Au(I)/Chiral Tertiary Amine Catalyzed Tandem Olefination/Asymmetric Cyclization Reaction to Quaternary Spirocyclic Oxindoles

We report an asymmetric tandem reaction realized by sequential Au(I)/chiral bifunctional tertiary amine catalysis. A tandem olefmation/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% IPrAuBF4, readily afforded 3-alkenyloxindoles for the subsequent Michael/Michael addition of 2-tosylaminochalcone catalyzed by 5.0 similar to 10.0 mol% chiral bifunctional tertiary amine-squaramide Cl. 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 CH2Cl2 (1.0 mL). The resulting mixture was stirred at 25 C for 0.5 h and then cooled down to 0 degrees C. After ethers 2 (1.5 equiv.) was added in one-portion, a solution of diazooxindoles 1 in 1.5 mL of CH2Cl2 was added slowly by a syringe pump in 20 minutes. The reaction was stirred at 0 degrees C till full consumption of 1 by TLC analysis. After the successive addition of Cl and 4 (1.1 equiv.), the reaction was warmed to 25 degrees C and stiffed 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 H-1 NMR analysis of the crude reaction mi xture. 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.