The α,α‐dihalocarbonyl moiety is a bifunctional system with a gem‐dihalocarbon and a carbonyl carbon in 1,2‐fashion. This is one of the privileged scaffolds in medicinal chemistry due to its chemical and metabolic stability and lipophilicity. They have also been found in numerous structurally divergent natural products and most of their fabricated structures have already been in medicinal use. Apart from their important use in medicinal chemistry, the α,α‐dihalocarbonyl groups have been employed as key building blocks for the development of novel synthetic strategies and utilized as intermediates in total synthesis. In addition to the traditional transformations such as oxidations, reductions, and C−C bond formations, recently several new and non‐classical reactions have also been developed. This review provides short description of existing methods for their synthesis and detailed discussion on the efforts for the discovery and development of new reactions by employing α,α‐dihaloketones as synthetic building blocks. We have presented their use as key functional groups for the synthesis of polycyclic systems of medicinal and material importance and natural products.

A Regioselective and efficient synthesis of α,α‐diiodo‐α′‐acetoxyketones as well as α,α‐dibromo‐α′ ‐acetoxyketones has been achieved from the propargylic acetates and N‐iodo(bromo)succinimides in the absence of any added promoters. This transformation is very general and shown compatibility for all structural types of propargylic acetates with terminal alkyne unit, such as tertiary‐ (aryl‐aryl; aryl‐alkyl; alkyl‐alkyl), secondary‐ (aryl; alkyl), primary‐; and hence provided access to structurally divergent and highly important halogenated building blocks.

The Lewis base character of the greenest reagent water has been explored with regard to its nucleophilic property for an organic transformation. Utilizing this concept, a new strategy for the highly controlled and selective mono‐dehalogenation of α,α‐dihalo ketones has been discovered and is reported in this contribution. Extending this concept, the first direct conversion of propargylic acetates to the corresponding α‐iodo ketones via α,α‐dihalo ketones has also been efficiently achieved under metal‐free conditions. During the latter process, water has been concurrently employed as a nucleophile and a Lewis base. This may be the first report of the employment of this type of dual reactivity of water in the context of organic synthesis. Control experiments support the involvement of the enolate as an intermediate during the monodehalogneation process.magnified image

What is the most significant result of this study?The reported study uncovers an ovel reactivity of propargylic acetates under metal-free conditions, and shows an ew class of a,adihalo-b-acetoxyketone intermediates as well as mechanistic pathway.T he key player here is the water,w hich acts as aL ewis base in contrast to traditional nucleophilicity.

Invited for the cover of this issue are Santu Sadhukhan and Beeraiah Baire at the Indian Institute of Technology Madras. Read the full text of the article at 10.1002/chem.201901856.