Department of Chemistry, Indian Institute of Technology Madras, Chennai, 600036, India.
Chemistry. 2020 Jun 5;26(32):7145-7175. doi: 10.1002/chem.201905475. Epub 2020 Apr 9.
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.
α,α-二卤羰基部分是一个双功能系统，具有 1,2-二卤代烃和羰基碳。由于其化学和代谢稳定性以及亲脂性，它是药物化学中的一种重要支架。它们还存在于许多结构不同的天然产物中，并且它们制造的大多数结构已经在医学上使用。除了在药物化学中的重要用途外，α,α-二卤羰基基团还被用作开发新型合成策略的关键构建块，并用作全合成中的中间体。除了氧化、还原和 C-C 键形成等传统转化外，最近还开发了几种新的和非经典反应。本综述简要描述了它们的合成方法，并详细讨论了利用α,α-二卤代酮作为合成砌块发现和开发新反应的努力。我们展示了它们作为合成具有医学和材料重要性以及天然产物的多环系统的关键官能团的用途。
