Rh(I)-Catalyzed Enantioselective C-H Bond Arylation: Efficient Access to Planar Chiral Ferrocenyl Thioketones

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Sep 14, 2019
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Planar chiral ferrocenes have been widely employed as ligands or catalysts in asymmetric catalysis since the serendipitous discovery of ferrocene in the early 1950s. Consequently, their asymmetric syntheses are intensively investigated in the past decades. While diastereoselective directed ortho-metalation (DoM), enantioselective DoM, and chiral resolution are the most commonly used approaches, they suffer from either pre-installation of chiral auxiliaries or requirement of stoichiometric external bases, and so on.  

Meanwhile, metal-catalyzed direct functionalization of C-H bonds allows for new and complementary disconnections in synthetic chemistry. In addition to chemo- and regioselectivity issues, an efficient induction of stereochemical information by discriminating the inert enantiotopic C-H bonds is extremely challenging due to the ubiquity of C-H bonds. Nevertheless, significant advances have been achieved in the field of asymmetric C-H functionalization. It has been one of the most innovative fields in the past years.

The research group led by Prof. Shuli You at Shanghai Institute of Organic Chemistry (SIOC) has made remarkable progress in the construction of planar chiral ferrocenes and axially chiral biaryls by employing asymmetric C-H functionalization strategy. Notably, the products of these processes are easily transformed into a variety of chiral catalysts or ligands, which have been demonstrated to promote efficient asymmetric reactions.  

In their recent paper published in Nature Communications, Prof. You and coworkers described a rhodium(I)/phosphonite catalyzed thioketone-directed enantioselective C-H bond arylation of ferrocenes.  

“Last year, we developed a Pd(II)-catalyzed C-H direct arylation of ferrocenes with thioketone as an effective directing group,” said Prof. You, “unfortunately, neither Pd(II)/MPAA nor Pd(II)/chiral phosphate anion catalytic system gave any asymmetric induction.”  

“Surprisingly, in the presence of Rh(I) catalyst introduced by the Glorius group, highly enantioselective C-H arylation reaction proceeded smoothly and a series of planar chiral ferrocenes were obtained in good yields and excellent enantioselectivities (up to 86% yield, 99% ee)” Prof. You further expressed, “Notably, heteroaryl coupled ferrocenes, which are difficult to access with previous approaches, can be obtained in satisfactory results. Moreover, control experiments indicated the unique role of thioketone group in the C-H bond activation process.”  

“We are currently working on mechanistic studies and the applications of products obtained herein in the synthesis of valuable planar chiral ligands/catalysts.” Prof. You concluded.

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Qing Gu

Associate Professor, Shanghai Institute of Organic Chemistry

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