Enantiomerically pure α-methoxyaryl acetaldehydes as versatile precursors: a facile chemo-enzymatic methodology for their preparation

A facile and efficient synthesis of optically active α-methoxyaryl acetic acids (up to 95% ee), α-methoxyaryl ethanols (up to 93% ee) and α-methoxyaryl acetonitriles (up to 93% ee) was achieved via Arthrobacter sp. lipase-catalyzed kinetic resolution of masked aldehydes as the key synthons, that is, α-hydroxyaryl acetaldehyde acetals.

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(S)-(+)-2,2-Dimethoxy-1-phenylethanolC10H14O3Ee = 99%[α]D25=+10.5 (c 1.0 CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(+)-2,2-Dimethoxy-1-(4-methoxyphenyl)ethanolC11H16O4Ee = 99%[α]D25=+14.5 (c 1.0 CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(+)-2,2-Dimethoxy-1-(3,4-dimethoxyphenyl)ethanolC12H18O5Ee = 99%[α]D25=+8.2 (c 1.0 CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(+)-2,2-Dimethoxy-1-(3,4-methylenedioxyphenyl)ethanolC11H14O5Ee = 99%[α]D25=+5.7 (c 1.0 CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(R)-(−)-Acetic acid-2,2-dimethoxy-1-phenylethylesterC12H16O4Ee = 99%[α]D25=-45.0 (c 0.5, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (R)

(R)-(−)-Acetic acid-2,2-dimethoxy-1-(4-methoxy phenyl)ethylesterC13H18O5Ee = 99%[α]D25=-61.0 (c 0.5, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (R)

(R)-(−)-Acetic acid-2,2-dimethoxy-1-(3,4-dimethoxyphenyl)ethylesterC13H16O6Ee = 99%[α]D25=-62 (c 1.0, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (R)

(R)-(−)-Acetic acid-2,2-dimethoxy-1-(3,4-dimethoxyphenyl)ethylesterC14H20O6Ee = 99%[α]D25=-52.2 (c 1.0, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (R)

(S)-(+)-1-(Phenyl)-1,2,2-trimethoxyethaneC11H16O3Ee = 95%[α]D25=+55.2 (c 1, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(+)-1-(4-Dimethoxyphenyl)-1,2,2-trimethoxyethaneC12H18O4Ee = 95%[α]D25=+52 (c 0.5, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(+)-1-(3,4-Dimethoxyphenyl)-1,2,2-trimethoxyethaneC13H20O5Ee = 95%[α]D25=+40.4 (c 1.0, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(+)-1-(3,4-Methylenedioxyphenyl)-1,2,2-trimethoxyethaneC12H16O5Ee = 95%[α]D25=+51 (c 1.0, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(+)-α-MethoxyphenylacetaldehydeC9H10O2[α]D25=+52 (c 0.5, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(+)-α-Methoxy-2-(4-methoxyphenyl)-acetaldehydeC10H12O3[α]D25=+68.1 (c 1.0, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(+)-α-Methoxy-2-(3,4-dimethoxyphenyl)acetaldehydeC11H14O4[α]D25=+54.5 (c 1.0, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(+)-α-Methoxy-2-(3,4-methylenedioxyphenyl)acetaldehydeC10H10O4[α]D25=+52.3 (c 1.0, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(+)-2-Methoxy-2-phenylethanolC9H12O2Ee >95%[α]D25=+104 (c 1.0, acetone)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(+)-2-Methoxy-2-(4-methoxyphenyl)ethanolC10H14O3Ee = 87%[α]D25=+92.4 (c 1.0, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(+)-2-Methoxy-2-(3,4-dimethoxyphenyl)ethanolC11H16O4Ee >93%[α]D25=+98 (c 0.5, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(+)-2-Methoxy-2-(3,4-methylenedioxyphenyl)ethanolC10H12O4Ee = 87%[α]D25=+87.5 (c 0.5, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(−)-2-Methoxy-2-phenylacetonitrileC9H7NOEe = 93%[α]D25=-67 (c 1.0, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(−)-2-Methoxy-2-(4-methoxyphenyl)acetonitrileC10H11NO2Ee = 89%[α]D25=-57 (c 1.0, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(−)-2-Methoxy-2-(3,4-dimethoxyphenyl)acetonitrileC11H13NO3Ee >93%[α]D25=-43 (c 1.0, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(−)-2-Methoxy-2-(3,4-methylenedioxyphenyl)acetonitrileC10H9NO3Ee = 89%[α]D25=-54.0 (c 1.0, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(+)-α-Methoxy-phenylaceticacidC9H10O3Ee = 80%[α]D25=+105 (c 0.5, EtOH)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(+)-α-Methoxy-2-(4-methoxyphenyl)aceticacidC10H12O4Ee = 90%[α]D25=+108 (c 0.5, EtOH)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(+)-2-Methoxy-2-(3,4-dimethoxyphenyl)acetic acidC11H14O5Ee = 91%[α]D25=+93.2 (c 0.5, EtOH)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)

(S)-(+)-α-Methoxy-2-(3,4-methylenedioxyphenyl)acetic acidC10H10O5Ee = 89%[α]D25=+106.0 (c 0.5, EtOH)Source of chirality: enzymatic hydrolysisAbsolute configuration: (S)