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Electrophilic C 12 Building Blocks for Alkaloids: 1 , 1 Iterative Organoiron‐Mediated Routes to (±)‐Lycoramine and (±)‐Maritidine
Author(s) -
Stephenson G. Richard,
Roe Caroline,
Sandoe Elizabeth J.
Publication year - 2011
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201001394
Subject(s) - electrophile , chemistry , nucleophile , aryl , alcohol , combinatorial chemistry , reagent , total synthesis , enantioselective synthesis , medicinal chemistry , stereochemistry , organic chemistry , alkyl , catalysis
Aryllithium reagents generated from protected 6‐bromoguaiacol and 2‐bromo‐4,5‐dimethoxybenzyl alcohol derivatives were used to prepare ortho ‐substituted (1‐arylcyclohexadienyl)iron(1+) electrophiles. These were treated with Na + [Me 3 SiCH 2 CH 2 O 2 CCHCN] – to build aryl‐substituted quaternary centres in new examples of 1 , 1 iterative {[η 4 ] → [η 5 ] + → [η 4 ] → [η 5 ] + → [η 4 ]} reaction sequences, which make use of the electrophilicity of the metal complex in two key carbon–carbon bond‐formation steps. MOM protection of the guaiacol was better than SEM for access to the lycoramine skeleton, and TBDPS was best for maritidine. Decomplexation, hydrolysis, and cyclisation completed formal total syntheses of the Amaryllidaceae alkaloids (±)‐lycoramine and (±)‐marididine, establishing the compatibility of the organoiron method with the presence of ortho substituents on the aryl group, and nucleophile addition ipso to the substituted arene.