Tuesday, July 10, 2012

MacMillan's Latest - Almost Autocatalysis?

There's been a veritable treasure trove of interesting reactions in JACS over the past month. One particular ASAP caught my eye today: the latest SOMO-organocatalysis reaction from the MacMillan group at Princeton University.

Back up a second, SOMO? Organocatalysis? For those readers normally not nose-first in organic journals, I'll explain a little. SOMO stands for singly-occupied molecular orbital, which means there's radical chemistry afoot! The initial intermediate in many of these reactions, an enamine, reacts with a single-electron oxidant to form a radical cation, which functions as a sort of chiral radical nucleophile...a rare duck.

Future Organocatalyst?
Pyrrolidine Power!
Organocatalysis utilizes small molecules - amines, urea derivatives, hydrogen-bond donors, or small peptides - to accelerate chemical reactions. MacMillan himself gives a good short course on the topic. Organocatalysis bridges the synthetic and biochemical worlds, adapting Nature's enzymatic tricks into new reactivity.

So, why highlight this reaction? Ever since the Soai reaction, a zinc-catalyzed alkylation first reported in 1995, chemists have been enthralled with autocatalysis, the idea that the product of a given reaction could serve as its own catalyst. In theory, you could start with a tiny bit of an (almost) racemic catalyst, and wind up with a fast, highly selective reaction.

Note the similarity between the catalyst (a pyrrolidinone) and the product (a pyrrolidine). Clip off the nosyl protecting group, and I'd believe that product capable of catalyzing its own formation. Now, I'm not usually a betting person, but I like to look skeptically for what's not mentioned. In this case, only two of the products exhibit the same 2,5 substitution as the catalysts, and the authors mention catalyst development only indirectly. 

I'll offer anyone 3:1 odds that, in the next year, an autocatalytic version of this reaction pops up.

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