Asymmetric catalysis is a useful way to control the stereochemical outcome of organic reactions. However, only a few chiral catalysts have a broad reaction scope and high stereoselectivity. Many provide only a moderate enantioselectivity, which often prevents their use. Boosting the stereoselectivity of such catalysts using external “help” could make them useful in synthesis.
Xiaowei Li and Yan Zhao, Iowa State University, Ames, USA, have developed a chiral “gate” that controls the access to such a mediocre chiral catalyst and, thus, improves its selectivity. This concept is similar to the way enzymes work. The team used “molecular imprinting” to create a chiral nanospace inside a micelle during polymerization. For this, they added a chiral template molecule (e.g., a peptide) to a micelle made from divinylbenzene (DVB) and the photoinitiator 2,2-dimethoxy-2-phenylacetophenone (DMPA). The micelle surface is crosslinked using a Cu(I)-catalyzed click reaction and the core is polymerized using free radical polymerization. The shape of the chiral template is then replicated in the resulting polymerized nanoparticle (schematically pictured).
The researchers used the imprinted nanoparticles to improve the enantioselectivity of a simple prolinamide. This amide was used as an asymmetric catalyst for an aldol reaction between acetone and p-nitrobenzaldehyde. The template used during polymerization of the micelles included suitable space holders for the catalyst, for the enamine derivative of acetone, and for the aldehyde.
Without the imprinted nanoparticles, the catalyst only achieved 42 % ee. Adding the nanoparticles improved the enantiomeric excess to 96 %. Even a racemic mixture of the catalyst achieved over 70 % ee, which shows that the chiral space in the particles predominantly binds one enantiomer of the catalyst. According to the researchers, molecularly imprinted nanoparticles have the potential to enable practical applications for otherwise “disqualified” chiral catalysts.
- Chiral Gating for Size- and Shape-Selective Asymmetric Catalysis,
Xiaowei Li, Yan Zhao,
J. Am. Chem. Soc. 2019.