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Total Synthesis of Salicylihalamides A and B
Author(s) -
Herb Christian,
Bayer Alexander,
Maier Martin E.
Publication year - 2004
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.200400617
Subject(s) - alkene , chemistry , aldehyde , aldol reaction , double bond , metathesis , stereochemistry , ring closing metathesis , hydroboration , combinatorial chemistry , organic chemistry , catalysis , polymerization , polymer
The paper illustrates two efficient routes to macrolactone 19 containing a 3‐( para ‐methoxybenzyloxy)propyl side chain at C‐15. The chiral center at C‐15 was introduced by a Noyori reduction of keto ester 5 . The intermediate common to both routes, aldehyde 8 , was prepared from keto ester 5 . The subsequent chain extension utilized Evans aldol reactions. The first route leads to the alkene 14 , which was used, after hydroboration, for a Suzuki cross‐coupling reaction with vinyl iodide 15 . The derived seco acid 18 was converted into the macrolactone 19 by a Mitsunobu lactonization by using immobilized triphenylphosphine. Alternatively, an aldol reaction of 8 with the 4‐pentenoyl derivative 20 was used to prepare alkene 26 . This building block led to ester 28 , which could also be converted into macrolactone 19 by the classical ring‐closing metathesis. After conversion of the C‐15 side chain to the corresponding aldehyde, the enamide was introduced through hemiaminal formation and formal elimination of water. Separation of the double‐bond isomers and removal of the silyl protecting groups provided salicylihalamides A ( E )‐ 1 and B ( Z )‐ 1 .