Iron-Catalyzed Asymmetric Haloazidation of α,β-Unsaturated Ketones: Construction of Organic Azides with Two Vicinal Stereocenters

Abstract

Organic azides play important roles in synthetic chemistry, chemical biology, drug discovery, and material science. Azido-functionalization of alkenes is one of the most efficient procedures for rapid introduction of azide group into organic compounds. But only a few examples have been documented in the catalytic asymmetric version of the azidation of alkenes. Herein, we report an unprecedented highly diastereo- and enantioselective bromoazidation of α,β-unsaturated ketones catalyzed by chiral N,N'-dioxide/Fe(OTf) complexes. An array of aryl, heteroaryl, and alkyl substituted α,β-unsaturated ketones were transformed to the corresponding α-bromo-β-azido ketones in high yields with excellent diastereo- and enantioselectivities. The catalytic system was also applicable for chloroazidation and iodoazidation of chalcone. Kinetic studies and some control experiments suggested that the reaction might proceed via a 1,4-addition/halogenation pathway.

Hypervalent Iodine(III)‐Promoted Rapid Cascade Reaction of Quinoxalinones with Unactivated Alkenes and TMSN3

“…Initially, target product (4 a) was obtained in 84% yield within 1 h by using 2.0 equivalents of PhI (TFA) 2 and 1.0 mL of MeCN at room temperature ( Table 1, entry 1). Other oxidants, such as PhI(OAc) 2 , K 2 S 2 O 8 and TBHP did not enhance the product yield ( Table 1, entries [2][3][4][5]. Subsequently, some organic solvents including dichloromethane (DCM), dichloroethane (DCE), toluene, tetrahydrofuran (THF), dimethyl formamide (DMF) and dimethylsulfoxide (DMSO) were explored (Table 1, entries 1,[6][7][8][9][10][11], and found that dichloromethane (DCM) was the optimal solvent for this transformation.…”

Recent developments in enantioselective iron-catalyzed transformations

“…Scheme 31. Chloroazidation and iodoazidation of chalcone [64]. enantioselectivity (95% ee) albeit combined with moderate antidiastereoselectivity (42% de).…”

“…Intramolecular chloroetherification and bromoetherification of activated alkenes [63]. catalyzed bromoazidation of a,b-unsaturated ketones 67 [64]. The catalyst was in situ generated from 0.5 mol% of Fe(OTf) 2 and ligand 66 in dichloroethane at 0°C.…”

“…It represented the first highly diastereo-and enantioselective iron-catalyzed haloazidation of a, b-unsaturated ketones. The same catalytic system was also applicable to the chloroazidation and iodoazidation of chalcone 33, as depicted in Scheme 31 [64]. The reactions required higher catalyst loadings of 5 mol% and 2.5 mol%, respectively.…”

“…The chloroazidation of chalcone with p-NsCl 2 as a chloride source and TMSN 3 as an azidation agent led to the corresponding chiral product 69 in good yield (69%) and high Scheme 30. Bromoazidation of a,b-unsaturated ketones [64].…”