Olefin metathesis and isomerization: From undesired side reactions to useful synthetic methodology

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

“…We started with the most common catalyst, the second generation Grubbs’ catalyst. In order to suppress undesired double bond isomerization reactions [51–52] we tried to avoid high reaction temperatures, which may cause catalyst decomposition to isomerization active species. This phenomenon has often been observed for second generation catalysts [53].…”

Synthesis of a library of tricyclic azepinoisoindolinones

“…A possible pathway for decomposition is indicated by the benzylic/allylic methine oxidation product 6 . The ability of Ti(OiPr) 4 to induce alkene isomerization during the ring-closing metathesis reaction is noteworthy; while there are a number of additives known to decrease the rate of isomerization in RCM [33–35], we are unaware of any previous report on an alkene-isomerization-promoting effect of an additive in this reaction. We can speculate that the presence of Ti(OiPr) 4 stabilizes the ruthenium alkylidene complex and, thus allows product isomerization to take place during and after the RCM reaction (see below).…”

2-Methyltetrahydrofuran as a Solvent of Choice for Spontaneous Metathesis/Isomerization Sequence

“…Double bond isomerization, for many years treated as an undesired side reaction, has traditionally been attributed to the formation of ruthenium hydrides, 22 although recent studies indicate that also other ruthenium species such as nanoparticles 23 or dimers 24 may also be responsible for this by-process. Because the ruthenium species responsible for the double bond isomerization differ in structure and origin, 25 it was of key importance to find the conditions under which C–C bond migration will be induced at a certain moment in the sequence after full completion of the metathesis reaction and will not be competing with the latter process. Pioneering research on this methodology was performed by Snapper et al 26 Upon treatment with molecular hydrogen, cyclic allyl ethers obtained in ring-closing metathesis (RCM) were transformed into their corresponding vinyl isomers.…”