Rigid backbone 1,8-anthracene-linked bis-oxazolines (AnBOXes): design, synthesis, application and characteristics in catalytic asymmetric aziridination

A series of rigid backbone 1,8-anthracene-linked bis-oxazolines (AnBOXes) have been designed, synthesized, and evaluated in the catalytic asymmetric aziridination with [N-(p-toluenesulfonyl)imino]phenyliodinane (PhINTs) as a nitrene source. The results indicate that highly enantioselective aziridination of chalcones catalyzed by an AnBOX and CuOTf complex with up to >99% ee and the opposite enantioselectivity, compared with the ligands of Evans et al., can be achieved. The enantioselectivity is substituent dependent with respect to chalcones. Chalcones with electron-donating substituents show higher enantioselectivities due to the stronger Lewis basicity of the oxygen of their carbonyl groups than those with electron-withdrawing substituents. The results also indicate that the coordination between the oxygen of the carbonyl group in chalcones and the ether group in alkenes with the copper in the catalyst is essential for high enantioselectivity, while the π–π stacking interaction between two reactants plays an importantly additional role for high enantioselectivity in asymmetric aziridination. An excellent backbone-controlled stereoselectivity was observed for the AnBOX ligands in asymmetric aziridination, as this will provide very important information for designing novel ligands.

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(S,S)-N,N′-Bis[1-(hydroxymethyl)-2-methylpropyl]-anthracene-1,8-dicarboxamideC26H32N2O4Ee = 100%[α]D24=-65.9 (c 0.41, CH3OH)Source of chirality: l-valinolAbsolute configuration: (S,S)

(S,S)-N,N′-Bis[1-(hydroxymethyl)-2-methylbutyl]-anthracene-1,8-dicarboxamideC28H36N2O4Ee = 100%[α]D24=-64.2 (c 0.53, CH3OH)Source of chirality: l-i-BuCHNH2CH2OHAbsolute configuration: (S,S)

(S,S)-N,N′-Bis[1-(hydroxymethyl)-2-phenylethyl]-anthracene-1,8-dicarboxamideC34H32N2O4Ee = 100%[α]D24=-21.2 (c 0.25, CH3OH)Source of chirality: l-BnCHNH2CH2OHAbsolute configuration: (S,S)

(S,S)-N,N′-Bis[1-(hydroxymethyl)-phenylmethyl]-anthracene-1,8-dicarboxamideC32H28N2O4Ee = 100%[α]D22=+31.8 (c 0.42, DMF)Source of chirality: l-PhCHNH2CH2OHAbsolute configuration: (S,S)

(S,S)-1,8-Bis[4-(1-methylethyl)oxazolin-2-yl]anthraceneC26H28N2O2Ee = 100%[α]D20=+64.7 (c 0.97, CHCl3)Source of chirality: l-valinolAbsolute configuration: (S,S)

(S,S)-1,8-Bis[4-(1-methylpropyl)oxazolin-2-yl]anthraceneC28H32N2O2Ee = 100%[α]D20=+17.9 (c 0.80, CHCl3)Source of chirality: l-i-BuNH2CH2OHAbsolute configuration: (S,S)

(S,S)-1,8-Bis[4-(1,1-dimethylethyl)oxazolin-2-yl]anthraceneC28H32N2O2Ee = 100%[α]D20=-10.9 (c 0.96, CHCl3)Source of chirality: l-t-BuNH2CH2OHAbsolute configuration: (S,S)

(S,S)-1,8-Bis[(4-benzyl)oxazolin-2-yl]anthraceneC34H28N2O2Ee = 100%[α]D20=+50.7 (c 0.92, CHCl3)Source of chirality: l-BnNH2CH2OHAbsolute configuration: (S,S)

(S,S)-1,8-bis[(4-phenyl)oxazolin-2-yl]anthraceneC34H24N2O2Ee = 100%[α]D20=+113 (c 0.56, CHCl3)Source of chirality: l-PhNH2CH2OHAbsolute configuration: (S,S)

(S,S)-N,N′-Bis[1-(hydroxymethyl)benzyl]-anthraquinone-1,8-dicarboxamideC34H30N2O6Ee = 100%[α]D24=-111.5 (c 0.85, CH3OH)Source of chirality: l-BnNH2CH2OHAbsolute configuration: (S,S)

