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Model Studies for a Ring‐Closing Metathesis Approach to the Bafilomycin Macrolactone Core from a 2,2‐Dimethoxy Tetraenic Ester Precursor
Author(s) -
Chevalley Alice,
Prunet Joëlle,
Mauduit Marc,
Férézou JeanPierre
Publication year - 2013
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.201300559
Subject(s) - metathesis , chemistry , isomerization , ring closing metathesis , double bond , salt metathesis reaction , grubbs' catalyst , ring (chemistry) , diene , combinatorial chemistry , stereochemistry , catalysis , organic chemistry , polymer , natural rubber , polymerization
A ring‐closing metathesis strategy is reported for the construction of the 16‐membered macrolactone core of the bafilomycins. One decisive key feature is the presence of a 2,2‐dimethoxyketal functionality at C‐2 that provides the required flexibility to the tetraenic ester precursor, allowing the ring‐closing metathesis reaction to take place. Three different model esters of increasing complexity were successfully subjected to the 1,3‐diene‐ene ring‐closing metathesis reaction. The best promoter for the simplest esters was the Grubbs first‐generation precatalyst. A Hoveyda–Grubbs‐type trifluoromethylamido‐containing precatalyst developed by Mauduit's group gave satisfactory results for the most complex ester. In all experiments, the 12‐ Z ‐configured isomer was obtained as the major product. Subsequent microwave‐promoted methanol elimination was achieved on the simplest model compound using camphorsulfonic acid (CSA) as a catalyst. Under these conditions, a E to Z isomerization of the double bond at C‐4, as well as ca. 50 % isomerization of the 12‐ Z double bond into the corresponding 12‐ E isomer, were observed.