title: Expeditious and Divergent Total Syntheses of Aspidosperma Alkaloids Exploiting Iridium(I)-Catalyzed Generation of Reactive Enamine Intermediates.
abstract: A new approach for the divergent total syntheses of (±)-vincaminorine, (±)-N-methylquebrachamine, (±)-quebrachamine, (±)-minovine and (±)-vincadifformine, each in less than 10 linear steps starting from a single δ-lactam building block, is reported. Key to our route design is the late-stage generation of reactive enamine functionality from stable indole-linked δ-lactams via a highly chemoselective iridium(I)-catalyzed reduction. The efficiently formed secodine intermediates subsequently undergo either a formal Diels-Alder cycloaddition or a competitive Michael addition/reduction to access aspidosperma-type alkaloids in excellent diastereoselectivities. Product selectivity could be controlled by changing the indole N-protecting group in the reductive cyclization precursors. An asymmetric variant of this synthetic strategy for the synthesis of (+)-20-epi-ibophyllidine is also described.
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, UK.|Organic Chemistry, Institute of Chemical and Engineering Sciences, 8 Biomedical Grove, Neuros, #07-01, Singapore, 138665, Singapore.
authors.forename: Peng Wen
authors.initials: PW
authors.lastname: Tan
authors.affiliation: Organic Chemistry, Institute of Chemical and Engineering Sciences, 8 Biomedical Grove, Neuros, #07-01, Singapore, 138665, Singapore. jayasree_seayad@ices.a-star.edu.sg.
authors.forename: Jayasree
authors.initials: J
authors.lastname: Seayad
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, UK. darren.dixon@chem.ox.ac.uk.
authors.forename: Darren J
authors.identifier: 0000-0003-2456-5236
authors.initials: DJ
authors.lastname: Dixon
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry*; D030009:Aspidosperma / Q000737:chemistry*; D002384:Catalysis; D061565:Cycloaddition Reaction; D007495:Iridium / Q000737:chemistry*; D015394:Molecular Structure
chemical_list: D000470:Alkaloids; D000588:Amines; D007495:Iridium
keywords: aspidosperma alkaloid; enamine; iridium catalyzed reduction; lactam; total synthesis