Synthesis of novel chiral bidentatephosphite ligands derived from the pyranoside backbone of monosaccharides and their application in the Cu-catalyzed conjugate addition of dialkylzinc to enones

A series of novel bidentatephosphite ligands, derived from methyl 3,6-anhydro-α-d-glucopyranoside and chlorophosphoric acid diaryl ester, were easily synthesized. These ligands were successfully employed in the Cu-catalyzed asymmetric conjugate 1,4-addition of the organozinc reagents diethylzinc and/or dimethylzinc to enones. The stereochemically matched combination of glucopyranoside and (R)-H8-binaphthyl in ligand 2,4-bis{[(R)-1,1′-H8-binaphthyl-2,2′-diyl] phosphite}-methyl 3,6-anhydro-α-d-glucopyranoside was essential to afford 85% ee for 3-ethylcyclohexanone with an (S)-configuration in THF, using Cu(OTf)2 as a catalytic precursor. When the reaction was carried out at lower temperatures, changing from −10 to −80 °C, a marginal influence of the temperature on the enantioselectivity of the reaction was observed. The presence of the methyl substituent at the 1-position of the glucopyranoside skeleton had a negative effect on the enantioselectivity in the 1,4-addition of ZnEt2 to acyclic enones.

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2,4-Bis{[(R)-1,1′-binaphthyl-2,2′-diyl]phosphite}-methyl 3,6-anhydro-α-d-glucopyranosideC47H34O9P2[α]D20=-321 (c 0.2, CH2Cl2)Source of chirality: d-glucose and BINOLAbsolute configuration: (1S,2R,3S,4R,5R,Ra,Ra)

2,4-Bis{[(S)-1,1′-binaphthyl-2,2′-diyl]phosphite}-methyl 3,6-anhydro-α-d-glucopyranosideC47H34O9P2[α]D20=+502 (c 0.2, CH2Cl2)Source of chirality: d-glucose and BINOLAbsolute configuration: (1S,2R,3S,4R,5R,Sa,Sa)

2,4-Bis{[(R)-1,1′-H8-binaphthyl-2,2′-diyl]phosphite}-methyl 3,6-anhydro-α-d-glucopyranosideC47H50O9P2[α]D20=-126 (c 0.2, 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}-methyl 3,6-anhydro-α-d-glucopyranosideC47H50O9P2[α]D20=+309 (c 0.2, CH2Cl2)Source of chirality: d-glucose and H8-BINOLAbsolute configuration: (1S,2R,3S,4R,5R,Sa,Sa)