Cyclopropenimines
Our group has introduced cyclopropenimines as a novel class of strong organic Brønsted base (J. Am. Chem. Soc. 2012, 134, 5552; J. Am. Chem. Soc. 2013, 135, 11799). The signature feature of the cyclopropenimine scaffold is the presence of a latent cyclopropenium ion, which is revealed upon protonation of the imino nitrogen. As the smallest ring system that satisfies Hückel’s rules for aromaticity, the 2π-electron cyclopropenium ion provides substantial resonance stability to the conjugate acid of the cyclopropenimine. In comparison to the analogous guanidines, this additional aromatic stabilization renders cyclopropenimines significantly more basic, and places them directly on par with the phosphazenes in terms of basicity.
Enantioselective Catalysis
One of our primary interests with cyclopropenimines has been in regard to their capacity to serve as highly effective enantioselective Brønsted base catalysts. An interesting finding for this program arose from a detailed mechanistic and computational study, performed in collaboration with the group of Prof. Mathew Vetticatt at SUNY-Binghamton, which revealed several notable features of these structures and provided crucial insight into their high efficiencies (J. Am. Chem. Soc. 2014, 136, 10700 and Chem. Sci. 2015, 6, 1537).
Specifically, we discovered the profound impact the dicyclohexylamino substituents have on the efficiency of this catalyst. A combination of X-ray crystallography and computational analysis revealed the unique role these substituents play. Due to their significant steric demand, the four cyclohexyl substituents do not have the freedom of rotation that less demanding substituents have, but are instead geared to one another. This restriction reinforces a long-range, noncovalent C-H---O interaction between one of the cyclohexylamino a-C-H bonds and the hydroxyl group, which in turn constrains the conformational freedom of this key hydrogen bonding functionality. In this way, facile transition state organization is achieved, helping to enable high levels of enantioselection.
In addition to our first generation catalyst, we have reported an improved, second generation catalyst that offers significantly enhanced reactivity, selectivity, and stability (Chem. Sci. 2015, 6, 1537).
Higher-Order Cyclopropenimine Superbases
We have also developed a series of higher-order superbases using cyclopropenimines (J. Am. Chem. Soc. 2015, 137, 10246). These species have enhanced basicities and unique structural characteristics, which serve to significantly expand the repertoire of this class of molecules. Many of these bases are also reasonably easy to synthesize and handle, especially the GC2 bases.