Highly Enantioselective Intermolecular Rauhut-Currier Reaction of Activated Alkenes Catalyzed by Multifunctional Chiral Phosphine

The Rauhut-Currier (R-C) reaction, first disclosed by Rauhut and Currier in 1963, is an atom economy strategy for the construction of carbon-carbon bond and a wide range of synthetic valuable building blocks. During the past few decades, significant progress on the enantioselective intramolecular R-C reactions has been achieved by utilizing diverse chiral nucleophilic catalysts such as cysteine derivatives, L-prolinol, hydrogen-bonding catalyst and beta-aminephosphine. However, compared to the well-developed enantioselective intramolecular R-C reactions, the enantioselective cross intermolecular R-C reaction concerning two different alkenes has been rarely explored so far. The enantioselective cross R-C reaction still suffers from a series of drawbacks such as low reactivity, enantioselectivity, limited substrate scope and higher catalyst loading. Thus, the development of novel chiral nucleophilic catalyst, for highly enantioselective cross R-C reaction is highly desirable. In this article, we wish to report the application of Xiao-Phos in the highly enantioselective cross intermolecular R-C reaction of vinyl ketone and activated alkenes. Accordingly, a stirred solution of 3-aroyl acrylates 1 (0.2 mmol) and (S,R-s)-X8 (0.02 mmol) in toluene (2 mL) was cooled to -20 degrees C. Subsequently, vinyl ketone 2 (0.4 mmol for aryl vinyl ketone and).6 mmol for alkyl vinyl ketone) was added in one portion through a syringe. The mixture was stirred at this temperature until completion of 3-aroyl acrylate as indicated by TLC. After completion of the reaction, the reaction mixture was directly purified by silica gel chromatography to afford the desired RC product. What's more, control experiments demonstrated that the presence of free sulfinamide N-H in Xiao-Phos is crucial for the enantioselective cross R-C reaction. Finally, for more details about (S,Rs)-X8 in the enantioselective cross R-C reaction, control experiments monitored by P-31 NMR spectroscopy were conducted and the P-31 NMR expenments indicated that this cross intermolecular R-C reaction was initiated by the Michael addition of (S,R-s)-X8 to vinyl ketone 2.