Background:
Due to the ubiquitous nature of the ketone functionality, it is considered an
important functional group in organic chemistry. Hence, the synthesis of ketones from readily available
starting materials is an important chemical transformation in organic synthesis. Consequently, several
research efforts have been reported in the literature for the transformation of carboxylic acids to ketones
in a one-pot synthesis. However, some of the procedures have limitations, such as long reaction
times, harsh reaction conditions, and usage of expensive metal catalysts. Thus, a simple and convenient
one-pot conversion of carboxylic acids to ketones remains desirable.
Objective:
We intended to develop a simple and convenient one-pot methodology for the synthesis of
ketones from carboxylic acids. Our objective was to build up a carboxylic acid-based chemical template
where various types of organometallic reagents can interact to produce the desired ketone.
Methods:
In this procedure, a carboxylic acid was converted to a mixed anhydride using mesyl chloride
in the presence of a base. This mixed anhydride was then reacted with a suitable organometallic reagent
at -20°C to obtain the desired ketone. The reaction was performed in a one-pot fashion.
Results:
Under the optimized reaction conditions, various aromatic and heteroaromatic carboxylic acids
were converted to the corresponding ketones using organolithium and organomagnesium reagents
with short reaction times. Moderate to good yields of the desired ketones were observed in many of
these transformations.
Conclusion:
A simple and convenient one-pot method for the conversion of carboxylic acids to ketones
has been reported. Specifically, various aromatic and `heteroaromatic carboxylic acids have been converted
to the corresponding ketones in moderate to good yields. Organomagnesium and organolithium reagents
were used as nucleophiles for this reaction.
Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence
