Trapping of Oxonium Ylide with Isatins:  Efficient and Stereoselective Construction of Adjacent Quaternary Carbon Centers

Abstract

The 3-substituted 3-hydroxyindolin-2-ones with adjacent quaternary stereocenters were constructed in a single step via an efficient and stereoselective trapping of oxonium ylide with isatins. This reaction proceeds well in supercritical CO2 and is an example of the ability to use green approaches to efficiently construct polyfunctional molecules.

Facile Creation of 3-Substituted-3-Hydroxy-2-Oxindoles by Arginine-Catalyzed Aldol Reactions of α,β-Unsaturated Ketones with Isatins

“…Incorporating protecting groups on the N1 of oxindole had no effect on reactivity, and gave the desired product in almost quantitative yield (99%) ( Table 2, entry 16). However, the electronic properties of the substituents at the isatin affected the yields strongly ( Table 2, entries [17][18][19][20]. Isatin with an electrondonating group only gave 60% yield.…”

“…Owing to the significance of this structural motif, numerous elegant synthetic methodologies have been developed [13][14][15][16][17][18][19][20][21] and aim to facilitate the synthesis of sufficient quantities of the desired natural products and related analogues for biological evaluation and structure-activity relationship studies, and thus finally contribute to the development of new therapeutic agents or important biological tools. The most direct approach to 3-substituted-3-hydroxy oxindoles is a nucleophilic addition of appropriate nucleophiles to isatins, such as the aldol reaction or an alkylation of isatins.…”

Catalytic Enantioselective Trapping of an Alcoholic Oxonium Ylide with Aldehydes: RhII/ZrIV‐Co‐Catalyzed Three‐Component Reactions of Aryl Diazoacetates, Benzyl Alcohol, and Aldehydes

“…Trapping intermediates II with aldehydes resulted in 4; the desired process was in competition with an irreversible intramolecular proton transfer within IIa/IIb leading to the OÀH insertion side products 5 (Scheme 1). We also observed that addition of a stoichiometric amount of the Lewis acid Ti(OtBu) 4 suppressed the OÀH insertion.…”

“…[4c] The reaction was proposed to proceed through the alcoholic oxonium ylide intermediates IIa or IIb (Scheme 1), which are generated in situ from 1 and benzyl alcohol (2) in the presence of Rh 2 (OAc) 4 . Trapping intermediates II with aldehydes resulted in 4; the desired process was in competition with an irreversible intramolecular proton transfer within IIa/IIb leading to the OÀH insertion side products 5 (Scheme 1).…”

“…The Kobayashi research group has developed air-stable, chiral Zr/binol/molecular sieves catalysts by combining Zr-(OnBu) 4 , chiral binol ligands 6, and 5 molecular sieves (M.S.) in appropriate quantities.…”