The ability to differentiate and selectively activate remote C-H bonds represents a perennial challenge in the field of C-H activation. Since its first report in 2012, a now-established \"directing template\" (DT) approach remains demonstrably effective for the functionalization of remote C-H bonds. As selectivity is hypothesized to be principally determined by the optimal positioning of the reactive catalyst to a target C-H bond, a DT\'s spatial factors are particularly important toward achieving high selectivity, though a systematic study on its requisite factors remain unelucidated. Through an in-depth analysis of 119 structurally unique published remote DTs, this report summarizes the key factors that are central toward achieving high selectivity at defined aryl positions, which are experimentally corroborated through the development of new aliphatic meta and para-selective DTs for electronically unbiased arenes. These empirical rules, which summarize key distance and geometric factors, are expected to be useful tools for the future development of site-selective arene C-H activation as well as other reactions that rely on covalent/noncovalent DT-mediated remote regioselection.

Cinnamate derivatives are very useful as UV protectors in nature and as sunscreen reagents in daily life. They convert harmful UV energy to thermal energy through effective nonradiative decay (NRD) including trans → cis photoisomerization. However, the mechanism is not simple because different photoisomeirzation routes have been observed for different substituted cinnamates. Here, we theoretically examined the substitution effects at the phenyl ring of methylcinnamate (MC), a non-substituted cinnamate, on the electronic structure and the NRD route involving trans → cis isomerization based on time-dependent density functional theory. A systematic reaction pathway search using the single-component artificial force-induced reaction method shows that the very efficient photoisomerization route of MC can be essentially described as \"1ππ* (trans) → 1nπ* → T1 (3ππ*) → S0 (trans or cis)\". We found that for efficient 1ππ* (trans) → 1nπ* internal conversion (IC), MC should have the substituent at the appropriate position of the phenyl ring to stabilize the highest occupied π orbital. Substitution at the para position of MC slightly lowers the 1ππ* state energy and photoisomerization occurs via a slightly less efficient \"1ππ* (trans) → 3nπ* → T1 (3ππ*) → S0 (trans or cis)\" pathway. Substitution at the meta or ortho positions of MC significantly lowers the 1ππ* state energy so that the energy barrier of IC (1ππ* → 1nπ*) becomes very high. This substitution leads to a much longer 1ππ* state lifetime than that of MC and para-substituted MC, and a change in the dominant photoisomerization route to \"1ππ* (trans) → C[double bond, length as m-dash]C bond twisting on 1ππ* → S0 (trans or cis)\". As a whole, the \"1ππ* → 1nπ*\" IC observed in MC is the most important initial step for the rapid change of UV energy to thermal energy. We also found that the stabilization of the π orbital (i) minimizes the energy gap between 1ππ* and 1nπ* at the 1ππ* minimum and (ii) makes the 0-0 level of 1ππ* higher than 1nπ* as observed in MC. These MC-like relationships between the 1ππ* and 1nπ* energies should be ideal to maximize the \"1ππ* → 1nπ*\" IC rate constant according to Marcus theory.