Dowd–Beckwith ring-expansion reaction

Dowd–Beckwith ring-expansion reaction is a significant chemical reaction that involves the expansion of cyclic ketones to larger ring ketones under the influence of peroxides. This reaction is named after Charles N. Dowd and William S. Beckwith, who first reported it in the 1980s. The Dowd–Beckwith ring-expansion reaction is notable for its ability to efficiently increase ring size while maintaining the integrity of the molecular framework, making it a valuable tool in synthetic organic chemistry, particularly in the synthesis of complex natural products and pharmaceuticals.

Mechanism

The mechanism of the Dowd–Beckwith ring-expansion reaction involves several key steps. Initially, a cyclic ketone is treated with a peroxide, such as m-chloroperbenzoic acid (mCPBA), leading to the formation of a highly reactive intermediate known as a peroxycarbenium ion. This intermediate then undergoes a ring expansion to form a larger cyclic ketone. The process is facilitated by the presence of a suitable leaving group, which can vary depending on the specific substrates and conditions employed.

Applications

The Dowd–Beckwith ring-expansion reaction has found widespread application in the synthesis of a variety of complex organic molecules. Its ability to cleanly increase ring size makes it particularly useful in the construction of macrocyclic compounds, which are a class of molecules of interest in drug discovery and material science. Additionally, the reaction has been employed in the total synthesis of natural products, where the efficient and selective formation of larger ring systems is often required.

Variants

Several variants of the Dowd–Beckwith ring-expansion reaction have been developed to expand its scope and applicability. These include modifications to the reaction conditions, such as the use of different peroxides or catalysts, as well as the development of enantioselective versions of the reaction. These advancements have further enhanced the utility of the Dowd–Beckwith ring-expansion reaction in organic synthesis.

Limitations

Despite its many advantages, the Dowd–Beckwith ring-expansion reaction does have some limitations. The requirement for a suitable leaving group can restrict the range of substrates that can be employed. Additionally, the reaction conditions can sometimes lead to side reactions or decomposition of sensitive substrates. Researchers continue to explore modifications and alternatives to overcome these challenges and expand the reaction's utility.

See Also

• Organic synthesis
• Ring expansion
• Peroxide
• Cyclic ketone
• Macrocycle