Au(I)/手性双功能叔胺催化实现的一锅法串联成烯/不对称环化反应构建螺环季碳氧化吲哚

We report an asymmetric tandem reaction realized by sequential Au(I)/chiral bifunctional tertiary amine catalysis. A tandem olefination/asymmetric cyclization reaction is developed, allowing facile synthesis of quaternary spirocyclic oxindoles in good yields and stereoselectivities from N-Ac protected diazooxindoles 1, monofluorinated enol silyl ethers 2 and 2-tosylaminochalcone 4. The initial cross coupling reaction of diazooxindole and fluorinated enol silyl ethers, catalyzed by 3.0 mol% IPrAuBF ₄ , readily afforded 3-alkenyloxindoles for the subsequent Michael/Michael addition of 2-tosylaminochalcone catalyzed by 5.0~10.0 mol% chiral bifunctional tertiary amine-squaramide C1. The tandem reaction was performed by the following general procedure. Under an atmosphere of N ₂ , to an oven-dried Schlenk tube were added IPrAuCl (6.0 mg, 0.0099 mmol, 3.3 mol%) and AgBF ₄ (1.8 mg, 0.0090 mmol, 3.0 mol%), followed by anhydrous CH ₂ Cl ₂ (1.0 mL). The resulting mixture was stirred at 25℃ for 0.5 h and then cooled down to 0℃. After ethers 2 (1.5 equiv.) was added in one-portion, a solution of diazooxindoles 1 in 1.5 mL of CH ₂ Cl ₂ was added slowly by a syringe pump in 20 minutes. The reaction was stirred at 0℃ till full consumption of 1 by TLC analysis. After the successive addition of C1 and 4 (1.1 equiv.), the reaction was warmed to 25℃ and stirred till full consumption of 3, and the mixture was directly subjected to the column chromatography by using petroleum ether/dichloromethane (1/2.5, V/V) as the eluent to give the desired spirocyclic oxindoles 5. The diastereoselectivities of 5 (>20:1) were determined by ¹ H NMR analysis of the crude reaction mixture. The key step of this tandem sequence is the cross coupling reaction of monofluorinated enol silyl ethers and donor-acceptor diazo reagents. We further examined the substrates scope of acyclic aryl diazoacetates and fluorinated enol silyl ethers by using 1.0 mol% IPrAuSbF ₆ as catalyst, providing a new method for the efficient synthesis of trisubstituted alkenes.