{"id":174,"date":"2024-11-28T14:11:27","date_gmt":"2024-11-28T06:11:27","guid":{"rendered":"http:\/\/chem-fan.com\/?p=174"},"modified":"2024-11-28T16:10:25","modified_gmt":"2024-11-28T08:10:25","slug":"radicals-nucleophilic-or-electrophilic","status":"publish","type":"post","link":"http:\/\/chem-fan.com\/?p=174","title":{"rendered":"Radicals: Nucleophilic or Electrophilic?"},"content":{"rendered":"\n

First question\uff01<\/strong><\/p>\n\n\n\n

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Is radical Nucleophilic or Electrophilic species?<\/strong><\/p>\n\n\n\n

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We know that radicals are often considered electron-deficient species that don’t satisfy the octet rule. However, Electron Deficiency \u2260 Electrophilicity<\/strong>. In fact, radicals can exhibit either nucleophilic or electrophilic behavior, depending on their tendency to target sites of higher or lower electron density. Radical polarity matching has been one of the most critical aspects of modern radical reaction kinetics research, greatly influencing radicals’ reactivity and selectivity. Recognizing these factors helps us understand, control and design radical reactions<\/p>\n\n\n\n

Frontier molecular orbital theory offers deeper insight into radical behavior. The SOMO (Singly Occupied Molecular Orbital) of a radical can interact with both the HOMO and LUMO of a reactant, lowering the transition state energy in both cases. Interaction with the LUMO clearly reduces energy, but the same is true for interaction with the HOMO.<\/p>\n\n\n

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The interaction of the SOMO with the HOMO and LUMO of a molecule<\/em><\/figcaption><\/figure>\n<\/div>\n\n\n

Radicals with high-energy SOMOs tend to react quickly with molecules that have low-energy LUMOs, exhibiting characteristics of nucleophiles. Conversely, radicals with low-energy SOMOs readily react with high-energy HOMOs, behaving like electrophiles. Therefore, the former are classified as nucleophilic radicals, while the latter are considered electrophilic radicals.<\/p>\n\n\n

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Frontier orbital interactions for nucleophilic\/electrophilic radicals<\/em><\/figcaption><\/figure>\n<\/div>\n\n\n

Application<\/strong><\/p>\n\n\n

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Radical polarity effects in organic synthesis.<\/em><\/figcaption><\/figure>\n<\/div>\n\n\n

Notably, nucleophilic radicals are superior in both Giese \u03c0-additions to electron-deficient alkenes and Minisci aryl substitutions of pyridiniums. Conversely, electrophilic radicals are better suited for (anti-Markovnikov) Kharasch \u03c0-additions to electron-rich alkenes, as well as homolytic aromatic substitutions (SH<\/sub>Ar) of electron-rich arenes. Similarly, homolytic substitution (SH<\/sub>2) reactions are strongly influenced by polarity. For example, HAT of hydridic C\u2013H bonds are best mediated by an electrophilic radical (N\u2022<\/sup>, O\u2022<\/sup>), while abstraction of electrophiles by either group- (e.g., xanthate) or halogen atom transfer (XAT) are often facilitated by nucleophilic radicals (Sn\u2022<\/sup>, Si\u2022<\/sup>).<\/p>\n\n\n

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Key mechanisms in radical chemistry and examples of polarity effects in each.<\/em><\/figcaption><\/figure>\n<\/div>\n\n\n

A clear understanding of radical nucleophilicity and electrophilicity enhances the unique potential of radical chemistry, guiding the design and development of novel, efficient, and highly selective radical reactions. <\/p>\n\n\n\n

For examlple, Roberts and colleagues demonstrated site-selective hydrogen atom transfer (HAT) reactions in butyrolactone using either nucleophilic boron radicals or electrophilic tert-butoxy radicals.<\/p>\n\n\n\n

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Though the bond dissociation energies (BDE) of the two C-H bonds involved were similar. However, the t-BuO\u00b7 selectively abstracted hydrogen from the O \u03b1-position, whereas the Et3<\/sub>N-BH2<\/sub>\u00b7 abstracted the hydrogen at the carbonyl group \u03b1-position.<\/p>\n\n\n\n

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In this reaction, the key frontier orbitals involve the radical’s SOMO interacting with either the \u03c3 or \u03c3* orbital of the C-H bond. Due to the high electronegativity of oxygen, the tert-butoxy radical (t-BuO\u00b7) has a relatively low-energy SOMO, which interacts strongly with high-energy orbitals adjacent to electron-donating (X) substituents (as in D<\/em><\/strong>).<\/p>\n\n\n\n

In contrast, the triethylamine-borane radical (Et\u2083N-BH\u2082\u00b7) has a high-energy SOMO, making it more likely to interact with lower-energy \u03c3* orbitals of C-H bonds (like A<\/em><\/strong>). Thus, for Et\u2083N-BH\u2082\u00b7, A<\/em><\/strong> is more reactive than C<\/em><\/strong>, while for t-BuO\u00b7, D<\/em><\/strong> is more reactive than B<\/em><\/strong>.<\/p>\n\n\n\n

How to Evaluate Radical Polarity?<\/strong><\/p>\n\n\n\n

Radical polarity can be roughly evaluated using the following four methods.<\/p>\n\n\n

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