Catalytic asymmetric synthesis of quaternary carbons bearing two aryl substituents. Enantioselective synthesis of 3-alkyl-3-aryl oxindoles by catalytic asymmetric intramolecular heck reactions.
A practical sequence involving three consecutive palladium(0)-catalyzed reactions has been developed for synthesizing 3-alkyl-3-aryloxindoles in high enantiopurity. The Heck cyclization precursors 10 and 11a-k are generated in one step by chemoselective Stille cross-coupling of 2'-triflato-(Z)-2-stannyl-2-butenanilide 9 with aryl or heteroaryl iodides. The pivotal catalytic asymmetric Heck cyclization step of this sequence takes place in high yield and with high enantioselectivity (71-98% ee) with the Pd-BINAP catalyst derived from Pd(OAc)(2) to construct oxindoles containing a diaryl-substituted all-carbon quaternary carbon center. A wide variety of aryl and heteroaryl substituents, including ones of considerable steric bulk, can be introduced at C3 of oxindoles in this way (Table 4). The only limitations encountered to date are aryl substituents containing ortho nitro or basic amine functionalities and the bulky N-alkyl-7-oxindolyl group. Asymmetric Heck cyclization of butenalide 22 having an o-(N-acetyl-N-benzylamino)phenyl substituent at C2 provided a approximately 1:1 mixture of amide atropisomers 23 and 24 in high yield and high enantioselectivity. These atropisomers are formed directly upon Heck cyclization of 22 at 80 degrees C, as they interconvert thermally to only a small extent at this temperature.
Dounay
Amy B
AB
Department of Chemistry, 516 Rowland Hall, University of California, Irvine 92697-2025, USA.
Hatanaka
Keiko
K
Kodanko
Jeremy J
JJ
Oestreich
Martin
M
Overman
Larry E
LE
Pfeifer
Lance A
LA
Weiss
Matthew M
MM
D002384:Catalysis; D003500:Cyclization; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis / Q000737:chemistry*; D007211:Indoles / Q000138:chemical synthesis*; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism
D006841:Hydrocarbons, Aromatic; D007211:Indoles