gem-Dihalocyclopropanes as building blocks in natural-product synthesis: enantioselective total syntheses of ent-erythramine and 3-epi-erythramine.
ent-Erythramine ((-)-1), the enantiomer of the alkaloid erythramine, was prepared in 15 steps from known compounds. The first of three pivotal bond-forming steps in the synthesis was a Suzuki-Miyaura cross-coupling reaction of the starting materials to give a bis-silyl ether. The second involved silver(I)-induced electrocyclic ring opening of the gem-dichlorocyclopropane formed in the next step and trapping of the ensuing pi-allyl cation by the tethered nitrogen atom to give, following cleavage of the allyloxycarbonyl protecting group, an approximately 5:6 mixture of the chromatographically separable diastereoisomeric spirocyclic products. In the third critical bond-forming reaction, the iodide formed from one of the diastereoisomers underwent a radical-addition/elimination reaction sequence that led to (-)-1 in 89 % yield. The application of the same sequence of transformations to the other diastereoisomer afforded 3-epi-(+)-erythramine (3-epi-(+)-1).
Stanislawski
Pauline C
PC
Research School of Chemistry, Institute of Advanced Studies, The Australian National University, Canberra, ACT 0200, Australia.
Willis
Anthony C
AC
Banwell
Martin G
MG
D052117:Benzodioxoles / Q000138:chemical synthesis*; D001688:Biological Products / Q000138:chemical synthesis*; D002853:Chromatography, Liquid; D003521:Cyclopropanes / Q000737:chemistry*; D007546:Isoquinolines / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009584:Nitrogen / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism
D052117:Benzodioxoles; D001688:Biological Products; D003521:Cyclopropanes; D007546:Isoquinolines; C524620:erythramine; D009584:Nitrogen