Synthesis of aryl(ferrocenyl)methanols via an enantioselective addition of arylboronic acids

Enantiomerically enriched ferrocenyl alcohols are important intermediates in the synthesis of a range of chiral ferrocene-derived ligands. We studied various possibilities for their synthesis by the catalytic enantioselective addition of arylboronic acids to ferrocenyl carbonyl compounds. The best system comprised of ferrocenyl oxazolinyl alcohol as a catalyst and an arylation reagent generated from a boronic acid and diethylzinc. Aryl ferrocenyl methanols were synthesized in yields of up to 97% and with enantiomeric purities of up to er 98:2.

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(R)-Ferrocenyl(phenyl)methanolC17H15ClFeOEr = 93:7 (by HPLC on chiral column)[α]D20=-14.8 (c 0.5, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Ferrocenyl(4-methoxyphenyl)methanolC18H18FeOEr = 60:40 (by HPLC on chiral column)[α]D20=-12.8 (c 0.76, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Ferrocenyl(2-methoxyphenyl)methanolC18H18FeOEr = 69:31 (by HPLC on chiral column)[α]D20=-20.6 (c 0.56, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Ferrocenyl(4-fluorophenyl)methanolC17H15FFeOEr = 74:24 (by HPLC on chiral column)[α]D20=-12.4 (c 1.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Ferrocenyl(4-chlorophenyl)methanolC17H15FFeOEr = 80:20 (by HPLC on chiral column)[α]D20=-17.9 (c 1.01, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Ferrocenyl(4-bromorophenyl)methanolC17H15BrFeOEr = 82:18 (by HPLC on chiral column)[α]D20=-35.4 (c 0.46, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Ferrocenyl(3-bromorophenyl)methanolC17H15BrFeOEr = 80:20 (by HPLC on chiral column)[α]D20=-13.5 (c 1.5, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Ferrocenyl(2-bromorophenyl)methanolC17H15BrFeOEr = 77:23 (by HPLC on chiral column)[α]D20=-16.3 (c 1.2, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Ferrocenyl(4-iodophenyl)methanolC17H15IFeOEr = 87:13 (by HPLC on chiral column)[α]D20=-15.1 (c 1.4, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-4-Cyanophenyl(ferrocenyl)methanolC18H15FeNOEr = 71:29 (by HPLC on chiral column)[α]D20=-11.9 (c 1.3, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Naphthyl(ferrocenyl)methanolC21H18FeOEr = 83:17 (by HPLC on chiral column)[α]D20=-31.2 (c 0.6, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-2-Furyl(ferrocenyl)methanolC15H14FeO2Er = 56:44 (by HPLC on chiral column)[α]D20=-18.4 (c 1.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R,R)-1,1′-Bis(α-hydroxyphenylmethyl)ferroceneC24H22FeO2Er = 97:3 (by HPLC on chiral column)[α]D20=-34.8 (c 0.91, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R)

(R,R)-1,1′-Bis(α-hydroxy-4-chlorophenylmethyl)ferroceneC24H20Cl2FeO2Er = 85:15 (by HPLC on chiral column)[α]D20=-25.3 (c 0.71, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R)

(R,R)-1,1′-Bis(α-hydroxy-4-bromophenylmethyl)ferroceneC24H20Br2FeO2Er = 85:15 (by HPLC on chiral column)[α]D20=-30.2 (c 1.6, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R)

(R,R)-1,1′-Bis(α-hydroxy-2-bromophenylmethyl)ferroceneC24H20Br2FeO2Er = 79:21 (by HPLC on chiral column)[α]D20=-10.4 (c 0.9, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R)