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

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 PdII 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 PdII 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.

本研究采用密度泛函理论（density functional theory）计算，对二酮酯的零价钯（Pd⁰）催化环化反应的合理机理进行了建模。通过对比无催化与零价钯催化环化反应的机理，揭示了零价钯催化剂的关键作用。两类反应均倾向于分步机理，即先发生质子转移再形成碳-碳键，而非逆向顺序或协同机理。零价钯催化反应的最低能量路径中，关键步骤为生成相对稳定的中间体——η³-烯丙基钯(II)（η³-allyl PdII）配合物。我们提出的机理与零价钯催化的分子内烯丙基烷基化反应（此前被称为“Nazarov型”反应）相符。值得注意的是，与多数烯丙基烷基化反应不同，该零价钯催化环化反应无需额外试剂或活化离去基团即可生成η³-烯丙基钯(II)配合物；因此可由二酮酯直接合成α-羟基环戊烯酮（α-hydroxycyclopentenone），无废弃物生成。此外，该反应的不对称变体是目前已知首例利用烯丙基烷基化反应合成手性环戊烯酮结构单元的实例。