Evolution of a synthetic strategy: total synthesis of (+/-)-welwitindolinone A isonitrile.
An efficient and highly stereoselective total synthesis of the natural product (+/-)-welwitindolinone A isonitrile (1) is described. The bicyclo[4.2.0]octane core of 1 was established by a regio- and diastereoselective [2+2] ketene cycloaddition. The C12 quaternary center and vicinal stereogenic chlorine were installed in a single operation with excellent stereocontrol via a chloronium ion mediated semipinacol rearrangement. Described strategies for construction of the spiro-oxinole include a SmI2-LiCl mediated reductive cyclization and a novel anionic cyclization that simultaneously constructs the spiro-oxindole and vinyl isonitrile moieties.
Reisman
Sarah E
SE
Sterling Chemistry Laboratory, Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, USA.
Ready
Joseph M
JM
Weiss
Matthew M
MM
Hasuoka
Atsushi
A
Hirata
Makoto
M
Tamaki
Kazuhiko
K
Ovaska
Timo V
TV
Smith
Catherine J
CJ
Wood
John L
JL
D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D003500:Cyclization; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry; D008968:Molecular Conformation; D009795:Octanes / Q000737:chemistry*; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
D001643:Bridged Bicyclo Compounds; D026121:Indole Alkaloids; D007211:Indoles; D007659:Ketones; D009795:Octanes; D013141:Spiro Compounds; C527897:welwitindolinone A isonitrile