Pd(II)/β-ICD-Cocatalyzed Asymmetric Route to Oxindole Scaffold via Cascade Reaction of Diazoacetamides and MBH-Carbonates

Abstract

We report an efficient method for asymmetric synthesis of chiral oxindoles. Allyl palladium(II) chloride dimer (APC)-catalyzed, in combination with β-isocupreidine (β-ICD)-cocatalyzed, reaction of diazoacetamide with Morita-Baylis-Hillman (MBH) carbonates proves to be a facile protocol to access multifunctional oxindoles bearing a C-3 quaternary stereo center. This tandem reaction tolerates a wide variety of functional groups on the both aromatic rings. This method delivers a variety of chiral oxindoles in 50-75% yield and with up to 95:5 dr in most cases along with up to 93:7 er.

Recent advances in Pd-catalyzed asymmetric cyclization reactions

“…Using β-isocupreidine (β-ICD) as a co-catalyst, an asymmetric Pd( ii )-catalyzed cascade reaction between diazoacetamides 783 and MBH carbonates 784 that allowed convenient access to a series of multifunctional oxindoles 785 bearing a C-3 quaternary stereocenter, was disclosed by Hu's group in 2016 (Scheme 184). 355 This tandem reaction tolerated a wide range of substituents on both the aromatic rings, leading to chiral oxindoles with up to 86% ee. Notably, this reaction involved the formation of two key intermediates: one was zwitterion intermediate Int-A generated by C–H insertion reaction, and the other was a chiral MBH ammonium cation intermediate Int-B via nucleophile attack of β-ICD on MBH carbonate.…”

Trapping of Transient Zwitterionic Intermediates by N-Acylpyridinium Salts: A Palladium-Catalyzed Diastereoselective Three-Component Reaction

“…We first investigated the reaction of unsubstituted pyridine 1a with N -aryldiazoamide 3a under the catalysis of [PdCl­(η 3 -C 3 H 5 )] 2 (Table ). Pyridine 1a was converted to N -carbobenzoxy pyridinium salts 2a in situ with benzyl chloroformate (Cbz-Cl) in CH 2 Cl 2 before adding the metal catalyst and 3a .…”

Asymmetric Construction of 3,3-Disubstituted Oxindoles Bearing Vicinal Quaternary–Tertiary Carbon Stereocenters Catalyzed by a Chiral-at-Rhodium Complex

“…Optical active 3,3-disubstituted oxindoles are highly valuable building blocks for biologically active natural products and pharmaceuticals . Consequently, their synthesis, in particular catalytic asymmetric approaches, have attracted significant attention over the past decades. − Of them, the Mannich-type reaction of isatin-derived ketimines with different nucleophiles provides an efficient route to chiral 3,3-disubstituted oxindoles containing a 3-amino substituent in addition to adjacent quaternary–tertiary carbon stereocenters . The construction of such stereogenic centers remains a challenging task in organic synthesis, presumably owing to the steric congestion around the stereocenters .…”