Development of the Regiodivergent Asymmetric Prenylation of 3‐Substituted Oxindoles

Abstract

This paper fully describes our efforts to design a Pd-catalyzed asymmetric prenylation of 3-substituted oxindoles that affords access to both the linear and reverse-prenylated products. Both 3-alkyl- and 3-aryloxindoles performed well under our optimized reaction conditions. The regiodivergent alkylation of monoterpene-derived electrophiles using this methodology was also investigated. The utility of this methodology in natural product synthesis was demonstrated through the efficient total syntheses of four Flustra alkaloids, which also allowed the absolute stereochemistry of the prenylated oxindole products to be assigned. Surprisingly, the same enantiomer of ligand produced linear and branched regioisomers of opposite chirality.

Enantioselective Synthesis of Vicinal All‐Carbon Quaternary Centers via Iridium‐Catalyzed Allylic Alkylation

“…[1] However,o wing to significant progress in this area over recent decades, [2] the more formidable challenge of constructing vicinal all-carbon quaternary centers has become the forefront of investigation. Al imited number of organic [3] and transition-metal-catalyzed [4,5] methods for the enantioselective preparation of vicinal all-carbon quaternary stereocenters have been reported, [6] with enantioselective transition-metal-catalyzed allylic alkylation strategies remaining underexplored.…”

Catalytic, contra-Thermodynamic Alkene Isomerization

“…For example, indanone (+)-28a -obtained in >99% e.e. using a Pd-catalyzed asymmetric prenylation 30 -reacted to form homoallyl isomer (+)-28a in 63% isolated yield.…”

Enantioselective Synthesis of Vicinal All‐Carbon Quaternary Centers via Iridium‐Catalyzed Allylic Alkylation

“…In 2011, Trost and co‐workers reported an enantioselective palladium‐catalyzed allylic alkylation of oxindoles to provide reverse prenylated products containing a homoallylic quaternary stereocenter vicinal to an all‐carbon quaternary center (Figure A) ,. In 2014, the groups of Ooi and Zhang each disclosed examples of enantio‐ and diastereoselective palladium‐catalyzed allylic alkylation reactions to form cyclic products bearing vicinal all‐carbon quaternary stereocenters (Figure B).…”