Lipase-catalyzed asymmetric acylation of boron cluster-containing secondary alcohols

The lipase-catalyzed asymmetric acetylation of secondary alcohols containing a carborane (boron cluster) moiety was investigated. Most lipases examined showed poor catalytic activity toward carborane-containing secondary alcohol 1a, but lipase TL efficiently catalyzed the acetylation of 1a with high enantioselectivity, to afford (R)-3a. This selectivity is similar to that of the general lipase-catalyzed acylation of secondary alcohols. Utilizing lipase TL, we succeeded in the resolution of carborane-containing alcohol 5, synthesized as a progesterone receptor ligand candidate, and evaluated the activities of the two enantiomers.

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(1S)-1-(7-Phenyl-1,7-dicarba-closo-dodecaboran-1-yl)ethanolC10H20B10Oee >99% (HPLC)[α]D25 = −12.3 (c 0.54, CH2Cl2)Source of chirality: lipase-catalyzed optical resolutionAbsolute configuration: (1S)

(2S)-1-(7-Phenyl-1,7-dicarba-closo-dodecaboran-1-yl)-2-propanolC11H22B10Oee >99% (HPLC)[α]D25 = +23.5 (c 0.3, CH2Cl2)Source of chirality: lipase-catalyzed optical resolutionAbsolute configuration: (1S)

(1R)-1-(7-Phenyl-1,7-dicarba-closo-dodecaboran-1-yl)ethyl acetateC12H22B10O2ee >99% (HPLC)[α]D25 = +68.0 (c 0.42, CH2Cl2)Source of chirality: lipase-catalyzed optical resolutionAbsolute configuration: (1R)

(1R)-1-(7-Phenyl-1,7-dicarba-closo-dodecaboran-1-yl)propan-1-yl acetateC13H24B10O2ee >99% (HPLC)[α]D25 = +52.9 (c 0.22, CH2Cl2)Source of chirality: lipase-catalyzed optical resolutionAbsolute configuration: (1R)

(1S)-1-(7-Phenyl-1,7-dicarba-closo-dodecaboran-1-yl)ethyl 2-((−)-10,2-camphorsultam-N-carbonyl)-4,5-dichlorobenzoateC28H37B10Cl2NO5See >99% (HPLC)[α]D25 = −82.1 (c 0.2, CH2Cl2)Source of chirality: lipase-catalyzed optical resolutionAbsolute configuration: (1S) (1S, 2R, 4R)

(1S)-1-(7-(4-Cyanophenyl)-1,7-dicarba-closo-dodecaboran-1-yl)ethanolC11H19B10NOee >99% (HPLC)[α]D25 = −10.8 (c 1.0, CH2Cl2)Source of chirality: lipase-catalyzed optical resolutionAbsolute configuration: (1S)