Total Synthesis of the Annonaceous Acetogenin (+)-Asimicin. Development of a New Bidirectional Strategy

The total synthesis of the Annonaceous acetogenin (+)-asimicin is described. The approach employs the ( R )-α-OSEM allylic stannane 7 of >95% ee and the dialdehyde 8 obtained from ( S,S )-diethyl tartrate. Addition of 7 to 8 in the presence of InCl 3 afforded the bis-adduct 9 in 71% yield. Tosylation and treatment with TBAF led to the core bis-tetrahydrofuran intermediate, diol 11, in 78% yield. Mono tosylation ( n -BuLi, TsCl, THF−DMSO) and subsequent hydrogenolysis with LiBEt 3 H gave alcohol 14 . The iodide 15 was coupled with the higher-order vinylcyanocuprate to afford olefin 30 . This was converted to diol 31 of high ee by the Sharpless protocol. This diol yielded the epoxide 33 via the mono-trisylate 32 . Addition of ( R )-lithio-2-(OTBS)-3-butyne in the presence of BF 3 ·OEt 2 afforded the alcohol 34 . The SEM derivative 35 was treated with TBAF, and the resulting alcohol was converted to the butenolide 38 by a sequence involving treatment with (CF 3 CO) 2 O, then Pd(PPh 3 ) 4, CO, THF−H 2 O, and finally AgNO 3 /silica gel. Cleavage of the SEM protecting group with PPTS in ethanol afforded (+)-asimicin ( 39 ).