Asymmetric 1,4-addition of organoboronic acids to α,β-unsaturated ketones and 1,2-addition to aldehydes catalyzed by a palladium complex with a ferrocene-based phosphine ligand

A combination of palladium with ferrocene-based phosphine ligand with a carbon–bromine bond was found to be a good catalyst for the 1,4-addition of arylboronic acids to α,β-unsaturated ketones and the 1,2-addition to aldehydes. Using Pd(dba)2 and (S,Rp)-[1-(2-bromoferrocenyl)ethyl]diphenylphosphine (S,Rp)-1, 3-phenylcyclohexanone was obtained from the reaction of 2-cyclohexen-1-one with phenylboronic acid in the presence of K2CO3 in toluene at room temperature after 3 h in 92% yield with 76% ee. In the 1,2-addition of 4-methylphenylboronic acid to benzaldehyde, 96% of (4-methylphenyl)phenylmethanol was afforded after 24 h, while the enantiomeric excess was only 6%.

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(S)-3-PhenylcyclohexanoneC12H14OEe = 76%[α]D25=-17.2 (c 1.05, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-3-(4-Methyphenyl)cyclohexenoneC13H16OEe = 78%[α]D25=-12.0 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-3-(4-Methoxyphenyl)cyclohexenoneC13H16O2Ee = 76%[α]D25=-11.0 (c 1.05, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-3-(4-t-Butylphenyl)cyclohexanoneC16H22OEe = 79%[α]D25=-12.0 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-3-(4-Trifluoromethylphenyl)cyclohexanoneC13H13F3OEe = 4%[α]D25=-1.0 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-3-(4-Fluorophenyl)cyclohexanoneC12H13FOEe = 45%[α]D25=-17.7 (c 0.51, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-3-(1-Naphthyl)cyclohexanoneC16H16OEe = 42%[α]D25=-39.0 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-3-PhenylcyclopentanoneC11H12OEe = 54%[α]D25=-45.5 (c 1.01, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-3-PhenylcycloheptanoneC13H16OEe = 38%[α]D25=-28.2 (c 1.10, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-4-Phenyl-2-pentanoneC11H14OEe = 44%[α]D25=+14.0 (c 0.50, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-5-Phenyl-3-hexanoneC12H16OEe = 47%[α]D25=+26.0 (c 0.50, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-5-Methyl-4-phenyl-2-hexanoneC13H18OEe = 52%[α]D25=-16.0 (c 0.50, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-4-Phenyl-2-nonanoneC15H22OEe = 42%[α]D25=20.0 (c 0.50, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)