New syntheses of E7389 C14-C35 and halichondrin C14-C38 building blocks: double-inversion approach.
With sequential use of catalytic asymmetric Cr-mediated coupling reactions, E7389 C14-C35 and halichondrin C14-C38 building blocks have been stereoselectively synthesized. The C19-C20 bond is first formed via the catalytic asymmetric Ni/Cr-mediated coupling, i.e., 8 + 9 --> 10 (90%; dr = 22:1), in which vinyl iodide 8 is used as the limiting substrate. The C23-C24 bond is then formed via the catalytic asymmetric Co/Cr-mediated coupling, i.e., 13 + 14 --> 4 (82%; dr = 22:1), in which the alkyl-iodide bond in 14 is selectively activated over the vinyl-iodide bond. The catalytic asymmetric Ni/Cr-mediated reaction is employed to couple C14-C26 segment 19 with E7389 C27-C35 segment 20 (91%; dr = >55:1). In this synthesis, the C23-O bond is stereoselectively constructed via a double-inversion process, i.e., 21 --> 22, to furnish E7389 C14-C35 building block 22 in 84% yield. The same synthetic sequence has been employed to synthesize halichondrin C14-C38 building block 18b, i.e., 16a + 19 --> 18b.
Kim
Dae-Shik
DS
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.
Dong
Cheng-Guo
CG
Kim
Joseph T
JT
Guo
Haibing
H
Huang
Jian
J
Tiseni
Paolo S
PS
Kishi
Yoshito
Y
D002384:Catalysis; D004988:Ethers, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D009532:Nickel / Q000737:chemistry
D004988:Ethers, Cyclic; C022838:nickel chloride; D009532:Nickel