A practical synthesis of syn- and anti-α,β-dihydroxyphosphinates via diastereoselective reduction of α-phosphinoyl ketones

Reduction of β-keto-diphenylphosphine oxide (S)-4 derived from (S)-mandelic acid with NaBH4 in methanol at −78 °C gave the anti-3-diphenylphosphinoyl-1,2-diol 6, whereas the reduction of (S)-4 with Zn(BH4)2 in THF at −78 °C afforded the syn-1,2-diol 5, both in high yield and excellent diastereoselectivity. This procedure represents a new approach to the diastereoselective synthesis of diphenylphosphinoyl diols and an example of highly diastereoselective 1,2-induction. A theoretical model to explain the direction and degree of asymmetric induction is proposed.

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(S)-1-[(tert-Butyldimethylsilyl)oxy]-3-(diphenylphosphinoyl)-1-phenylpropan-2-oneC27H33O3PSiEe >98%[α]D = +20.9 (c 2.5, CHCl3)Source of chirality: (S)-mandelic acidAbsolute configuration: (S)

(1S,2R)-1-[(tert-Butyldimethylsilyl)oxy]-3-(diphenylphosphinoyl)-1-phenylpropan-2-olC27H35O3PSiEe >97%[α]D = +33.4 (c 2.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

(1S,2S)-1-[(tert-Butyldimethylsilyl)oxy]-3-(diphenylphosphinoyl)-1-phenylpropan-2-olC27H35O3PSiDe >97%[α]D = +49.7 (c 4.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S)

(1S,2R)-3-(Diphenylphosphinoyl)-1-phenylpropane-1,2-diolC21H21O3PDe >97%[α]D = −1.8 (c 0.7, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

(1S,2S)-3-(Diphenylphosphinoyl)-1-phenylpropane-1,2-diolC21H21O3PDe >97%[α]D = +45.7 (c 2.4, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S)

(4S,5R)-2,2-Dimethyl-4-phenyl-5-(diphenylphosphinoyl methyl)-1,3-dioxolaneC24H25O3PDe >98%[α]D = +5.5 (c 1.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4S,5R)

(4S,5S)-2,2-Dimethyl-4-phenyl-5-(diphenylphosphinoyl methyl)-1,3-dioxolaneC24H25O3PDe >98%[α]D = +66.6 (c 1.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4S,5S)