Total synthesis of eupomatilones 1, 2, and 5 by enantioselective [2,3]-wittig rearrangement

摘要

In this study, the asymmetric total synthesis of eupomatilones 1, 2, and 5 has been accomplished. These compounds are lignan congeners containing a biaryl system bearing an α-methylene γ-lactone. They were isolated from the Australian shrub Eupomatia bennettii. Two chiral centers were constructed enantioselectively by the asymmetric [2,3]-Wittig rearrangement of highly oxygenated biaryl compounds, using a bis(oxazoline) chiral ligand. Optimization of the key reaction using nBuLi as the base and ether as the co-solvent increased the enantioselectivity to 88-91 % ee. An asymmetric total synthesis of eupomatilones 1, 2, and 5 was carried out. The asymmetric [2,3]-Wittig rearrangement of biarylmethyl ethers was used for the construction of the chiral centers, using a bis(oxazoline) chiral ligand. Optimization of the reaction conditions enabled the synthesis of eupomatilones 1, 2, and 5 with high enantioselectivities (88-91 % ee).