Synthetic Access to Aromatic α-Haloketones

Abstract

α-Haloketones play an essential role in the synthesis of complex N-, S-, O-heterocycles; of which some exhibit a remarkable biological activity. Research further illustrated that α-bromo-, α-chloro-, and α-iodoketones are key precursors for blockbuster pharmacological compounds. Over the past twenty years, substantial advances have been made in the synthesis of these industrially relevant building blocks. Efforts have focused on rendering the synthetic protocols greener, more effective and versatile. In this survey, we summarised and thoroughly evaluated the progress of the field, established in the past two decades, in terms of generality, efficacy and sustainability.

The Application of Dibromohydantoin in Chemical Experiment Pedagogy

“…Liquid bromine and N-bromosuccinimide (NBS) are commonly employed as brominating agents. 8,9 Liquid bromine exhibits certain drawbacks, including volatility, high toxicity, strong corrosiveness, and limited reaction selectivity. In comparison to liquid bromine, NBS offers advantages, such as reduced corrosiveness and enhanced safety.…”

“…Presently, the Journal of Chemical Education has documented various bromination reactions encompassing aromatic rings, olefin, and benzyl groups. − However, there is a lack of teaching experiments reporting on the bromination reaction at the α-carbon of carbonyl compounds, primarily due to the absence of safe and environmentally friendly bromination reagents. Liquid bromine and N -bromosuccinimide (NBS) are commonly employed as brominating agents. , Liquid bromine exhibits certain drawbacks, including volatility, high toxicity, strong corrosiveness, and limited reaction selectivity. In comparison to liquid bromine, NBS offers advantages, such as reduced corrosiveness and enhanced safety.…”

Rapid and General Access to α-Haloketones Using Quaternary Ammonium Salts as Halogen Sources

“…α-Halogenated ketones are unique structural units found in natural products and are valuable synthetic intermediates for functional heterocycle molecules preparation. − A significant body of work has been dedicated to the design and development of new synthetic protocols to access haloketones, and most of these processes have been reviewed in the literature. − The major protocols include direct α-halogenation of aryl ketones, oxyhalogenation of hydrocarbons or secondary alcohols, and Friedel–Crafts acylation of corresponding aromatic hydrocarbons with haloacetyl halides. − . Importantly, the commonly used halogenating agents are halogens and HX or N-haloamides.…”

CuCl2‐Catalyzed α‐Chloroketonation of Aromatic Alkenes via Visible‐Light‐Induced LMCT

“…[1] Commonly used α-haloketonation synthetic strategies involving the thermal process include the direct halogenation of ketones, [2] the oxdative halogenation of alcohols, [3] alkynes [4] as well as electron-rich olefins, [5] and miscellaneous routes. [6] In addition, the electrochemical transition metalcatalyzed difunctionalization of alkenes realized oxychlorination of styrenes. [7] Recently, distinguishing from traditional thermochemistry and organic electrochemistry, visible light-driven transition metal catalysis as a new paradigm attracts considerable attention.…”

“…α ‐Haloketones, especially aromatic α ‐chloroketones, are fundamental building blocks in natural products and drug molecules, such as Merochlorin A, Merochlorin B and Napyradiomycin B1 (Figure 1). [1] Commonly used α ‐haloketonation synthetic strategies involving the thermal process include the direct halogenation of ketones, [2] the oxdative halogenation of alcohols, [3] alkynes [4] as well as electron‐rich olefins, [5] and miscellaneous routes [6] . In addition, the electrochemical transition metal‐catalyzed difunctionalization of alkenes realized oxychlorination of styrenes [7] .…”