Tropos deoxycholic acid-derived biphenylphosphites: synthesis, stereochemical characterization and use as chiral ligands in the copper catalyzed conjugate addition of diethylzinc to acyclic enones

Three new deoxycholic acid-based 5,5′-substituted biphenylphosphites, 2–4, were synthesized and their stereochemical features were examined by CD and NMR spectroscopy, which allowed us to determine the sense of twist of the substituted biphenyl moiety as well as the extent of its prevalence in different solvents. Phosphites 1–4 were used as chiral ligands in the copper catalyzed conjugate addition of diethylzinc to acyclic enones, affording the alkylation products with ees up to 65%. The results obtained allowed a correlation between asymmetric induction and the sense of twist of the biphenylphosphite moiety of the chiral inducers.

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Methyl 3α-acetyloxy-12α-(5,5′-dibromobiphenyl-2,2′-diyl)phosphite-5β-cholan-24-oateC39H49Br2O7P[α]D22=+24.3 (c 1.00, CH2Cl2)Source of chirality: natural source

Methyl 3α-acetyloxy-12α-(5,5′-diphenylbiphenyl-2,2′-diyl)phosphite-5β-cholan-24-oateC51H59O7P[α]D24=+28.6 (c 0.95, CH2Cl2)Source of chirality: natural source

Methyl 3α-acetyloxy-12α-(5,5′-diisopropylbiphenyl-2,2′-diyl)phosphite-5β-cholan-24-oateC45H63O7P[α]D25=+52.0 (c 1.03, CH2Cl2)Source of chirality: natural source