Premium
gem ‐Dihalocyclopropanes as Building Blocks in Natural‐Product Synthesis: Enantioselective Total Syntheses of ent ‐Erythramine and 3‐ epi ‐Erythramine
Author(s) -
Stanislawski Pauline C.,
Willis Anthony C.,
Banwell Martin G.
Publication year - 2007
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.200700155
Subject(s) - chemistry , diastereomer , enantioselective synthesis , silyl ether , stereochemistry , enantiomer , yield (engineering) , total synthesis , bond cleavage , medicinal chemistry , silylation , organic chemistry , catalysis , materials science , metallurgy
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 π‐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 ).