Synthesis of diphosphite ligands derived from glucopyranoside and their application in the Cu-catalyzed asymmetric 1,4-addition of organozinc to enones

Novel chiral diphosphite ligands derived from glucopyranoside and H8-binaphthol were synthesized, and successfully employed in the Cu-catalyzed asymmetric 1,4-addition of organozinc reagents dimethylzinc, diethylzinc, and diphenylzinc to cyclic and acyclic enones with up to 96% ee. The stereochemically matched combination of d-glucopyranoside backbone and (R)-H8-binaphthyl in the ligand 2,4-bis{[(R)-1,1′-H8-binaphthyl-2,2′-diyl] phosphite}-phenyl 3,6-anhydro-β-d-glucopyranoside was essential for inducing high enantioselectivity. A significant dependence of stereoselectivity on the type of enones and the ring size of cyclic enones was observed. Moreover, the sense of the enantiodiscrimination of the products was mainly determined by the configuration of the H8-binaphthyl moieties.

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2,4-Bis{[(R)-1,1′-H8-binaphthyl-2,2′-diyl] phosphite}-phenyl 3,6-anhydro-β-d-glucopyranosideC52H52O9P2[α]D20=-255 (c 0.4, CH2Cl2)Source of chirality: d-glucose and H8-BINOLAbsolute configuration: (1S,2R,3S,4R,5R,Ra,Ra)

2,4-Bis{[(S)-1,1′-H8-binaphthyl-2,2′-diyl] phosphite}-phenyl 3,6-anhydro-β-d-glucopyranosideC52H52O9P2[α]D20=+230 (c 0.4, CH2Cl2)Source of chirality: d-glucose and H8-BINOLAbsolute configuration: (1S,2R,3S,4R,5R,Sa,Sa)