β-Hydroxy and β-(o-diphosphino)benzoyloxy(o-diphosphino) benzamides as ligands for asymmetric allylic alkylation

Diphenylphosphinobenzoic acid was treated with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), DMAP, and with either one of two equivalents of (1R,2S)-norephedrine and (1S,2S)-pseudonorephedrine. This process yielded a series of β-hydroxy and β-(diphosphino) benzoyloxy(diphosphino)benzamides that were employed in the Tsuji–Trost asymmetric allylic alkylation process. It was determined that the diastereomeric geometry of the norephedrine series was superior to that of the pseudonorephedrine-based ligands. In addition, it was determined that the norephedrine-based β-(o-diphosphino)benzoyloxy(o-diphosphino)benzamide afforded the best enantiomeric ratio (94:6) favoring the (S)-enantiomer.

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2-(Diphenylphosphino)-N-(1R,2S)-1-hydroxy-1-hydroxy-1-phenyl-2-propyl)benzamideC28H25NO2P[α]D23=-15.6 (c 0.10, CHCl3)Source of chirality: (1R,2S)-norephedrineAbsolute configuration: (1R,2S)

2-(Diphenylphosphino)-N-(1S,2S)-1-hydroxy-1-hydroxy-1-phenyl-2-propyl)benzamideC28H25NO2P[α]D24=+11.3 (c 0.10, CHCl3)Source of chirality: (1S,2S)-pseudo norephedrineAbsolute configuration: (1S,2S)

(1R,2S)-2-(2-Diphenylphosphino)benzamido)-1-phenylpropyl 2-(diphenylphosphino)benzoateC47H39NO3P2[α]D23=+7.8 (c 0.10, CHCl3)Source of chirality: (1R,2S)-norephedrineAbsolute configuration: (1R,2S)

(1S,2S)-2-(2-Diphenylphosphino)benzamido)-1-phenylpropyl 2-(diphenylphosphino)benzoateC47H39NO3P2[α]D23=-16.9 (c 0.10, CHCl3)Source of chirality: (1S,2S)-pseudonorephedrineAbsolute configuration: (1S,2S)