I was glad to see a nice amide alkylation reaction as part of a total synthesis of (+)-bermudenynol recently reported in Angewandte by Kim and co-workers from Seoul National University. The natural product, the structure of which is shown below, contains an 8-membered ring. We all know how difficult it is to build these kinds of scaffolds. In fact, the authors failed miserably in their attempts to use the ring-closing metathesis, which is the workhorse of medium ring construction. Instead, they turned to a much riskier proposition, namely an attempt to develop a route to the allyl bromide-based substrate shown below and subject it to amide enolate-induced cyclization. Surprisingly, the reaction worked really well, which is interesting considering how infrequent amide enolate alkylations are. There are other interesting features in this synthesis, but amide alkylation is the centerpiece of the approach. The polyhalogenated structure of (+)-bermudenynol also reminded me of some interesting molecules shown by Prof. Chris Braddock (Imperial College) in his talk here at the University of Toronto a couple of days ago.

http://onlinelibrary.wiley.com/doi/10.1002/anie.201308077/abstract