Fusicoccin synthesis by intramolecular [4+4] photocycloaddition of 2-pyridones: Stereocontrol of the cycloaddition and elaboration of the pentacyclicproduct

Intramolecular photocycloaddition of a three-carbon tethered pyrindinone-py ridone system yields the 5-8-5 ring system of the fusicoccin/ophiobolin/cer oplastol families. The stereoselectivity of the cycloaddition was found to be dependent on nitrogen substitution; N-methylation led to exclusively tra ns products while an absence of nitrogen substitution resulted in solvent-d ependent stereoselectivity. Solvent and concentration effects for this cycl oaddition were consistent with a hydrogen-bonded dimer that enforces a pro- cia conformation in nonpolar solvents and at higher concentrations. The cis -isomer, a fusicoccin synthesis intermediate, underwent a Cope rearrangemen t at ambient temperature but could be trapped efficiently as the mono epoxi de, yielding a product with six new stereogenic centers. A four-step transf ormation of an amide carbonyl to a methyl group was achieved using a carbam oyl group to activate the amide for cleavage.