(S,S)-1,8-Bis[(4-phenylmethyl)oxazolin-2-yl]anthraquinoneC34H26N2O4Ee = 100%[α]D20=-121 (c 0.51, acetone)Source of chirality: l-BnNH2CH2OHAbsolute configuration: (S,S)

(2S,3R)-2-Benzoyl-3-(4-phenylphenyl)-1-(4-toluenesulfonyl)aziridineC28H23NO3SEe = 87%[α]D20=+1.3 (c 0.64, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

(2S,3R)-2-Benzoyl-3-(4-fluorophenyl)-1-(4-toluenesulfonyl)aziridineC22H18FNO3SEe = 62%[α]D20=+1.7 (c 0.77, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

(2S,3R)-2-Benzoyl-3-(4-bromophenyl)-1-(4-toluenesulfonyl)aziridineC22H18BrNO3SEe = 52%[α]D20=+3.8 (c 1.02, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

(2S,3R)-2-Benzoyl-3-(4-methoxyphenyl)-1-(4-toluenesulfonyl)aziridineC23H21NO4SEe = 37%[α]D20=+23.8 (c 0.98, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

(2S,3R)-2-Benzoyl-3-(2-methoxyphenyl)-1-(4-toluenesulfonyl)aziridineC23H21NO4SEe = 27%[α]D20=-13.6 (c 0.45, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

(2S,3R)-2-(4-Fluorobenzoyl)-3-phenyl-1-(4-toluenesulfonyl)aziridineC22H18FNO3SEe = 54%[α]D25=+7.9 (c 0.68, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

(2S,3R)-2-(4-Chlorobenzoyl)-3-phenyl-1-(4-toluenesulfonyl)aziridineC22H18ClNO3SEe = 58%[α]D20=+10.6 (c 1.01, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

(2S,3R)-2-(4-Bromobenzoyl)-3-phenyl-1-(4-toluenesulfonyl)aziridineC22H18BrNO3SEe = 50%[α]D20=+10.8 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

(2S,3R)-2-(4-Nitrobenzoyl)-3-phenyl-1-(4-toluenesulfonyl)aziridineC22H18N2O5S[α]D20=+6.3 (c 0.73, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

(2S,3R)-2-(4-Methoxybenzoyl)-3-phenyl-1-(4-toluenesulfonyl)aziridineC23H21NO4SEe = 62%[α]D20=+3.4 (c 1.02, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

(2S,3R)-2-(4-Chlorobenzoyl)-3-(4-chlorophenyl)-1-(4-toluenesulfonyl)aziridineC22H17Cl2NO3SEe = 43%[α]D20=+9.25 (c 1.01, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

(2S,3R)-2-(4-Methylbenzoyl)-3-(4-chlorophenyl)-1-(4-toluenesulfonyl)aziridineC23H20ClNO3SEe = 39%[α]D20=+3.6 (c 1.04, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

(2S,3R)-2-Benzoyl-3-(4-trifluoromethylphenyl)-1-(4-toluenesulfonyl)aziridineC23H18F3NO3SEe = 67%[α]D20=+9.0 (c 0.55, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

(R,R)-2-Benzyl-3-phenyl-1-(4-toluenesulfonyl)aziridineC22H21NO2SEe = 6%[α]D20=-2.45 (c 1.06, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R)

(2S,3R)-2-Phenyl-3-phenoxylmethyl-1-(4-toluenesulfonyl)aziridineC22H21NO3SEe = 40%[α]D20=-10.8 (c 1.05, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

(2S,3R)-3-phenyl-1-(4-toluenesulfonyl)aziridin-2-ylmethyl tosylateC23H23NO5S2Ee = 27%[α]D20=-2.3 (c 0.27, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

(S,S)-2-(1-Phenoxy-phenylmethyl)-1-(4-toluenesulfonyl)aziridineC22H21NO3SEe = 19%[α]D20=+10.7 (c 0.45, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S)

(2S,3R)-2-Benzoyl-3-methyl-1-(4-toluenesulfonyl)aziridineC17H17NO3SEe = 9%[α]D20=-5.4 (c 0.21, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

(S,S)-1,3-Diphenoxy-1-phenyl-N-(4-toluenesulfonyl)propan-2-amineC28H27NO4SEe = 23%[α]D20=-5.8 (c 0.45, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S)