A study toward understanding the role of a phosphorus stereogenic center in (5S)-1,3-diaza-2-phospha-2-oxo-3-phenylbicyclo(3.3.0)octane derivatives as catalysts in the borane-mediated asymmetric reduction of prochiral ketones

Representative diastereomeric pairs of chiral catalysts, containing the (5S)-1,3-diaza-2-phospha-2-oxo-3-phenylbicyclo(3.3.0)octane moiety, with different stereochemistry at the phosphorus stereogenic center, have been synthesized and their stereoselection in the borane-mediated asymmetric reduction of representative prochiral ketones has been described.

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(2R,5S)-1,3-Diaza-2-phospha-2-oxo-2-chloro-3-phenylbicyclo(3.3.0)octaneC11H14N2OPCl[α]D25=-145.6 (c 1.04, CHCl3)Source of chirality: l-glutamic acidAbsolute configuration: 2R,5S

(2S,5S)-1,3-Diaza-2-phospha-2-oxo-2,3-diphenylbicyclo(3.3.0)octaneC17H19N2OP[α]D25=-31.4 (c 1.02, CHCl3)Source of chirality: l-glutamic acidAbsolute configuration: 2S,5S

(2R,5S)-1,3-Diaza-2-phospha-2-oxo-2,3-diphenylbicyclo(3.3.0)octaneC17H19N2OP[α]D25=+107.6 (c 0.98, CHCl3)Source of chirality: l-glutamic acidAbsolute configuration: 2R,5S

(2S,5S)-1,3-Diaza-2-phospha-2-oxo-2-piperidinyl-3-phenylbicyclo(3.3.0)octaneC16H24N3OP[α]D25=-21.2 (c 0.84, CHCl3)Source of chirality: l-glutamic acidAbsolute configuration: 2S,5S

(2R,5S)-1,3-Diaza-2-phospha-2-oxo-2-piperidinyl-3-phenylbicyclo(3.3.0)octaneC16H24N3OP[α]D25=+64.9 (c 1.55, CHCl3)Source of chirality: l-glutamic acidAbsolute configuration: 2R,5S

(R)-1-PhenylethanolC8H10OEe = 65%[α]D25=+29.2 (c0.99, MeOH)Source of chirality: asymmetric reductionAbsolute configuration: R

(S)-2-Chloro-1-phenylethanolC8H9OClEe = 76%[α]D25=+38.5 (c 1.01, cyclohexane)Source of chirality: asymmetric reductionAbsolute configuration: S

(S)-2-Bromo-1-phenylethanolC8H9OBrEe = 83%[α]D25=+36.1 (c 1.02, CHCl3)Source of chirality: asymmetric reductionAbsolute configuration: S