Atropodiastereoselective Cleavage of Configurationally Unstable Biaryl Lactones with Amino Acid Esters


  • Novel Concepts in Directed Biaryl Synthesis, 111. Part 110: Ref.1


An improved procedure for the stereoselective synthesis of axially chiral biaryl systems is described, by atroposelective ring cleavage of configurationally unstable lactone-bridged biaryls with amino acid esters as inexpensive and efficient chiral N-nucleophiles. Starting with configurationally unstable lactones of type 2, which are readily accessible by intramolecular Heck reaction of the respective bromo esters 1, the atroposelective ring cleavage succeeds by using a broad variety of amino acid esters of type 5, leading to configuratively stable axially chiral biaryl amides 3 in good chemical yields and excellent diastereomeric ratios of up to > 99.5:0.5. The axial configurations of the products were assigned by quantum chemical CD calculations and by X-ray structure analysis. From the diastereomerically pure ring cleavage products, the chiral auxiliary can be eliminated, e.g., by treatment with sodium nitrite to give the respective nitrogen-free biaryl enantiomers of type 9, with merely axial chirality. By using a standard solid-phase Fmoc strategy, this approach allows to incorporate the biaryl fragment into peptide strands. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)