title: Total synthesis of (-)-colchicine via a Rh-triggered cycloaddition cascade.
abstract: [reaction: see text] A synthesis of the antimitotic alkaloids (-)-colchicine and (-)-isocolchicine is reported. Important steps are (a) enantioselective transfer-hydrogenation of an alkynone, (b) iodine/magnesium exchange with subsequent aromatic acylation, (c) Rh-catalyzed transformation of an alpha-diazoketone into an oxatetracyclic key intermediate through intramolecular [3 + 2]-cycloaddition of an in situ generated carbonyl ylide, and (d) regioselective conversion of the cycloadduct into a tropolone derivative. The new synthetic strategy opens an efficient enantioselective access to colchicine and structural analogues.
authors.affiliation: Universität zu Köln, Greinstrasse 4, D-50939 Köln, Germany.
authors.forename: Timm
authors.initials: T
authors.lastname: Graening
authors.forename: Virginie
authors.initials: V
authors.lastname: Bette
authors.forename: Jörg
authors.initials: J
authors.lastname: Neudörfl
authors.forename: Johann
authors.initials: J
authors.lastname: Lex
authors.forename: Hans-Günther
authors.initials: HG
authors.lastname: Schmalz
mesh_terms: D003078:Colchicine / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D003500:Cyclization; D008958:Models, Molecular; D015394:Molecular Structure; D012238:Rhodium / Q000737:chemistry*
chemical_list: D012238:Rhodium; D003078:Colchicine