カーベノイド化学における"獣"を活用する: 素直な直接核性フッ素メチル化戦略の開発

Bromination and chlorination of aromatic rings by electrophilic aromatic substitution reactions are easily achieved, but fluorination and iodination are difficult to achieve. Fluorine is so reactive that its reaction with benzene is difficult to control, resulting in poor yields of monofluoroaromatic products. To address this, Selectfluor reagent is used as a fluorine source in which a fluorine atom is bonded to a positively charged nitrogen.

Simple aryl halides do not react with nucleophiles. However, nucleophilic aromatic substitutions can be forced under certain conditions, such as high temperatures or strong bases. The mechanism of substitution under such conditions involves the highly unstable and reactive benzyne intermediate. Benzyne contains equivalent carbon centers at both ends of the triple bond, each of which is equally susceptible to nucleophilic attack. This 50–50 distribution of products is...

α-Halogenation of aldehydes and ketones is a reaction involving the substitution of α hydrogens with halogens in the presence of a base.  The reaction begins with the abstraction of  α hydrogen by the base to produce a nucleophilic enolate ion. This intermediate undergoes a subsequent nucleophilic substitution with the halogen to produce a monohalogenated carbonyl compound. If the starting substrate has more than one α hydrogen, it is difficult to stop the reaction...

A method involving the transformation of methyl ketones to carboxylic acids using excess base and halogen is called the haloform reaction. It begins with the deprotonation of α hydrogen to form an enolate ion which reacts with the electrophilic halogen to give an α-halo ketone. The step continues until all the α protons are substituted to form a trihalomethyl ketone. The resulting molecule is unstable, and in the presence of a hydroxide base, it readily undergoes nucleophilic...

Historical perspective
In 1896, the German chemist Paul Walden discovered that he could interconvert pure enantiomeric (+) and (-) malic acids through a series of reactions. This conversion suggested the involvement of optical inversion during the substitution reaction. Further, in 1930, Sir Christopher Ingold described for the first time two different forms of nucleophilic substitution reactions, which are known as SN1 (nucleophilic substitution unimolecular) and SN2 (nucleophilic substitution...

In organic synthesis, the formation of products can be altered by changing the reaction conditions. For example, a dibromo addition product is formed when propene is treated with bromine at room temperature. In contrast, propene undergoes allylic substitution in non-polar solvents at high temperatures to give 3-bromopropene. In order to avoid the addition reaction, the bromine concentration must be kept as low as possible throughout the reaction. This can be achieved using N-bromosuccinimide...