Synthesis of non-symmetric bisoxazoline compounds. An easy way to reach tailored chiral ligands

Bisoxazoline compounds have been used as chiral catalyst ligands in a wide variety of reactions. A great deal of effort has been aimed at the synthesis of C2-symmetric bisoxazolines but very few references exist for non-symmetric ones. As part of our studies into the possible usefulness of non-symmetric bisoxazolines, we report an easy method for the synthesis of bisoxazoline compounds bearing different substituents in each oxazoline ring.

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(4S)-4-tert-Butyl-2-[1-(4,5-dihydro-1,3-oxazol-2-yl)-1-methylethyl]-4,5-dihydro-1,3-oxazoleC13H22N2O2[α]D = −44.6 (c 1, CH2Cl2)Source of chirality: (S)-2-amino-3,3-dimethyl-1-butanol

(4S)-2-[1-(4,5-Dihydro-1,3-oxazol-2-yl)-1-methylethyl]-4-methyl-4-phenyl-4,5-dihydro-1,3-oxazoleC16H20N2O2[α]D = +4.6 (c 1, EtOH)Source of chirality: (S)-2-amino-2-phenylpropan-1-ol

(4S)-2-[1-(4,5-Dihydro-1,3-oxazol-2-yl)-1-methylethyl]-4-phenyl-4,5-dihydro-1,3-oxazoleC15H18N2O2[α]D = −124.6 (c 1, CH2Cl2)Source of chirality: (S)-2-amino-2-phenylethanol

(3aS,8aR)-2-[1-(4,5-Dihydro-1,3-oxazol-2-yl)-1-methylethyl]-8,8a-dihydro-3aH-indeno[1,2-d][1,3]oxazoleC16H18N2O2[α]D = −206.3 (c 1, EtOH)Source of chirality: (1S,2R)-(−)-cis-1-amino-2-indanol

(4S)-4-tert-Butyl-2-{1-methyl-1-[(4S)-4-phenyl-4,5-dihydro-1,3-oxazol-2-yl]ethyl}-4,5-dihydro-1,3-oxazoleC19H26N2O2[α]D = −173.3 (c 1, CH2Cl2)Source of chirality: (S)-2-amino-3,3-dimethyl-1-butanol(S)-2-amino-2-phenylethanol

(4S)-4-tert-Butyl-2-{1-methyl-1-[(4S)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]ethyl}-4,5-dihydro-1,3-oxazoleC14H24N2O2[α]D = −86.9 (c 0.8, CH2Cl2)Source of chirality: (S)-2-amino-3,3-dimethyl-1-butanol(S)-2-aminopropan-1-ol

(4S)-4-Benzyl-2-{1-[(4S)-4-tert-Butyl-4,5-dihydro-1,3-oxazol-2-yl]-1-methylethyl}-4,5-dihydro-1,3-oxazoleC20H28N2O2[α]D = −91.1 (c 1, CH2Cl2)Source of chirality: (S)-2-amino-3,3-dimethyl-1-butanol(S)-2-amino-3-phenylpropan-1-ol

(4S)-4-[(Benzyloxy)methyl]-2-{1-[(4S)-4-tert-Butyl-4,5-dihydro-1,3-oxazol-2-yl]-1-methylethyl}-4,5-dihydro-1,3-oxazoleC21H30N2O3[α]D = −96.9 (c 1, CH2Cl2)Source of chirality: (S)-2-amino-3,3-dimethyl-1-butanol(R)-2-amino-3-(benzyloxy)propan-1-ol