Organocatalytic Relay Cascade Reactions

kilomentor | 25 November, 2010 11:15

The other day, I was reading journals in the University of Toronto chemistry library. A hot topic for synthetic chemists is asymmetric organocatalytic cascade/domino reactions. An example of such a publication is Angew. Chem. Int. Ed. 2009, 48, 9834-9838 which in turn cites many pieces of similar prior art.

It is indisputable that these reactions are promising approaches for rapid assembly of complex asymmetric structures but they do not pretend to be, and they should not be mistaken to be, methods that could be used for scaled up processes. Looking at the cited paper, although atom economy is identified as an advantage of the methodology, two catalysts are used, each in 15% molar ratio. These particular catalysts had molecular weights of 582 and 519. No procedure for recovery and reuse of these ‘catalysts’ in reusable purities was reported. The atom economy when these losses are taken into account is not so attractive.

Another point is that for a process that is run at scale it is the isolated yield of pure product that goes into calculating the overall yield but no method is provided for separating the enantioselectively and diastereoselectively formed principal products from the rest of the reaction soup.

This is not to say that what has been achieved is not admirable but process chemist readers should not make the mistake of thinking for one moment that such technology is ready for process adoption.