Nat. Commun.: new progress has been made in the synthesis of planar chiral ferrocene

Author: Recently, the research group of youshuli, Shanghai Institute of organic science, Chinese Academy of Sciences, has made new progress in the synthesis of planar chiral ferrocene by asymmetric C-H bond activation, realized the thiocarbonyl oriented rhodium catalyzed asymmetric C-H bond arylation of ferrocene, and synthesized a series of planar chiral ferrocene compounds efficiently Relevant research results were published in naturecommunications (DOI: 10.1038 / s41467-019-12181-x) under the title of "thouketone-directed rhodium (I) catalyzed enablioselectivec-h bond arrangement of delegates" The first author of this work is Dr Cai Zhongjian, the corresponding author is researcher you Shuli and associate researcher Gu Qing The research was supported by national key R & D plan, National Natural Science Foundation, pilot B program of Chinese Academy of Sciences and basic research program of Shanghai Science and Technology Commission Planar chiral ferrocene has been widely studied as a chiral ligand or catalyst in asymmetric catalysis It is one of the most simple and efficient methods to construct planar chiral ferrocene by using asymmetric C-H bond functionalization strategy In the C-H bond functionalization, the functional groups containing oxygen, nitrogen and phosphorus are the most common guiding groups, but the functional groups containing sulfur atoms are less as guiding groups, even though they are common in many natural products, drug molecules and functional materials In 2018, youshuli research group reported the palladium catalyzed C-H bond arylation of thioketone guided ferrocene Under simple and mild conditions, the reaction can yield a series of excellent ferrocene (angel Chem Int ed 2018, 57, 1296) In view of the wide application of planar chiral ferrocenes, our group hopes to control the enantioselectivity of the reaction by adding chiral ligands However, it is a pity that the asymmetric catalysis of this reaction can not be realized by the addition of single protected chiral amino acid (MPAA) or chiral phosphoric acid Recently, they found that [Rh (C 2H 4) 2Cl] 2 and taddol framework derived phosphine ligand L7 can be used as catalysts to synthesize a series of planar chiral ferrocene compounds with excellent yield and enantioselectivity (up to 86% yield and 99% ee) at 80 ℃ The reaction has a wide range of substrates, and can be well carried out for aryl iodides with different substituents, even heterocyclic aryl iodides (Fig 1) The product (1.56 g) can still be obtained with 86% yield and 96% ee by extending the standard reaction to the scale of gram When the product 3A reacts with Ag 2CO 3, it can be converted into carbonyl substitution product in 93% yield, and the EE value remains unchanged (Fig 2) Fig 1 asymmetric C-H bond arylation of ferrocene catalyzed by thiocarbonyl rhodium (source: Nat Commun.) Fig 2 gram scale reaction and product conversion (source: Nat Commun.) in order to understand the reaction mechanism in depth, the author has done some mechanism and control experiments (Fig 3) When keto carbonyl is used as the guiding group, the reaction can not take place at all, more than 95% of the raw materials are retained (EQ 1), which indicates that thiocarbonyl plays a key role in the activation of C-H bond At the same time, a series of competitive experiments have been carried out It is found that the reaction activity of electron deficient iodoaromatic is higher than that of electron donor (EQ 2,4-methoxyiodobenzene: yield 11%; 4-cyanodiobenzene: yield 25%) Under the standard conditions, the H / D exchange (EQ 3) of thiocarbonylferrocene can occur obviously when deuterium substituted methanol is added, and the H / D exchange (EQ 4) can also occur smoothly without the addition of iodobenzene These results show that the activation of C-H bond is reversible and probably not a critical step Figure 3 summary of mechanism and control experiments (source: Nat Commun.) The research group of youshuli provided an efficient method for the synthesis of planar chiral ferrocene with thiocarbonyl group The reaction conditions were mild and the substrate was universal The reaction could be carried out well for the aryl iodides with different substituents and heterocyclic aryl iodides At present, the amount of catalyst for the reaction is still relatively high The author said that the reaction mechanism will be further studied in the future, and more efficient and mild catalytic system will be developed to realize the synthesis of planar chiral ferrocene compounds with various structures as well as valuable chiral ligands / catalysts Two types of catalysts are proposed.