Copper-Catalyzed Asymmetric Borylation: Construction of a Stereogenic Carbon Center Bearing Both CF₃ and Organoboron Functional Groups

Abstract

Copper-catalyzed borylation of β-trifluoromethyl-α,β-unsaturated ketones was efficiently achieved by means of bis(pinacolato)diboron (Bpin), affording the enantioenriched products in good yields with high enantioselectivities. CuI and (R,S)-Josiphos consist of the most efficient catalyst system under mild conditions. In the absence of the chiral ligand, the reactions could be performed more efficiently to form β-ketone derivatives which were directly borylated and indirectly trifluoromethylated at the β-carbon atom of the α,β-unsaturated ketone substrates. The present protocol provides a promising method to access a stereogenic carbon center bearing both CF and organoboron functional groups.

Genetically programmed chiral organoborane synthesis

“…Chiral α-trifluoromethylated organoboranes are useful synthetic building blocks that combine the unique properties of fluorinated motifs with the versatile synthetic applications of organoboranes 35 ; however, methods for their asymmetric preparation are rare 11,36 . Our ability to biosynthesise both enantiomers of these molecules may have applications in pharmaceutical and agrochemical synthesis.…”

β‐Trifluoromethyl α,β‐unsaturated Ketones: Efficient Building Blocks for Diverse Trifluoromethylated Molecules

“…[68] To have both CF 3 and organoboron functionality on the stereogenic carbon center, Yu and coworkers in 2017 developed an efficient method for borylation of β-CF 3 enone with bis(pinacolato)diboron (B 2 pin 2 ) 112 in the presence of a catalyst CuI (5 mol%) and K 3 PO 4 (10 mol%) under nitrogen to afford the borylated product 113 with good yields. [69] The enantioselective borylated products were obtained by the additional use of chiral ligand (R,S-Josiphos) 116 in the reaction conditions. The enantioselectivity was found to be high (up to 95%) but the yields of the products 114 were up to 65% only due to the formation of difluoroborane side product 115 as shown in scheme 33.…”

A Biocatalytic Platform for Synthesis of Chiral α-Trifluoromethylated Organoborons

“…This class of organofluorine compounds serve as valuable synthetic building blocks that can be converted to a broad range of CF3-containing molecules via versatile boron-mediated transformations. [19][20][21][22][23][24] Despite the synthetic versatility of α-CF3 organoborons, their asymmetric preparation remains a challenge. The few known enantioselective examples in synthetic chemistry include a copper-catalyzed asymmetric hydroboration of CF3-substituted alkenes and enantioselective insertions of CF3-carbene intermediates into B-H bonds of Lewis-base borane complexes.…”

“…The few known enantioselective examples in synthetic chemistry include a copper-catalyzed asymmetric hydroboration of CF3-substituted alkenes and enantioselective insertions of CF3-carbene intermediates into B-H bonds of Lewis-base borane complexes. 21,25 The substrate scopes in both examples are very limited:…”

“…the hydroboration approach can only be applied to aromatic β-CF3-α,β-unsaturated ketones, 21 whereas the B-H insertion strategy has only been demonstrated with a few aryl substituted trifluorodiazo compounds. 25 The deficit of methods for making chiral α-CF3 organoborons motivated us to develop an enzymatic platform for their synthesis by reprogramming heme proteins to utilize trifluorodiazo alkanes for highly enantioselective carbene B-H bond insertion reactions (Figure 1a).…”