Route Scouting towards a Methyl Jasmonate Precursor

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 20novel routes. The most productive pathway with a total yield of 38% is represented by the sequence5a5m13b13a6a4 and proceeds via sequential bromination, basic elimination, decarbomethoxylation, isomerization, and finally Lindlar hydrogenation. The shortest selective way, 2a[(E,E)-12b]34, 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 deviation5a5c8c13a6a4 was longer, although more efficient, with a total yield of 32%. Alternatively, a yield of 34% was obtained via the five-step sequence5a5c2h2i4. Another favored six-step pathway,5a5c2h17a14a4 afforded the target compound in 35% total yield.