Synthesis of Highly Oxygenated Carbocycles by Stereoselective Coupling of Alkynes to 1,3- and 1,4-Dicarbonyl Systems

Densely
substituted and highly oxygenated carbocycles are challenging
targets for synthesis. In particular, those possessing numerous contiguous,
fully substituted carbon atoms (i.e., tertiary alcohols and quaternary
centers) are often not accessible in a direct fashion, necessitating
the strategic decoupling of ring-formation from the establishment
of functionality about the system. Here, we describe an approach to
the construction of highly oxygenated mono-, di-, and polycyclic carbocycles
from the reaction of disubstituted alkynes with β- or γ-dicarbonyl
systems. These processes embrace a variant of metallacycle-mediated
annulation chemistry where initial alkyne–carbonyl coupling
is followed by a second, now intramolecular, stereo­selective
C–C bond-forming event. In addition to revealing the basic
reactivity pattern in intermolecular settings, we demonstrate that
this class of reactivity is quite powerful in a fully intramolecular
context and, when terminated by a stereo­selective oxidation
process, can be used to generate polycyclic systems containing a fully
substituted and highly oxygenated five-membered ring.