Efficient alcoholysis of 5,6-dihydro-1,10-phenanthroline-5,6-epoxide with ytterbium(III) triflate and subsequent enantioselective transesterification with lipases

New 5,6-dihydro-1,10-phenanthroline derivatives were prepared in high yield via ytterbium(III) triflate-catalyzed alcoholysis of the corresponding epoxide. Enzymatic transesterifications of racemic alkoxy alcohols afforded enantioselective separations with up to 99% ee. The lipase derived from Burkholderia cepacia (PSCI) was the most efficient, with E-values of up to 200. The steric effect of substituents in the 6-position on reaction time and enantioselectivities was assessed.

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(S,S)-5,6-Dihydro-6-methoxy-1,10-phenanthrolin-5-ol ((S,S)-5,6-dihydro-5-hydroxy-6-methoxy-1,10-phenanthroline)C13H12N2O2Ee = 99%[α]D25=+108.4 (c 0.43, CH3OH)Source of chirality: lipase-catalyzed resolutionAbsolute configuration: (5S,6S)

(S,S)-5,6-Dihydro-6-ethoxy-1,10-phenanthrolin-5-ol ((S,S)-5,6-dihydro-6-ethoxy-5-hydroxy-1,10-phenanthroline)C14H14N2O2Ee = 99%[α]D25=+75.2 (c 1, CH3OH)Source of chirality: lipase-catalyzed resolutionAbsolute configuration: (5S,6S)

(S,S)-5,6-Dihydro-6-propoxy-1,10-phenanthrolin-5-ol ((S,S)-5,6-dihydro-5-hydroxy-6-propoxy-1,10-phenanthroline)C15H16N2O2Ee = 96%[α]D25=+96.9 (c 1, CH3OH)Source of chirality: lipase-catalyzed resolutionAbsolute configuration: (5S,6S)

(S,S)-5,6-Dihydro-6-isopropoxy-1,10-phenanthrolin-5-ol ((S,S)-5,6-dihydro-5-hydroxy-6-isopropoxy-1,10-phenanthroline)C15H16N2O2Ee = 86%[α]D25=+43.4 (c 1, CH3OH)Source of chirality: lipase-catalyzed resolutionAbsolute configuration: (5S,6S)

(S,S)-5,6-Dihydro-6-butoxy-1,10-phenanthrolin-5-ol, ((S,S)-5,6-dihydro-6-butoxy-5-hydroxy-1,10-phenanthroline)C16H18N2O2Ee = 96%[α]D25=+100.9 (c 1, CH3OH)Source of chirality: lipase-catalyzed resolutionAbsolute configuration: (5S,6S)

(S,S)-5,6-Dihydro-6-allyloxy-1,10-phenanthrolin-5-ol ((S,S)-5,6-dihydro-6-allyloxy-5-hydroxy-1,10-phenanthroline)C15H14N2O2Ee = 96%[α]D25=+103.3 (c 1, CH3OH)Source of chirality: lipase-catalyzed resolutionAbsolute configuration: (5S,6S)

(S,S)-5,6-Dihydro-6-benzyloxy-1,10-phenanthrolin-5-ol ((S,S)-5,6-dihydro-6-benzyloxy-5-hydroxy-1,10-phenanthroline)C19H16N2O2Ee = 90%[α]D25=+95.9 (c 1, CH3OH)Source of chirality: lipase-catalyzed resolutionAbsolute configuration: (5S,6S)

(S,S)-5,6-Dihydro-6-cyclohexyloxy-1,10-phenanthrolin-5-ol ((S,S)-5,6-dihydro-6-cyclohexyloxy-5-hydroxy-1,10-phenanthroline)C18H20N2O2Ee = 80%[α]D25=+43.9 (c 1, CH3OH)Source of chirality: lipase-catalyzed resolutionAbsolute configuration: (5S,6S)

(R,R)-5,6-Dihydro-6-methoxy-1,10-phenanthrolin-5-yl acetate ((R,R)-5,6-dihydro-5-acetoxy-6-methoxy-1,10-phenanthroline)C15H14N2O3Ee = 96%[α]D25=-303.4 (c 0.4, CH3OH)Source of chirality: lipase-catalyzed resolutionAbsolute configuration: (5R,6R)

(R,R)-5,6-Dihydro-6-ethoxy-1,10-phenanthrolin-5-yl acetate ((R,R)-5,6-dihydro-5-acetoxy-6-ethoxy-1,10-phenanthroline)C16H16N2O3Ee = 98%[α]D25=-293.6 (c 1, CH3OH)Source of chirality: lipase-catalyzed resolutionAbsolute configuration: (5R,6R)

(R,R)-5,6-Dihydro-6-propoxy-1,10-phenanthrolin-5-yl acetate ((R,R)-5,6-dihydro-5-acetoxy-6-propoxy-1,10-phenanthroline)C17H18N2O3Ee = 98%[α]D25=-292.1 (c 1, CH3OH)Source of chirality: lipase-catalyzed resolutionAbsolute configuration: (5R,6R)

(R,R)-5,6-Dihydro-6-isopropoxy-1,10-phenanthrolin-5-yl acetate ((R,R)-5,6-dihydro-5-acetoxy-6-isopropoxy-1,10-phenanthroline)C17H18N2O3Ee = 94%[α]D25=-185.8 (c 1, CH3OH)Source of chirality: lipase-catalyzed resolutionAbsolute configuration: (5R,6R)

(R,R)-5,6-Dihydro-6-butoxy-1,10-phenanthrolin-5-yl acetate ((R,R)-5,6-dihydro-5-acetoxy-6-butoxy-1,10-phenanthroline)C18H20N2O3Ee = 98%[α]D25=-240.5 (c 1, CH3OH)Source of chirality: lipase-catalyzed resolutionAbsolute configuration: (5R,6R)

(R,R)-5,6-Dihydro-6-allyloxy-1,10-phenanthrolin-5-yl acetate ((R,R)-5,6-dihydro-5-acetoxy-6-allyloxy-1,10-phenanthroline)C17H16N2O3Ee = 98%[α]D25=-290.8 (c 1, CH3OH)Source of chirality: lipase-catalyzed resolutionAbsolute configuration: (5R,6R)

(R,R)-5,6-Dihydro-6-benzyloxy-1,10-phenanthrolin-5-yl acetate ((R,R)-5,6-dihydro-5-acetoxy-6-benzyloxy-1,10-phenanthroline)C21H18N2O3Ee = 96%[α]D25=-280.8 (c 1, CH3OH)Source of chirality: lipase-catalyzed resolutionAbsolute configuration: (5R,6R)

(R,R)-5,6-Dihydro-6-cyclohexyloxy-1,10-phenanthrolin-5-yl acetate ((R,R)-5,6-dihydro-5-acetoxy-6-cyclohexyloxy-1,10-phenanthroline)C20H22N2O3Ee = 91%[α]D25=-156.5 (c 1, CH3OH)Source of chirality: lipase-catalyzed resolutionAbsolute configuration: (5R,6R)