Summary of Efforts toward a Loline Synthesis

This summer I have been attempting a total synthesis of the natural compound loline. The summer commenced with running familiar reactions at larger scales to move more material forward in the route. We were able to improve the yield of the RCM (ring closing metathesis) to an impressive 89%, but this was coupled with continually inconsistent results with the preceding acylation. I then ran three new reactions to make the methyl ester carbamate that was critical to our 2011 synthesis. After some initial troubleshooting, I was able to produce the desired product in good yield. Unfortunately, the following reduction with Dibal-H had a negligible yield despite several revisions to the reaction and work up conditions. There are about four remaining steps to loline past this point, so it would be a futile pursuit to continue running this reaction.

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