title: Catalytic enantioselective amide allylation of isatins and its application in the synthesis of 2-oxindole derivatives spiro-fused to the α-methylene-γ-butyrolactone functionality.
abstract: This article is a full account of the work exploring the potential utility of catalytic enantioselective amide allylation of various isatins using indium-based chiral catalysts. A survey of various isatin substrates and NH-containing stannylated reagents revealed that the reaction has a remarkably wide scope to result in extremely high yields and enantioselectivities (up to >99 %, 99 % ee) of variously substituted homoallylic alcohols. Several mechanistic investigations demonstrated that the substrate-reagent hydrogen-bond interaction plays a critical role in the formation of the key transition states to result in enhanced catalytic reaction. The success of this approach allowed convenient access to chiral 2-oxindoles spiro-fused to the α-methylene-γ-butyrolactone functionality and their halogenated derivatives in almost enantiopure forms, thus highlighting the general utility of this synthetic method to deliver a large variety of antineoplastic drug candidates and pharmaceutically meaningful compounds.
authors: Department of Applied Chemistry, Graduate School of Engineering, Shizuoka University, 3-5-1 Johoku, Naka-ku, Hamamatsu 432-8561 (Japan), Fax: (+81) 53-478-1150.
authors: Masaki
authors: M
authors: Takahashi
authors: Yusuke
authors: Y
authors: Murata
authors: Fumitoshi
authors: F
authors: Yagishita
authors: Masami
authors: M
authors: Sakamoto
authors: Tetsuya
authors: T
authors: Sengoku
authors: Hidemi
authors: H
authors: Yoda
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry; D000577:Amides / Q000737:chemistry*; D002384:Catalysis; D007211:Indoles / Q000737:chemistry*; D007510:Isatin / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D000078183:Oxindoles; D013141:Spiro Compounds / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000577:Amides; D007211:Indoles; D000078183:Oxindoles; D013141:Spiro Compounds; C022960:2-oxindole; C014096:alpha-methylene gamma-butyrolactone; D007510:Isatin; D015107:4-Butyrolactone
keywords: allylation; antitumor agents; asymmetric catalysis; lactones; spiro compounds