Synthesis of Indoles through Larock Annulation: Recent Advances

Abstract

The synthesis of indoles through Larock annulation has undergone significant advancements in recent years, marking a renaissance in the field of heterocyclic chemistry. This review paper encapsulates the strides made by highlighting the innovative methodologies that have emerged, the challenges faced, and the potential future directions of this research area. The Larock annulation, traditionally reliant on palladium catalysis, has seen shifts towards more sustainable and economical approaches, such as nickel catalysis, which promises to alleviate some of the environmental and safety concerns associated with the process. Despite its versatility, the reaction faces limitations in substrate scope due to steric and electronic factors, and economic and scalability issues remain a challenge for industrial applications. Looking forward, this review discussed emerging trends such as regioselective syntheses and the expansion of substrate scope, which are likely to drive further research and innovation. The review concluded by reflecting on the impact of the Larock indole synthesis within the broader context of organic chemistry, underscoring its potential to inspire new synthetic strategies and contribute to the advancement of medicinal chemistry.