Atropodiastereoselective Cleavage of Configurationally Unstable Biaryl Lactones with Amino Acid Esters

Abstract

AbstractAn 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)