Zirconium–BINOLate-catalyzed, enantioselective aldol-Tishchenko reactions of aromatic ketone aldols

3,3′-Substituted BINOL’s have been identified as suitable chiral ligands for the zirconium-catalyzed aldol-Tishchenko reaction of aromatic ketone aldols with aliphatic aldehydes. 1,3-anti-Diol monoesters were obtained in excellent yields, complete anti-diastereocontrol, and enantioselectivities of up to 60% ee.

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(1S,3S)-1-Hydroxy-4-methyl-1-phenylpentan-3-yl isobutyrateC16H24O3Ee = 60%De >95%[α]D20=-5.7 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3S)

(1S,3S)-1-Cyclohexyl-3-hydroxy-3-phenylpropyl cyclohexanecarboxylateC22H32O3Ee = 54%De >95%[α]D20=-17.3 (c 1.1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3S)

(1S,3R)-1-Hydroxy-1-phenylnonan-3-yl heptanoateC22H36O3Ee = 41%De >95%[α]D20=-3.0 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R)

(1S,3R)-1-Hydroxy-5-methyl-1-phenylhexan-3-yl 4-methylpentanoateC19H30O3Ee = 42%De >95%[α]D20=-4.5 (c 1.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3R)

(1S,3S)-1-Hydroxy-4-methyl-1-p-tolylpentan-3-yl isobutyrateC17H26O3Ee = 50%De >95%[α]D20=-14.8 (c 1.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3S)

(1S,3S)-1-Cyclohexyl-3-hydroxy-3-p-tolylpropyl cyclohexanecarboxylateC23H34O3Ee = 56%De >95%[α]D20=-15.7 (c 1.1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3S)

(1S,3S)-1-Cyclohexyl-3-hydroxy-3-(4-methoxyphenyl)propyl cyclohexanecarboxylateC23H34O4Ee = 60%De >95%[α]D20=-9.3 (c 1.1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3S)

(1S,3S)-4-Ethyl-1-hydroxy-1-m-tolylhexan-3-yl 2-ethylbutanoateC21H34O3Ee = 49%De >95%[α]D20=-10.4 (c 1.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3S)

(1S,3S)-1-Cyclohexyl-3-hydroxy-3-m-tolylpropyl cyclohexanecarboxylateC23H34O3Ee = 53%De >95%[α]D20=-11.3 (c 1.1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,3S)