Stereoselectivities were predicted for the allylation of benzaldehyde using allyltrichlorosilanes catalyzed by 18 axially chiral bipyridine N,N′-dioxides. This was facilitated by the computational toolkit AARON (Automated Alkylation Reaction Optimizer for N-oxides), which automates the optimization of all of the required transition-state structures for such reactions. Overall, we were able to predict the sense of stereoinduction for all 18 of the catalysts, with predicted ee's in reasonable agreement with experiment for 15 of the 18 catalysts. Curiously, we find that ee's predicted from relative energy barriers are more reliable than those based on either relative enthalpy or free energy barriers. The ability to correctly predict the stereoselectivities for these allylation catalysts in an automated fashion portends the computational screening of potential organocatalysts for this and related reactions. By studying a large number of allylation catalysts, we were also able to gain new insight into the origin of stereoselectivity in these reactions, extending our previous model for bipyridine N-oxide-catalyzed alkylation reactions (Organic Letters 2012, 14, 5310). Finally, we assessed the potential performance of these bipyridine N,N′-dioxide catalysts for the propargylation of benzaldehyde using allenyltrichlorosilanes, finding that two of these catalysts should provide reasonable stereoselectivities for this transformation. Most importantly, we show that bipyridine N,N′-dioxides constitute an ideal scaffold for the development of asymmetric propargylation catalysts and, along with AARON, should enable the rational design of such catalysts purely through computation.

Enantioselectivities for the allylation and propargylation of benzaldehyde catalyzed by bipyridine N,N'-dioxides were predicted using popular DFT methods. The results reveal deficiencies of several DFT methods while also providing a new explanation for the stereoselectivity of these reactions. In particular, even though many DFT methods provide accurate predictions of experimental ee's for these reactions, these predictions sometimes stem from qualitatively incorrect transition states. Overall, B97-D/TZV(2d,2p) provides the best compromise between accurate predictions of low-lying transition states and stereoselectivities for these reactions. The origin of stereoselectivity in these reactions was also examined, and arises from electrostatic interactions within the chiral electrostatic environment of a hexacoordinate silicon intermediate; the previously published transition state model for these reactions is flawed. Ultimately, these results suggest two strategies for the design of highly stereoselective catalysts for the propargylation of aromatic aldehydes, and pave the way for the computational design of novel catalysts for these reactions.

Stacking interactions involving substituted contorted hexabenzocoronene (c-HBC) with C were studied at the B97-D3M(BJ)/TZVPP//B97-D/TZV(2d,2p) level of theory. First, we showed that substituent effects in benzeneC complexes are uncorrelated with those in the benzene sandwich dimer, underscoring the importance of local, direct interactions in substituent effects in stacking interactions. Second, we showed that c-HBC preferentially forms stacked homodimers over complexes with C; however, if the bowl depth of c-HBC is increased beyond 1.25 Å, the c-HBCC complex becomes preferred over the c-HBC homodimer. Ultimately, we showed that the perfluorination of c-HBC leads to sufficient curvature to allow the c-HBCC heterodimers to form preferentially over c-HBC homodimers, suggesting the possibility of the development of c-HBC derivatives that assemble into alternating stacks with C.