Recently，Liu& Tan joint research group sequentially published four papers in Angewandte Chemie International Editionin the field of functionalization of unactivated alkenes and enantioselective constructionof axially chiral compounds. It is worth noting that one of these papers has been highlighted as a back cover picture of Angewandte Chemie International Edition.
(“Brønsted Acid-Catalyzed Asymmetric Hydroamination of Alkenes: Synthesis of Pyrrolidines Bearing a Tetrasubstituted Carbon Stereocenter”, Angew. Chem. Int. Ed. 2015, 54, DOI:10.1002/anie.201501762). Chiral amines bearing an α-tetrasubstituted carbon stereocenter are important structural motifs in numerous biologically active compounds and potent pharmaceutical agents, which still remains a formidable synthetic challenge because of the difficulties associated with overcoming the steric hindrance and controlling the correct orientation of the four attached substituents. Liu & Tan joint group have successfully developed the first highly enantioselective Brønsted acidcatalyzed hydroamination of alkenes: synthesis of pyrrolidines bearing a tetrasubstituted carbon stereocenter with good to excellent yields and enantioselectivities undermild reaction conditions. A thiourea group that acts as both the activating and directing group is crucial for the hydroamination to proceed with high levels of stereoinduction by cooperative multiple hydrogen bonding with the Brønsted acid and the double bond. Furthermore, this transformation enables the efficient construction of spirocyclic pyrrolidines and tricyclic amines.
(“Enantioselective C-H Bond Functionalization Triggered by Radical Trifluoromethylation of Unactivated Alkene”, Angew. Chem., Int. Ed. 2014, 53, 11890-11894). Trifluoromethylated compounds have played a profound role in the realm of medicinal chemistry as ithas excellent metabolic stability, lipophilicity, and electrostaticinteractions with targets. Based on trifluoromethylation of unactivated alkene, Liu & Tan joint group have reported that an asymmetricunactivated alkene/C-H bond difunctionalization reaction for the concomitant construction of C-CF3 and C-O bonds was realized by using a Cu/Brønsted acid cooperative catalytic system,thus providing facile access to valuable chiral CF3-containing N,O-aminals with excellent regio-, chemo-, and enantioselectivity. The sustainable protocol provides a highly efficient method for the remote α-C-H asymmetric functionalization of amides. Due of this importance about this work, it has been highlighted by Prof. Lautens (Mark Lautens in University of Toronto) in Synfacts 2014, 10,1281.
(“Phosphine-Catalyzed Remote β-C-H Functionalization of Amine Triggered by Trifluoromethylation of Alkene: One-Pot Synthesis of Bistrifluoromethylated Enamides and Oxazoles”, Angew. Chem., Int. Ed. 2015, 54, 4041-4045). Based on their previous work, Liu & Tan joint group have disclosed an unprecedented phosphine-catalyzed remote β-Csp3-H functionalization of amide derivatives triggered by trifluoromethylation of an alkene with Togni’s reagent.This reaction proceeded through the highly selective and concomitant activation of an unactivated alkene and the β-Csp3-H bond of an aminederivative, providing bistrifluoromethylated enamides in excellent yields withgood regio-, chemo-, and stereoselectivity under mild and metal-free conditions.Furthermore, the newly developed one-pot protocol provides a facile and step-economicalaccess to valuable trisubstituted 5-(trifluoromethyl)oxazoles.This reaction is an advantageousalternative to the transition-metal-catalyzed β-Csp3-H bond functionalization of amine derivatives assisted by a nitrogen-based directing group.As the importance of this work, it has been selected as a back cover picture of this journal. In addition, relevant research works of remote α-C-H functionalization triggered by trifluoromethylation of alkenes with Togni’sreagent in their research group have been published in Chemistry-A European Journal (Chem.Eur. J. 2015, 21, 6718-6722), ACS Catal.( ACS Catal. 2015, 5,2826-2831), Organic Letters (Org. Lett. 2015, 17,1589-1592).
As the above systematic study of the remote α-C-H, β-Csp3-H functionalization of amide derivatives and α-C-H functionalization of carbonyl derivatives triggered by trifluoromethylation of an alkene with Togni’s reagent via1,5-H shift process, more recently, Prof. K. P. C. Vollhardt (Synlett editor) invited them to givea research account in Synlett.
(“Highly Enantioselective Kinetic Resolution of Axially Chiral BINAM Derivatives Catalyzed by a Brønsted Acid”, Angew. Chem., Int. Ed. 2014, 53, 3684-3687). The axially chiral BINAP, BINOL, and their derivatives are among the most successful chiral ligands/ catalysts in asymmetric catalysis, with extensive applications in various catalytic enantioselective transformations.As a result, the construction of these scaffolds has attracted considerable attention and the relatively practical methods have already been achieved. Liu & Tan joint group have developed a highly efficient strategy for the kinetic resolution of axially chiral BINAM derivatives involving a chiral Brønsted acid-catalyzed imine formation andtransfer hydrogenation cascade process. The kinetic resolution provides a convenient route to chiral BINAM derivatives in high yields with excellent enantioselectivities.This method features a general strategy by employing the well-known reactions for the kinetic resolution of structurally useful compounds with a high level of enantioselectivity. This work has also been highlighted by Prof. List (Benjamin List in Max-Planck-Institutfur Kohlenforschung) in Synfacts 2014, 10, 530.
Financial support from the National Natural Science Foundation of China, the National Basic Research Program of China, Shenzhen special funds for the development of biomedicine, Internet, newenergy, and new material industries is greatly appreciated.
