Catalytic Cyclooligomerization of Enones with Three Methylene Equivalents

Cyclic structures
are highly represented in organic molecules,
motivating a wealth of catalytic methods targeting their synthesis.
Among the various ring-forming processes, cyclooligomerization reactions
possess several attractive features but require addressing a unique
challenge associated with controlling ring-size selectivity. Here
we describe the catalytic reductive cocyclooligomerization of an enone
and three carbene equivalents to generate a cyclopentane, a process
that constitutes a formal [2 + 1 + 1 + 1]-cycloaddition. The reaction
is promoted by a (quinox)Ni catalyst and uses CH2Cl2/Zn as the C1 component. Mechanistic studies are
consistent with a metallacycle-based pathway, featuring sequential
migratory insertions of multiple carbene equivalents to yield cycloalkanes
larger than cyclopropanes.