In organic chemistry, the conversion of acid chlorides to ketones can be achieved through a process involving nucleophilic acyl substitution (NAS). Both acid chlorides and esters possess a good leaving group adjacent to the carbonyl, which facilitates this reaction. When organometallic reagents, characterized by a negatively charged alkyl group (R-), react with these compounds, they undergo a two-step mechanism.
Initially, the organometallic reagent attacks the carbonyl carbon, forming a tetrahedral intermediate. This intermediate contains the original alkyl group (R) and the leaving group (OR or Cl). Instead of forming an alcohol through protonation, the leaving group is expelled, resulting in the formation of a ketone. However, the reaction does not stop here, as the remaining carbonyl can undergo a second nucleophilic attack by the organometallic reagent, leading to another tetrahedral intermediate. This results in a disubstituted alcohol, as the same R group has been added twice.
To specifically synthesize ketones without progressing to the alcohol, a Gilman reagent (dialkylcuprate) can be employed. Gilman reagents are less reactive than other organometallics, allowing them to stop after the first nucleophilic addition. In this case, the R- attacks the carbonyl, displacing the leaving group (Cl) and yielding a ketone without further reaction. This selective reactivity is crucial for achieving the desired product without overreacting to form an alcohol.
In summary, while organometallic reagents typically react twice with acid chlorides and esters, leading to disubstituted alcohols, the use of Gilman reagents allows for the efficient formation of ketones by halting the reaction after the first addition. Understanding these mechanisms is essential for effective synthetic strategies in organic chemistry.
