Stoltz, Tambar and Ebner, JACS, 2006, ASAP. DOI: 10.1021/ja0651815
Another short but sweet synthesis by Stoltz, this time of the isopavine alkaloid amurensinine (or at least the enantiomer of the natural product). The biological activity of this target is certainly appealing enough, as it seems to be interest with regard to Parkinsonâ€™s and Alzheimerâ€™s disease. Their synthesis involves C-C and C-H bond insertions, the former with an aryne. Lets start with a bit of C-H activation:
Okay, I guess you’ve seen this style of thing in you undergrad course, but it’s nice to see a real-world example, and a hell of a yield! But there’s a thorny selectivity issue – why only one regioisomer, and why that one? No answer in the paper, even though the same question is posed. Perhaps it’s because the H is para to an OMe, or is it just steric effects… but I can’t actually believe that. On with the C-C activation:
Now that’s a funky transformation. Taking the product of the former reaction, and treating it with an aryne, they get addition and then rearrangement to get the to product in a none-too-shabby yield. With this substrate in hand, they did a diastereoselective reduction with L-Selectride, and an oxidative resolution to set up the asymmetry, requiring only a few more steps to get to the target.