Asymmetric Synthesis of Spiro[Azetidine‐3,3′‐Indoline]‐2,2′‐Diones via Copper(I)‐Catalyzed Kinugasa/C−C Coupling Cascade Reaction

Abstract

Spiro[azetidine-indolines] are important scaffolds in diverse bioactive compounds. Current efforts to synthesize spiro[azetidine-indolines] are limited to chiral spiro[azetidine-2,3'-indolines]. Asymmetric synthesis of structurally similar chiral spiro[azetidine-3,3'-indolines] remains unexplored. In this work, the first copper(I)catalyzed asymmetric Kinugasa/aryl CÀ C coupling cascade reaction is described. This provides a straightforward access to densely functionalized chiral spiro[azetidine-3,3'-indoline]-2,2'-diones in good yields and with high enantioselectivity.

Highly diastereo- and enantioselective synthesis of spiro β-lactams via copper-catalyzed Kinugasa/aldol cascade reaction

“…15 Very recently, we developed a Kinugasa/C–C coupling cascade reaction of ( N -2-iodoary)propiolamides with nitrones for the synthesis of chiral 3,3′-spiro[β-lactam]-oxindoles (Scheme 1b). 16 The choice of propiolamide substrates is crucial for this cascade reaction. The additional amide group from propiolamides can help to inhibit the produce of protonated Kinugasa byproducts and lead to efficient aryl C–C coupling.…”

“…No example to interrupt the Kinugasa reaction with ketones as the nucleophiles for cascade Kinugasa/aldol reaction has been developed. Although chiral control is not a problem in the Kinugasa reaction step, [9][10][11][12][13][14][15][16] the diastereoselective control in the following aldol reaction step may be a great challenge for such cascade reactions. We envisioned that with ketone-tethered propiolamides and nitrones as the substrates, the Kinugasa/aldol cascade reaction will form spirolactam products bearing three contiguous stereogenic centers in one step.…”