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Route Scouting towards a Methyl Jasmonate Precursor
Author(s) -
Chapuis Christian,
Walther Eric,
Robvieux Fabrice,
Richard ClaudeAlain,
Goumaz Laurent,
de Saint Laumer JeanYves
Publication year - 2016
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201500257
Subject(s) - chemistry , yield (engineering) , total synthesis , isomerization , cyclopentanone , methyl jasmonate , sequence (biology) , stereochemistry , aldol reaction , organic chemistry , catalysis , biochemistry , materials science , metallurgy , gene
For the synthesis of methyl jasmonate ( 1 ), via the strategic intermediates 3, 4 , and 6a , we constructed a synthetic network via the diverse intermediates 7 – 10, 13, 14, 17 , and 18 . This allowed us to compare the efficiency of more than 20 novel routes. The most productive pathway with a total yield of 38% is represented by the sequence→ 5a → 5m → 13b → 13a → 6a → 4 and proceeds via sequential bromination, basic elimination, decarbomethoxylation, isomerization, and finally Lindlar hydrogenation. The shortest selective way, 2a →[( E , E )‐ 12b ]→ 3 → 4 , is a two‐pot sequence using a modification of Naef 's method, based on an aldol condensation between inexpensive cyclopentanone ( 2a ) and crotonaldehyde, with in situ CoreyChaykovsky cyclopropanation under phase transfer conditions. The key intermediate 3 was then simply pyrolyzed to afford 4 in 27% total yield. The alternative isomerization method via the six‐step deviation→ 5a → 5c → 8c → 13a → 6a → 4 was longer, although more efficient, with a total yield of 32%. Alternatively, a yield of 34% was obtained via the five‐step sequence→ 5a → 5c → 2h → 2i → 4 . Another favored six‐step pathway,→ 5a → 5c → 2h → 17a → 14a → 4 afforded the target compound in 35% total yield.