Tonight I am not covering anything from the recent literature. My post is very much need-driven, rather than current literature-based. My lab has contemplated ways of putting together alpha-substituted proline derivatives. Our long-standing plan is to use them in a range of reactions, including our peptide macrocyclization. While you can buy the alpha-methyl variant, good luck finding something that is a bit more elaborate. In this regard, you might say that there has to be a way to use sigmatropic reactions and induce transfer of a nitrogen-bound group to the alpha carbon. Something like this rings a bell and formally corresponds to the Stevens rearrangement. The trouble is, this process is never clean due to the competing Sommelet-Hauser rearrangement. By the way, there is nothing wrong with this “competition” because the Sommelet-Hauser process is equally attractive from the endpoint perspective. However, the rule of reciprocity tells us that, in this case, the product will be contaminated by the amino acid derivative emanating from the Sommelet rearrangement.
There is a delightful Angewandte paper by Tayama and co-workers that shows how control can in fact be exercised. Take a look. I definitely want to use some of these amino acid building blocks in our chemistry. There is something really interesting about potassium tert-butoxide (I’ve also heard that if you have a bottle of this stuff, you do not need any transition metal catalysts anymore… I refer to that curious Grubbs/Stoltz paper, of course).