It Is Not Just Up to the Substrate: Palladium(0) Cyclizes Nazarov Substrates through Intramolecular Allylic Alkylation

5 years ago

It Is Not Just Up to the Substrate: Palladium(0) Cyclizes Nazarov Substrates through Intramolecular Allylic Alkylation

Gabriela M. Martinez, Tülay A. Ateşin, David Flores

Plausible mechanisms of Pd⁰-catalyzed cyclization of diketoesters were modeled using density functional theory calculations. Comparison of the reaction mechanisms of uncatalyzed and Pd⁰-catalyzed cyclizations revealed the vital role of the Pd⁰ catalyst. Both reactions favor a stepwise mechanism involving a proton transfer followed by carbon–carbon bond formation over either the reverse order or a concerted mechanism. The key step for the Pd⁰-catalyzed reaction is the formation of a relatively stable intermediate, an η³-allyl Pd^II complex, in the lowest energy pathway. Our proposed mechanism is consistent with a Pd⁰-catalyzed intramolecular allylic alkylation reaction, previously referred to as “Nazarov-type” reactions. It is worth noting that, in contrast to many allylic alkylations, the Pd⁰-catalyzed cyclization does not require any additional reagents or an activated leaving group to form an η³-allyl Pd^II complex; thus, the α-hydroxycyclopentenone is produced from diketoesters with no waste. Furthermore, the asymmetric version of this reaction is the first known example of the use of an allylic alkylation reaction for the synthesis of a chiral cyclopentenone unit.

Publisher URL: http://dx.doi.org/10.1021/acs.organomet.7b00494

DOI: 10.1021/acs.organomet.7b00494