anion is displaced but tightly associated, (4) replacement of the ketone product with the associated anion. The enantioselectivities observed under base-rich reaction conditions follow directly from calculated energies of diastereomeric β-hydride elimination transition states incorporating (R) and (S) substrates. This relationship reveals an important role of the anion, namely to communicate the steric interaction of the ligand on one side of the PdII square plane and the substrate on the other side. When no anion is included, no enantioselectivity is predicted. Locating these transition states in different solvents shows that higher dielectrics stabilize the charge separation between the anion and metal and draw the anion farther into solution. Thus, the solvent influences the barrier height (rate) and selectivity of the oxidation

Polycyclic Furanobutenolide-Derived Cembranoid and Norcembranoid Natural Products: Biosynthetic Connections and Synthetic Efforts

The polycyclic furanobutenolide-derived cembranoid and norcembranoid natural products are a family of congested, stereochemically complex, and extensively oxygenated polycyclic diterpenes and norditerpenes. Although the elegant architectures and biological activity profiles of these natural products have captured the attention of chemists since the isolation of the first members of the family in the 1990s, the de novo synthesis of only a single polycyclic furanobutenolide-derived cembranoid and norcembranoid has been accomplished. This article begins with a brief discussion of the proposed biosyntheses and biosynthetic connections among the polycyclic furanobutenolide-derived cembranoids and norcembranoids and then provides a comprehensive review of the synthetic efforts toward each member of the natural product family, including biomimetic, semisynthetic, and de novo synthetic strategies. This body of knowledge has been gathered to provide insight into the reactivity and constraints of these compact and highly oxygenated polycyclic structures, as well as to offer guidance for future synthetic endeavors