Christopher F. Bender

Gold(I)-catalyzed intramolecular hydroamination of unactivated C==C bonds with alkyl ammonium salts.

A mixture of (5)AuCl [ = PCy2[2-(2,6-C6H3(OMe)2)C6H4]] and AgOTf catalyzes the intramolecular hydroamination of unactivated C==C bonds with primary and secondary ammonium salts.

A Concise Synthesis of Berkelic Acid Inspired by Combining the Natural Products Spicifernin and Pulvilloric Acid

We describe a concise synthesis of the structurally novel fungal extremophile metabolite berkelic acid, an effort leading to an unambiguous assignment of C22 stereochemistry. Our synthetic approach was inspired by the recognition that berkelic acid displays structural characteristics reminiscent of two other fungal metabolites, spicifernin and pulvilloric acid. Based on this notion, we executed a synthesis that features a Ag-catalyzed cascade dearomatization-cycloisomerization-cycloaddition sequence to couple two natural product inspired fragments. Notably, a spicifernin-like synthon was prepared with defined C22 stereochemistry in seven steps and three purifications (24-28% overall yield). A potentially useful anti-selective conjugate propargylation reaction was developed to introduce the vicinal stereodiad. An enantioconvergent synthesis of the other coupling partner, the aromatic precursor to pulvilloric acid methyl ester, was achieved in eight steps and 48% overall yield. The total synthesis of berkelic acid and its C22 epimer was thus completed in a 10 step linear sequence and 11-27% overall yield.

Platinum-catalyzed hydrofunctionalization of unactivated alkenes with carbon, nitrogen and oxygen nucleophiles

The transition metal-catalyzed addition of the X-H bond of a carbon, nitrogen or oxygen nucleophile across the C[double bond]C bond of an unactivated alkene (hydrofunctionalization) represents an attractive, atom-economical approach to the synthesis of carbocyclic and heterocyclic molecules and for the elaboration of ethylene and 1-alkenes. We have developed a family of Pt(II)-catalyzed protocols for the inter- and intramolecular hydrofunctionalization of unactivated alkenes with a range of H-X nucleophiles including beta-diketones, indoles, amines, carboxamides and alcohols. These transformations display good functional group compatibility, low moisture sensitivity, and often good generality.

A biosynthetically inspired synthesis of (−)-berkelic acid and analogs

We describe a complete account of our total synthesis and biological evaluation of (-)-berkelic acid and analogs. We delineate a synthetic strategy inspired by a potentially biomimetic union between the natural products spicifernin and pulvilloric acid. After defining optimal parameters, we executed a one-pot silver-mediated in situ dehydration of an isochroman lactol to methyl pulvillorate, the cycloisomerization of a spicifernin-like alkynol to the corresponding exocyclic enol ether, and a subsequent cycloaddition to deliver the tetracyclic core of berkelic acid. Our studies confirm that the original assigned berkelic acid structure is not stable and equilibrates into a mixture of 4 diastereomers, fully characterized by X-ray crystallography. In addition to berkelic acid, C22-epi-berkelic acid, and nor-berkelic acids, we synthesized C26-oxoberkelic acid analogs that were evaluated against human cancer cell lines. In contrast to data reported for natural berkelic acid, our synthetic material and analogs were found to be devoid of activity.