Lipase-catalyzed desymmetrization of meso-1,2-diaryl-1,2-diaminoethanes

The synthesis and enzyme-catalyzed desymmetrization of meso-1,2-diaryl-1,2-diaminoethanes have been investigated. A family of aromatic meso-1,2-diamines, containing different substitution patterns in the aromatic ring, was first prepared and then desymmetrized enantioselectively using lipases as biocatalysts. Selective alkoxycarbonylation of one of the amino groups was achieved using allyl carbonates, isolating the corresponding allyl monocarbamates with moderate to high enantiomeric excess at 45 °C. Candida antarctica lipase types A (CAL-A) and B (CAL-B) displayed the best activities and stereopreferences, with a dramatic influence being observed depending on the diamine structure. Non substituted and para-substituted aryldiamines led to the formation of allyl carbamates with good enantiomeric excess, using CAL-A for the less hindered substrates and CAL-B for the more hindered ones. On the other hand meta- and ortho-derivatives afforded low or negligible conversions and selectivities, respectively.

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Prop-2-en-1-yl[(1S,2R)-2-amino-1,2-diphenylethyl]carbamateC18H20N2O2Ee = 88% (HPLC, Column Chiralcel OJ-H)[α]D20=+1.0 (c 0.5, EtOH)Source of chirality: Lipase-catalyzed desymmetrization with CAL-AAbsolute configuration: (1S,2R)

Prop-2-en-1-yl[(1S,2R)-2-amino-1,2-bis(4-fluorophenyl)ethyl]carbamateC18H18F2N2O2Ee = 70% (HPLC, Column Chiralpak IC)[α]D20=+1.8 (c 0.5, EtOH)Source of chirality: Lipase-catalyzed desymmetrization with CAL-AAbsolute configuration: (1S,2R)

Prop-2-en-1-yl[(1S,2R)-2-amino-1,2-bis(4-chlorophenyl)ethyl]carbamateC18H18Cl2N2O2Ee = 88% (HPLC, Column Chiralcel OJ-H)[α]D20=+1.0 (c 0.5, EtOH)Source of chirality: Lipase-catalyzed desymmetrization with CAL-BAbsolute configuration: (1S,2R)

Prop-2-en-1-yl[(1S,2R)-2-amino-1,2-bis(4-bromophenyl)ethyl]carbamateC18H18Br2N2O2Ee = 91% (HPLC, Column Chiralpak IC)[α]D20=-2.9 (c 0.5, EtOH)Source of chirality: Lipase-catalyzed desymmetrization with CAL-BAbsolute configuration: (1S,2R)

Prop-2-en-1-yl[(1S,2R)-2-amino-1,2-bis(4-methylphenyl)ethyl]carbamateC20H24N2O2Ee = 80% (HPLC, Column Chiralpak IC)[α]D20=+7.6 (c 0.5, EtOH)Source of chirality: Lipase-catalyzed desymmetrization with CAL-AAbsolute configuration: (1S,2R)

Prop-2-en-1-yl[(1S,2R)-2-amino-1,2-bis(3-methylphenyl)ethyl]carbamateC20H24N2O2Ee = 18% (HPLC, Column Chiralpak IC)[α]D20=+3.8 (c 0.5, EtOH)Source of chirality: Lipase-catalyzed desymmetrization with CAL-AAbsolute configuration: (1S,2R)

Prop-2-en-1-yl[(1S,2R)-2-amino-1,2-bis(3-bromophenyl)ethyl]carbamateC18H18Br2N2O2Ee = 14% (HPLC, Column Chiralcel OJ-H)[α]D20=+1.2 (c 0.5, EtOH)Source of chirality: Lipase-catalyzed desymmetrization with CAL-AAbsolute configuration: (1S,2R)