First asymmetric total synthesis of Millpuline B

Millpuline B (1), isolated from Millettia pulchra, is a naturally occurring bioactive compound with a chiral center. Herein, we report the first total syntheses of both (+/-)-Millpuline B from commercal available 6,7-dihydro-4(5H)-benzofuranone (4) using Grignard reaction and asymmetric CBS reduction as the key steps. Millpuline B (1) was synthesized with up to 94.3% enantiomeric excess and the Mosher's methods were used to elucidate the absolute configuration of key intermediates 11 and 12. All of the synthetic steps could be carried out on gram-scale.