Novel tetradentate bisoxazoline ligands from l-serine and β-DDB for asymmetric pinacol coupling reactions of aromatic aldehydes

A variety of novel hydroxyl-containing tetradentate bisoxazolines were successfully synthesized from natural l-serine and β-DDB. The applications of these ligands in the asymmetric pinacol coupling of aromatic aldehydes revealed that the absolute configurations of the resulting pinacols were entirely dominated by the axial chirality of the biphenyl component and that the bulky substituent adjacent to the hydroxyl group was favorable for achieving both high diastereoselectivities and enantioselectivities. Among the ligands screened, (S,aR,S)-1c exhibited much better asymmetric induction capacity to furnish the (R,R)-pinacols with diastereoselectivities up to 99/1 and with 63–89% enantiomeric excess. A plausible mechanism of the asymmetric pinacol coupling was also suggested.

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(4S,4′S)-Dimethyl-2,2′-((S)-4,4′-dimethoxy-[5,5′-bibenzo[d][1,3]dioxole]-6,6′-diyl)bis(4,5-dihydro-oxazole-4-carboxylate)C26H24N2O12[α]D18=+30 (c 1, CHCl3)Absolute configuration: (4S,aS,4′S)Source of chirality: (S)-Dimethyl 4,4′-dimethoxy-[5,5′-bibenzo[d][1,3]dioxole]-6,6′-dicarboxylate, l-serine

((4R,4′R)-2,2′-((S)-4,4′-Dimethoxy-[5,5′-bibenzo[d][1,3]dioxole]-6,6′-diyl)bis(4,5-dihydrooxazole-4,2-diyl))dimethanolC24H24N2O10[α]D18=-54 (c 1, CHCl3)Absolute configuration: (4R,aS,4′R)Source of chirality: (S)-Dimethyl 4,4′-dimethoxy-[5,5′-bibenzo[d][1,3]dioxole]-6,6′-dicarboxylate, l-serine

3,3′-((4S,4′S)-2,2′-((S)-4,4′-Dimethoxy-[5,5′-bibenzo[d][1,3]dioxole]-6,6′-diyl)bis(4,5-dihydro oxazole-4,2-diyl))bis(pentan-3-ol)C32H40N2O10[α]D18=-37.4 (c 1, CHCl3)Absolute configuration: (4S,aS,4′S)Source of chirality: (S)-Dimethyl 4,4′-dimethoxy-[5,5′-bibenzo[d][1,3]dioxole]-6,6′-dicarboxylate, l-serine

((4S,4′S)-2,2′-((S)-4,4′-Dimethoxy-[5,5′-bibenzo[d][1,3]dioxole]-6,6′-diyl)bis(4,5-dihydrooxazole-4,2-diyl))bis(diphenylmethanol)C48H40N2O10[α]D18=-29 (c 1, CHCl3)Absolute configuration: (4S,aS,4′S)Source of chirality: (S)-Dimethyl 4,4′-dimethoxy-[5,5′-bibenzo[d][1,3]dioxole]-6,6′-dicarboxylate, l-serine