Cu-catalysed three-component C–H trifluoroalkylation of glycine derivatives: access to diverse CF₃-containing amino acids

Abstract

A Cu-catalysed method that selectively incorporates a trifluoromethyl group and an alkene moiety onto the α carbon of glycine derivatives has been developed using commercialized Togni II reagent. In this...

Cobalt(II)-Catalyzed Selective Three-Component Oxyalkylation of N-Aryl Glycinates: A Route to CF3-Labeled Threonine Analogues

“…Following the general procedure, compound 4fo was prepared through a reaction between 1f , tert -butyldimethyl­((2-methylallyl)­oxy)­silane 2o , and Togni II reagent 3a (7 h), and it was isolated through a silica gel flash column (PE/EtOAc = from 80:1 to 50:1) as a mixture of two diastereomers (colorless oil, 65.8 mg, 71% yield, dr 2.0:1). The characterization data of compound 4fo agree with our previous report …”

“…Besides, a cyclization product 6aa was generated in the FeCl 2 -mediated case, possibly via a Povarov-type mechanism . In our previous research, improved reactivity and selectivity were achieved by combining a metal salt and a N-based ligand. , Unfortunately, both the established Cu and Fe recipe favored the oxytrifluoromethylation of silyl vinyl ether, resulting in 5a as the only product (entries 3, 4). Next, a few photoredox catalysts were inspected under blue light irradiation.…”

“…CoCl 2 and Co(acac) 2 slightly favored the formation of glycine ligation product 4aa, and an aromatic substitution product 7a was detected in the former case (entries 7, 8). The optimum overall yield and selectivity were achieved with Co(OAc) (10), 1a as limiting reagent f 50°C 84 c trace a Unless otherwise stated, the reaction was carried out under N 2 with 1a (0.24 mmol), 2a (0.3 mmol), and 3a (0.2 mmol) in the presence of a metal salt (0.02 mmol) in anhydrous 1,2-dichloroethane (2 mL) at 50 °C (water bath) for 7 h. b Yield of 4aa, 5a, and 7a were determined by quantitative diastereomers were isolated for each case. It is reasonable to assign the two substituents on the ring to be opposite to each other.…”

“…The characterization data of compound 4fq agree with our previous report. 10 Gram-Scale Synthesis of Compound 4fa. To a 50 mL roundbottomed flask charged with a stir bar were added 1f (1.046 g, 5 mmol), 3a (1.90 g, 6 mmol), and Co(OAc) 2 (88.5 mg, 0.5 mmol).…”

“…The research in our lab has been focused on 3d metal-catalyzed radical modifications of glycine derivatives. Iron and copper were proven highly effective in converting a N -aryl glycinate into a corresponding imine, which then serves an excellent alkyl radical acceptor to achieve an overall redox-neutral C sp 3 –C sp 3 bond formation. Based on this, we envisage to develop a three-component radical addition cascade with a glycinate, a protected enol, and a trifluoromethylating reagent, which would provide a novel approach to diverse CF 3 -containing threonine analogues (Scheme D).…”