Enantioselective Approach to Polycyclic Polyprenylated Acylphloroglucinols via Catalytic Asymmetric Intramolecular Cyclopropanation

The formal enantioselective
total synthesis of nemorosone, garsubellin A, clusianone, and hyperforin
is described. The catalytic asymmetric intramolecular cyclopropanation
(CAIMCP) of an α-diazo ketone, a common synthetic intermediate
for the above four polycyclic polyprenylated acylphloroglucinols previously
reported by us, exhibited low enantioselectivity. However, CAIMCP
of the corresponding α-diazo β-keto sulfone afforded the
desired product in 79% yield with 84% ee. Investigation of the CAIMCP
of the α-diazo β-keto sulfone demonstrated the formation
of a rearrangement product in the presence of molecular sieves 4 Å,
whereas, in the presence of H2O, the byproduct derived
from ring-opening of the desired cyclopropane was observed. X-ray
crystallographic analysis suggested that the above two products are
derived from the same chiral intermediate. The product derived from
ring-opening of the cyclopropane was successfully transformed to the
respective synthetic intermediates for the total syntheses of nemorosone,
garsubellin A, clusianone, and hyperforin, which had previously been
reported by us.