Enantioselective synthesis of optically active alkylphosphonates via Rh-catalyzed asymmetric hydrogenation of β-substituted α,β-unsaturated phosphonates

The Rh-catalyzed asymmetric hydrogenation of β-substituted α,β-unsaturated phosphonates using (Sc,Sp)-WalPhos as the chiral ligand is reported, in which a wide range of optically active β-substituted alkylphosphonates were obtained in good yields and with good to excellent enantioselectivities (86–98% ee). In contrast to the Rh/(Rc,Sa)-FAPhos system previously reported by us, the present catalytic system shows a wider substrate scope, and can perform the hydrogenation under milder reaction conditions.

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Diethyl 2-phenylpropylphosphonateC13H21O3PEe = 93%[α]D25=+17.85 (c 0.82, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: (R)

Diethyl 2-(2-methoxyphenyl)propylphosphonateC14H23O4PEe = 87%[α]D25=+5.7 (c 0.88, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: unknown

Diethyl 2-(3-methoxyphenyl)propylphosphonateC14H23O4PEe = 94%[α]D25=+19.3 (c 0.92, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: unknown

Diethyl 2-(4-methoxyphenyl)propylphosphonateC14H23O4PEe = 94%[α]D25=+21.7 (c 0.84, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: unknown

Diethyl 2-o-tolylpropylphosphonateC14H23O3PEe = 86%[α]D25=+11.9 (c 0.76, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: unknown

Diethyl 2-m-tolylpropylphosphonateC14H23O3PEe = 94%[α]D25=+18.5 (c 0.92, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: unknown

Diethyl 2-p-tolylpropylphosphonateC14H23O3PEe = 94%[α]D25=+22.15 (c 0.74, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: unknown

Diethyl 2-(3-(trifluoromethyl)phenyl)propylphosphonateC14H20F3O3PEe = 92%[α]D25=+18.7 (c 0.92, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: unknown

Diethyl 2-(4-(trifluoromethyl)phenyl)propylphosphonateC14H20F3O3PEe = 93%[α]D25=+18.2 (c 0.92, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: unknown

Diethyl 2-(4-fluorophenyl)propylphosphonateC13H20FO3PEe = 94%[α]D25=+17.3 (c 0.78, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: unknown

Diethyl 2-(4-chlorophenyl)propylphosphonateC13H20ClO3PEe = 94%[α]D25=+23.4 (c 0.92, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: unknown

Diethyl 2-(4-bromophenyl)propylphosphonateC13H20BrO3PEe = 95%[α]D25=+22.7 (c 1.06, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: unknown

Diethyl 2-(naphthalen-2-yl)propylphosphonateC17H23O3PEe = 91%[α]D25=+24.2 (c 1.04, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: unknown

Diethyl 2-(thiophen-2-yl)propylphosphonateC11H19O3PSEe = 98%[α]D25=+18.6 (c 0.60, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: unknown

Diethyl 2-methyl-4-phenylbutylphosphonateC15H25O3PEe = 96%[α]D25=+12.3 (c 0.86, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: unknown

Diethyl 2-phenylbutylphosphonateC14H23O3PEe = 93%[α]D25=+10.0 (c 1.14, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: unknown

Diethyl 2-(4-methoxyphenyl)butylphosphonateC15H25O4PEe = 94%[α]D25=+10.45 (c 1.18, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: unknown

Diethyl 2-phenylpentylphosphonateC15H25O3PEe = 93%[α]D25=+7.9 (c 1.22, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: unknown

Diethyl (1,2,3,4-tetrahydronaphthalen-1-yl)methylphosphonateC15H23O3PEe = 93%[α]D25=-3.5 (c 0.94, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: unknown