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Expeditious Asymmetric Synthesis of a Stereoheptad Corresponding to the C(19)–C(27)‐Ansa Chain of Rifamycins: Formal Total Synthesis of Rifamycin S
Author(s) -
Turks Māris,
Huang Xiaogen,
Vogel Pierre
Publication year - 2005
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200400825
Subject(s) - chemistry , aldol reaction , ene reaction , ketone , stereochemistry , enantiomer , total synthesis , aldol condensation , silylation , catalysis , medicinal chemistry , organic chemistry
Abstract In the presence of sulfur dioxide and an acid promoter, (−)‐(1 E ,3 Z )‐2‐methyl‐1‐((1 S )‐1‐phenylethoxy)penta‐1,3‐dien‐3‐yl isobutyrate reacts with ( Z )‐3‐(trimethylsilyloxy)pent‐2‐ene giving a silyl sulfinate intermediate that undergoes, in the presence of palladium catalyst, a desilylation and retro‐ene elimination of SO 2 with formation of (−)‐(1 Z ,2 S ,3 R ,4 S )‐1‐ethylidene‐2,4‐dimethyl‐5‐oxo‐3‐((1 S )‐1‐phenylethoxy)‐heptyl isobutyrate as major product. This ethyl ketone undergoes cross‐aldol reaction with (2 S )‐2‐methyl‐3‐[( tert ‐butyldimethylsilyl)oxy]propanal giving an aldol that is reduced into a stereoheptad corresponding to the C(19)‐C(27)‐segment of Rifamycins with high diastereoselectivity and enantiomeric excess.