Lipase-mediated stereoselective transformations of chiral organophosphorus P-boranes revisited: revision of the absolute configuration of alkoxy(hydroxymethyl)phenylphosphine P-boranes

The lipase-promoted kinetic resolution of a series of alkoxy(hydroxymethyl)phenylphosphine P-boranes proceeded with moderate stereoselectivity to give both the unreacted substrates and their O-acetyl derivatives. The absolute configurations of the products, which were earlier ascribed on the basis of the stereoselective reduction of the corresponding phosphine oxides with borane and comparison with the literature data concerning bicyclic phosphine oxides, were disputed by theoretical calculation. Some additional studies were carried out, including theoretical calculations and more accurate chemical correlation, which proved that the borane reduction of acyclic phosphine oxides proceeded with inversion of configuration at the phosphorus center and, therefore, the former assignment of the absolute configurations was incorrect. On this basis, the stereochemistry of the enzymatic reaction was ultimately determined. A mechanism of the borane reduction of acyclic phosphine oxides explaining inversion of configuration at phosphorus is proposed.

Figure optionsDownload as PowerPoint slide

Hydroxymethyl(isopropoxy)phenylphosphine oxideC10H15O3PEe = 100%[α]D = +58.3 (c 1, MeOH)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: (S) (literature data)

Isopropoxy(phenyl)tosyloxymethylphosphineC17H21O5PSEe = 100%[α]D = −6.4 (c 1.46, CHCl3)Source of chirality: stereospecific transformationAbsolute configuration: (S) (chemical correlation)

Iodomethyl(isopropoxy)phenylphosphine oxideC10H14IO2PEe = 100%[α]D = +26.2 (c 1.12, CHCl3)Source of chirality: stereospecific transformationAbsolute configuration: (S) (chemical correlation)

Isopropoxy(methyl)phenylphosphine oxideC10H15O2PEe = 100%[α]D = +40.0 (c 1.06, CHCl3)Source of chirality: stereospecific transformationAbsolute configuration: (R) (chemical correlation)

Isopropoxy(methyl)phenylphosphine sulfideC10H15OPSEe = 100%[α]D = −25.2 (c 1, CHCl3)Source of chirality: stereospecific transformationAbsolute configuration: (R) (chemical correlation)

Isopropoxy(methyl)phenylphosphine P-boraneC10H18BOPEe = 100%[α]D = +68.4 (c 2.25, CHCl3)Source of chirality: stereospecific transformationAbsolute configuration: (S) (chemical correlation)

t-Butyl(hydroxymethyl)phenylphosphine sulfideC11H18OPSEe = 45%[α]D = −5.7 (c 1.02, CHCl3)Source of chirality: stereospecific transformationAbsolute configuration: (R) (chemical correlation)

Acetoxymethyl(t-butyl)phenylphosphine sulfideC13H19O2PSEe = 45%[α]D = + 27.8 (c 1.02, CHCl3)Source of chirality: stereospecific transformationAbsolute configuration: (S) (chemical correlation)

Acetoxymethyl(t-butyl)phenylphosphine oxideC13H19O3PEe = 45%[α]D = +13.2 (c 1, CHCl3)Source of chirality: stereospecific transformationAbsolute configuration: (S) (chemical correlation)

t-Butyl(hydroxymethyl)phenylphosphine P-boraneC11H20BOPEe = 45%[α]D = +3.9 (c 1, CHCl3)Source of chirality: stereospecific transformationAbsolute configuration: (S) (chemical correlation)

t-Butyl(hydroxymethyl)phenylphosphine oxideC11H17O2PEe = 45%[α]D = −4.8 (c 1, CHCl3)Source of chirality: stereospecific transformationAbsolute configuration: (S) (literature data)

Hydroxymethyl(methoxy)phenylphosphine P-boraneC8H14BO2PEe = 100%[α]D = +80.2 (c 1, CHCl3)Source of chirality: stereospecific transformationAbsolute configuration: (S) (chemical correlation)

Hydroxymethyl(isopropoxy)phenylphosphine P-boraneC10H18BO2PEe = 100%[α]D = +101 (c 1.15, CHCl3)Source of chirality: stereospecific transformationAbsolute configuration: (S) (chemical correlation, theoretical calculations)

Hydroxymethyl(isopropoxy)phenylphosphine sulfideC10H15O2PSEe = 100%[α]D = +26.1 (c 1.57, CHCl3)Source of chirality: stereospecific transformationAbsolute configuration: (R) (chemical correlation)

Hydroxymethyl(methoxy)phenylphosphine sulfideC8H12O2PSEe = 100%[α]D = +23.4 (c 1.17, CHCl3)Source of chirality: stereospecific transformationAbsolute configuration: (R) (chemical correlation)

Acetoxymethyl(methoxy)phenylphosphine oxideC10H13O3PEe = 85%[α]D = −45.2 (c 1.17, CHCl3)Source of chirality: stereospecific transformationAbsolute configuration: (R) (chemical correlation)

Acetoxymethyl(isopropoxy)phenylphosphine oxideC13H19O3PEe = 79%[α]D = −30.5 (c 1.17, CHCl3)Source of chirality: stereospecific transformationAbsolute configuration: (R) (chemical correlation)

Acetoxymethyl(isopropoxy)phenylphosphine sulfideC12H17O2PSEe = 79%[α]D = −18.2 (c 1.1, CHCl3)Source of chirality: stereospecific transformationAbsolute configuration: (S) (chemical correlation)

Acetoxymethyl(methoxy)phenylphosphine sulfideC8H13O2PSEe = 85%[α]D = −31.4 (c 1.1, CHCl3)Source of chirality: stereospecific transformationAbsolute configuration: (S) (chemical correlation)