Synthesis of α-Fluoroketones from Vinyl Azides and Mechanism Interrogation

By replacing an α-hydrogen with a halogen, acid-catalyzed α-halogenation of aldehydes or ketones yields a monohalogenated product
In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...

Ketones with α protons are deprotonated by strong bases like lithium diisopropylamide (LDA) to form enolate ions. The anion is stabilized by resonance, and its hybrid structure exhibits negative charges on the carbonyl oxygen and the α carbon. This ambident nucleophile can attack an electrophile via two possible sites: the carbonyl oxygen, known as O-attack, or the α carbon, known as C-attack. The nucleophilic attack via the carbanionic site is preferred. This is due to the...

α-Alkylation of ketones is achieved in the presence of alkyl halides and a base. The reaction proceeds via the formation of an enolate ion followed by nucleophilic substitution. The choice of base employed is essential as it is the key factor in determining the reaction outcome.
The reaction involving bases like EtO− whose conjugate acid EtOH (pKa = 15.9) is stronger than the ketone (pKa = 19.2) results in an equilibrium mixture with higher ketone concentration. As a consequence,...

Aldehydes and ketones are prepared from alcohols, alkenes, and alkynes via different reaction pathways. Alcohols are the most commonly used substrates for synthesizing aldehydes and ketones. The conversion of alcohol to aldehyde, which involves the oxidation process, depends on the class of the alcohol used and the strength of the oxidizing agent. For instance, primary alcohol will form an aldehyde when treated with a weak oxidizing agent; however, it gets over-oxidized to a carboxylic acid in...

Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...

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...