Electronic effects of aryl-substituted bis(oxazoline) ligands on the outcome of asymmetric copper-catalysed C–H insertion and aromatic addition reactions

The effect of the modification of bis(oxazoline) ligands on the outcome of copper-catalysed C–H insertion and aromatic addition reactions is described. In general, these reactions display minimum sensitivity in terms of enantiocontrol to variation of the electronic properties of the aryl moiety of the ligand however, some influence is observed for C–H insertions employing naphthyl-substituted bis(oxazolines) and for aromatic addition reactions of biphenyl diazo ketone substrates. The synthesis of the modified bis(oxazolines), which include four novel structures, is also described.

Figure optionsDownload as PowerPoint slide

2,2-Bis{2-[4(R)-(4-chlorophenyl)-1,3-oxazolinyl]}propaneC21H20Cl2N2O2[α]D20=+133.0 (c 0.37, CH2Cl2)Source of chirality: (R)-2-amino-2-(4-chlorophenyl)ethanolAbsolute configuration: (R)

2,2-Bis{2-[4(R)-(4-fluorophenyl)-1,3-oxazolinyl]}propaneC21H20F2N2O2Chiralcel OD-H; hexane/IPA; 98/2; 0.5 mL/min254 nm; tR(R) = 31 min; tR(S) = 34 min[α]D20=+125.7 (c 0.30, CHCl3)Source of chirality: (R)-2-amino-2-(4-fluorophenyl)ethanolAbsolute configuration: (R)

2,2-Bis{2-[4(R)-(4-methoxyphenyl)-1,3-oxazolinyl]}propaneC23H26N2O4[α]D25=+183.2 (c 0.50, CHCl3)Source of chirality: (R)-4-hydroxyglycineAbsolute configuration: (R)

2,2′-(Propane-2,2-diyl)bis[4-(4-chlorobenzyl)-4,5-dihydrooxazole]C23H24Cl2N2O2Chiralcel OD-H; hexane/IPA; 95/5; 1 mL/min;220 nm; tR(R) = 14 min; tR(S) = 32 min[α]D20=+53.5 (c 0.30, CHCl3)Source of chirality: (R)-2-amino-3-(4-chlorophenyl)propan-1-olAbsolute configuration: (R)

2,2′-(Propane-2,2-diyl)bis[4-(4-methoxybenzyl)-4,5-dihydrooxazole]C25H30N2O4Chiralcel OD-H; hexane/IPA; 95/5; 1 mL/min231 nm; tR(R) = 26 min; tR(S) = 40 min[α]D20=+25.7 (c 0.30, CHCl3)Source of chirality: (R)-2-amino-3-(4-methoxyphenyl)propan-1-olAbsolute configuration: (R)

2,2′-(Propane-2,2-diyl)bis[4-(4-naphthalene-2-ylmethyl)-4,5-dihydrooxazole]C31H30N2O2Chiralcel OD-H; hexane/IPA; 95/5; 1 mL/min218 nm; tR(R) = 27 min; tR(S) = 41 min[α]D20=+33.7 (c 0.30, CHCl3)Source of chirality: (R)-2-amino-3-(naphthalene-2-yl)propan-1-olAbsolute configuration: (R)