Direct, one-pot sequential reductive alkylation of lactams/amides with Grignard and organolithium reagents through...

Organomagnesium halides, commonly known as Grignard reagents, convert acid halides to tertiary alcohols. The reaction requires two equivalents of the Grignard reagent and proceeds via a ketone intermediate.
Grignard reagents are a source of carbanions and function as nucleophiles. The mechanism begins with the nucleophilic attack by the carbanion at the carbonyl carbon of the acid halide to form a tetrahedral intermediate. Next, the carbonyl group is re-formed, and the halide ion departs,...

Amide reduction with strong reducing agents like lithium aluminum hydride proceeds through a nucleophilic acyl substitution to form amines. Primary, secondary, and tertiary amides yield primary, secondary, and tertiary amines, respectively.
Amide reduction requires two equivalents of the reducing agent, acting as a source of hydride ions. As shown in the figure, the reaction is initiated with a nucleophilic attack by the hydride ion at the carbonyl carbon to form a tetrahedral intermediate.

The reaction of an ester with a Grignard reagent, followed by hydrolysis of the magnesium alkoxide salt in aqueous acid, yields a tertiary alcohol. In the case of formate esters, secondary alcohols are formed.
The reaction requires two equivalents of the Grignard reagent and introduces two identical alkyl groups, derived from the Grignard reagent, bonded to the hydroxyl-bearing carbon of the alcohol.
The reaction follows the typical nucleophilic acyl substitution mechanism. The Grignard...

Carbonyl compounds and primary amines undergo reductive amination first to produce imines, followed by secondary amines in the same reaction mixture, using selective reducing agents like sodium cyanoborohydride or sodium triacetoxyborohydride. Reductive amination produces different degrees of substitution of amines depending on the starting amine substrate.

Lithium dialkyl cuprate, also known as Gilman reagents, selectively reduces acid halides to ketones. The acid chloride is treated with Gilman reagent at −78 °C in the presence of ether solution to produce a ketone in good yield.
As shown below, the mechanism proceeds in two steps. First, one of the alkyl groups of the reagent acts as a nucleophile and attacks the acyl carbon of the acid chloride to form a tetrahedral intermediate. This is followed by the reformation of the carbon–oxygen double...

Nitriles are reduced to amines in the presence of strong reducing agents like lithium aluminum hydride through a typical nucleophilic acyl substitution. The reaction requires two equivalents of the reducing agent. The reducing agent acts as a source of hydride ions.
As shown below, the mechanism involves three steps. Firstly, the hydride ion acting as a nucleophile attacks the nitrile carbon to form an anion. In the second step, a second equivalent of the hydride ion attacks the anion to...