Total synthesis of (+)-camptothecin

A total synthesis of (+)-camptothecin is described. The approach is based on a room temperature LUMOdiene-controlled Diels–Alder cycloaddition of the electron deficient N-sulfonyl-1-aza-1,3-butadiene with the electron rich dienophile 1,1,3,3-tetraethoxypropene () for assembly of a pyridine precursor to the D-ring pyridone. The 20(S) tertiary alcohol was installed through a Sharpless asymmetric dihydroxylation reaction on the methyl vinyl ether , using the 3,4,5-trimethoxyphenyl-derived pyrimidine DHQ dimer ligand . In a single reaction vessel, the C and E rings were closed using an acid-catalyzed deprotection of the benzylic ethers to afford the corresponding benzylic bromides () which underwent intramolecular nucleophilic displacement by the carboxylate and pyridone nitrogen to furnish (+)-camptothecin.