Temperature-Dependent Regioselectivity of Nucleophilic Aromatic Photosubstitution. Evidence That Activation Energy Controls Reactivity

Abstract

Irradiation (λ > 330 nm) of 2-chloro-4-nitroanisole (1) at 25 °C in aqueous NaOH forms three substitution photoproducts: 2-methoxy-5-nitrophenol (2), 2-chloro-4-nitrophenol (3), and 3-chloro-4-methoxyphenol (4), in chemical yields of 69.2%, 14.3%, and 16.5%. The activation energies for the elementary steps from the triplet state at 25 °C were determined to be 1.8, 2.4, and 2.7 kcal/mol, respectively. The chemical yields of each of the three products were determined for exhaustive irradiations at 0, 35, and 70 °C. The variation with temperature of the experimental yields is reproduced almost exactly by the yields calculated with the Arrhenius equation. This indicates that activation energy is the fundamental property related to regioselectivity in nucleophilic aromatic photosubstitution of the S(N)2 Ar* type. The many methods proposed for predicting regioselectivity in reactions of this type have had limited success and have not been related to activation energy.

Switch in Selectivity for Formal Hydroalkylation of 1,3‐Dienes and Enynes with Simple Hydrazones

“…[2] Thepower of using catalysis to attain exquisitely selective transformations is elegantly exploited by nature,w hich can convert identical starting materials into av ariety of diversified products by using enzymes.I nspired by the extraordinary selectivity of biocatalysis,s everal strategies have been devoted to gaining an analogous level of regio-enriched products over facile innate reactivity. [3] Examples include a) installation of different protecting or directing groups [4] to overcome the inherent sterically and electronically biased factors,b)modification of reaction parameters,s uch as solvent, [5] temperature, [6] additives, [7] etc., and c) design and manipulation of the catalyst system. [8] As Tr ost has asserted, engineering ac atalyst that completely overrides inherent regio-or chemoselectivity to give exclusively the desired product requires creativity and insight.…”