Enantioselective rhodium-catalyzed hydrogenation of enol carbamates in the presence of monodentate phosphines

The rhodium-catalyzed asymmetric hydrogenation of different acyclic and cyclic enol carbamates to give optically active carbamates has been examined in the presence of chiral monodentate ligands based on a 4,5-dihydro-3H-dinaphthophosphepine motif 4. The enantioselectivity is largely dependent upon the reaction conditions, the nature of substituents on the phosphorus ligand and structure of the enol carbamate. By applying the optimized reaction conditions, enantioselectivities of up to 96% ee have been achieved.

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(S)-4-Phenyl-4,5-dihydro-3H-dinaphtho[2,1-c:1′,2′-e]phosphepine oxideC28H21OPEe = >98%[α]22 = +79 (c 0.46, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S,S,Sa)-3,5-Dimethyl-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c:1′,2′-e]phosphepine oxideC30H25OPEe = >98%[α]22 = +93.5 (c 0.25, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S,Sa)

(S,S,Sa)-3,5-Dimethyl-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c:1′,2′-e]phosphepineC30H25PEe = >98%[α]25 = +87.5 (c 0.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S,Sa)

(S)-4-(4-Methoxy)phenyl-4,5-dihydro-3H-dinaphtho[2,1-c:1′,2′-e]phosphepine oxideC29H23O2PEe = >98%[α]22 = −293 (c 0.25, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-1-Phenylethyl N,N-diethylcarbamateC13H19NO2Ee = 96%[α]23 = −146.1 (c 0.5, CH2Cl2/MeOH 1:1)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-1-Phenylethyl N,N-dimethylcarbamateC11H15NO2Ee = 75%[α]23 = −2.9 (c 0.3, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

1-Phenylethyl N-methyl N-phenylcarbamateC16H17NO2Ee = 65%[α]22 = +19.9 (c 0.26, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

1-Phenylethyl N,N-diphenylcarbamateC21H19NO2Ee = 76%[α]21 = −16.8 (c 0.33, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(S)-1-Phenylpropyl N,N-diethylcarbamateC14H21NO2Ee = 50%[α]23 = −143.7 (c 0.5, CH2Cl2/MeOH 1:1)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(+)-3,3-Dimethylbutan-2-yl diethylcarbamateC11H23NO2Ee = 67%[α]22 = +135 (c 0.04, CHCl3/MeOH)Source of chirality: asymmetric synthesis