Total synthesis of aigialomycin D: surprising chemoselectivity dependence on alkyne structure in nickel-catalyzed cyclizations.
The total synthesis of aigialomycin D was carried out using a nickel-catalyzed ynal macrocyclization as a key step. This key step allowed macrocycle assembly and formation of a disubstituted alkene and a secondary hydroxyl stereocenter in a single step, although the stereocenter was formed unselectively. An interesting side reaction involving five-membered-ring synthesis by an aldehyde/styrene cyclization was observed when macrocyclization of an alkynyl silane was attempted. A mechanistic basis for this surprising process is provided.
Chrovian
Christa C
CC
Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
Knapp-Reed
Beth
B
Montgomery
John
J
D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry; D000480:Alkynes / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D005658:Fungi / Q000737:chemistry; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009532:Nickel / Q000737:chemistry*
D000475:Alkenes; D000480:Alkynes; D018942:Macrolides; C452445:aigialomycin D; D009532:Nickel