A couple of weeks ago I gave a talk at the Gordon Conference on Heterocycles (https://www.grc.org/programs.aspx?id=11391) and got to see my old friend Professor Erick Carreira of ETH (and, of course, a ton of other cool people). Erick gave a really interesting lecture, which was largely dedicated to his lab’s ongoing interests in developing synthetic routes to all possible diastereomers of a given chiral molecule. As you all know, it is the enantioselectivity that is easy: if you need the opposite enantiomer of a given molecule for which an asymmetric route exists, you choose the corresponding enantiomer of your catalyst. In contrast, the development of synthetic strategies that provide controlled access to any given stereoisomer of a target with multiple stereocenters, is in its infancy.
In his talk, Erick described an innovative strategy to access all stereoisomers of cannabinoid receptor activators. The route involves simultaneous use of two chiral catalysts, each of which possessing full control over the configuration of one of the product stereocenters. For their purposes, the Carrera team used a combination of iridium and enamine catalysis. Asymmetric matters aside, I truly enjoyed the way the core of the target was constructed. You can see a brief summary of the route below. There are countless other examples of cannabinoid total synthesis and they look nothing like this original contribution. I particularly like the last step. Stars indicate the fact that all stereoisomers can be prepared at will by choosing the right combination of catalysts.