Synthesis of α-Bromoketones

Recent Literature

A general, rapid, and scalable method for the preparation of α-halogenated ketones using N-alkenoxypyridinium salts as substrates and quaternary ammonium salts as halogen sources offers mild reaction conditions, excellent functional group tolerance, and a wide substrate scope.
N. Wu, M. Jiang, A. Cao, L. Huang, X. Bo, Z. Xu, J. Org. Chem., 2023, 88, 17368-17380.

1-Arylethanones and related compounds are rapidly brominated in dioxane with the H₂O₂-HBr aq system, resulting in the replacement of two hydrogen atoms in the methyl group with bromine. The reaction is also accompanied by bromination of the aromatic ring provided that the latter contains electron-donating substituents.
A. O. Terent'ev, S. V. Khodykin, I. B. Krylov, Y. N. Ogibin, G. I. Nikishin, Synthesis, 2006, 1087-1092.

Selective oxyhalogenations of alkynes were achieved in water under very mild conditions in the presence of inexpensive halogenating reagents, such as N-bromosuccinimide and N-chlorosuccinimde, and FI-750-M as amphiphile. No halogenation at the aromatic rings was detected. Reaction medium and catalyst can be recycled.
L. Finck, J. Brals, B. Pavuluri, F. Gallou, S. Handa, J. Org. Chem., 2018, 83, 7366-7372.

An electrochemical oxydihalogenation of alkynes enables the preparation of α,α-dihaloketones using CHCl₃, CH₂Cl₂, ClCH₂CH₂Cl, and CH₂Br₂ as the halogen source at room temperature.
X. Meng, Y. Zhang, J. Luo, F. Wang, X. Cao, S. Huang, Org. Lett., 2020, 22, 1169-1174.

The combination of dimethyl sulfoxide, HCl, and HBr enables a mild, efficient, and practical geminal heterodihalogenation of methyl ketones. This convenient method might be useful for the assembly of bromochloromethyl groups in drug discovery.
J.-f. Zhou, D.-m. Tang, M. Bian, Synlett, 2020, 31, 1430-1434.

Utilizing the full potential of IBX, a mild, selective, and facile method enables a direct conversion of olefins into the corresponding α-bromo ketones in the presence of 1.1 equivalents each of o-iodoxybenzoic acid and tetraethylammonium bromide.
S. S. Deshmukh, K. H. Chaudhari, K. G. Akamanchi, Synlett, 2011, 81-83.

A triphenylphosphine oxide catalyzed reductive halogenation of an α,β-unsaturated ketone with trichlorosilane as the reducing reagent and an N-halosuccinimide as the electrophilic halogen source enables a selective synthesis of unsymmetrical α-haloketones.
Z. Lao, H. Zhang, P. H. Toy, Org. Lett., 2019, 21, 8149-8152.

HTIB mediates an oxidative transposition of vinyl halides to provide α-halo ketones as useful and polyvalent synthetic precursors. Insights into the mechanism and an enantioselective transformation are reported too.
A. Jobin-Des Lauriers, C. Y. Legault, Org. Lett., 2016, 18, 108-111.

A very rapid and efficient method enables a one-pot synthesis of α,α-dibromoalkanones and β-bromoenol alkanoates directly from alkynes using N,N-dibromo-p-toluenesulfonamide. The protocol offers ambient temperature, high regioselectivity, operational simplicity, and metal- and catalyst-free conditions.
R. Chawla, A. K. Singh, L. D. S. Yadav, Synlett, 2013, 24, 1558-1562.

Efficient oxidative α-halogenation of 1,3-dicarbonyl compounds has been achieved by employing a system comprising of sub-stoichiometric amounts of TiX₄ (X = Cl, Br) in the presence of environmentally benign hydrogen peroxide (H₂O₂) or peracetic acid (MeCO₃H) as the oxidants. The end point of the reaction is accompanied by a sharp colour change.
R. Akula, M. J. Galligan, H. Ibrahim, Synthesis, 2011, 347-351.

Active methylene compounds can be chemoselectively brominated in high yields using potassium bromide, hydrochloric acid, and hydrogen peroxide at room temperature.
M. Kirihara, S. Ogawa, T. Noguchi, K. Okubo, Y. Monma, I. Shimizu, R. Shimosaki, A. Hatano, Y. Hirai, Synlett, 2006, 2287-2289.

1,3-keto esters and 1,3-diketones have been effectively and regioselectively α-monobrominated using bromodimethylsulfonium bromide as reagent.
A. T. Khan, M. A. Ali, P. Goswami, L. H. Choudhury, J. Org. Chem., 2006, 71, 8961-8963.

An efficient one-pot transformation of β-hydroxycarbonyl compounds to α-brominated 1,3-dicarbonyl compounds is achieved with MoO₂Cl₂ in the presence of N-bromosuccinimide. All the reactions were carried out under mild conditions and provide good yields. No bromination occurs at benzylic and allylic positions.
K. Jeyakumar, D. K. Chand, Synthesis, 2009, 306-310.

K. Jeyakumar, D. K. Chand, Synthesis, 2009, 306-310.

A mild and rapid formal electrophilic α-azidation of 1,3-dicarbonyl compounds using commercially available Bu₄NN₃ as the azide source is mediated by (diacetoxyiodo)benzene. The reaction conditions are Bäcklund to the ones employed in analogous halogenations with Et₄NX (X = Cl, Br, I).
M. J. Galligan, R. Akula, H. Ibrahim, Org. Lett., 2014, 16, 600-603.

Poly{[4-(hydroxy)(tosyloxy)iodo]styrene} was efficient in the halotosyloxylation reaction of alkynes with iodine or NBS or NCS. The polymer reagent could be regenerated and reused.
J.-M. Chen, X. Huang, Synthesis, 2004, 1557-1558.

Chiral N,N'-dioxide/Fe(OTf)₂ complexes catalyze an unprecedented highly diastereo- and enantioselective bromoazidation of α,β-unsaturated ketones. An array of aryl, heteroaryl, and alkyl substituted α,β-unsaturated ketones were transformed to the corresponding α-bromo-β-azido ketones in high yields with excellent diastereo- and enantioselectivities. The catalytic system was also applicable for chloroazidations and iodoazidations.
P. Zhou, L. Lin, L. Chen, X. Zhong, X. Liu, X. Feng, J. Am. Chem. Soc., 2017, 139, 13414-13419.

Related

Sodium benzene sulfinate catalyzed a visible-light-driven aerobic oxidative cleavage of olefins to provide the corresponding aldehydes and ketones under transition-metal-free conditions. Notably, α-halo-substituted styrenes proceeded with photoinduced oxidation to finally afford α-halo-acetophenones with halogen migration.
Y.-X. Chen, J.-T. He, M.-C. Wu, Z.-L. Liu, K. Tang, P.-J. Xia, K. Chen, H.-Y. Xiang, X.-Q. Chen, H. Yang, Org. Lett., 2022, 24, 3920-3925.

Au-catalyzed hydration of haloalkynes enables an atom-economical synthesis of a wide range of α-halomethyl ketones as an alternative to conventional α-halogenation of ketones. Other outstanding features include excellent yields from both alkyl- and aryl-substituted haloalkynes and wide functional group tolerance.
L. Xie, Y. Wu, W. Yi, L. Zhu, J. Xiang, W. He, J. Org. Chem., 2013, 78, 9190-9191.