Enantioselective total synthesis of (-)-acylfulvene and (-)-irofulven.
We report our full account of the enantioselective total synthesis of (-)-acylfulvene (1) and (-)-irofulven (2), which features metathesis reactions for the rapid assembly of the molecular framework of these antitumor agents. We discuss (1) the application of an Evans Cu-catalyzed aldol addition reaction using a strained cyclopropyl ketenethioacetal, (2) an efficient enyne ring-closing metathesis cascade reaction in a challenging setting, (3) the reagent IPNBSH for a late-stage reductive allylic transposition reaction, and (4) the final RCM/dehydrogenation sequence for the formation of (-)-acylfulvene (1) and (-)-irofulven (2).
Siegel
Dustin S
DS
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Piizzi
Grazia
G
Piersanti
Giovanni
G
Movassaghi
Mohammad
M
D000498:Allyl Compounds / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
D000498:Allyl Compounds; D000970:Antineoplastic Agents; D012717:Sesquiterpenes; D013141:Spiro Compounds; C079422:acylfulvene; C102714:irofulven; D003300:Copper; D006859:Hydrogen