Reactions with Halogens
This post is about reactions involving the use of halogenated products in organic chemistry. The post is active and growing, so you can expect more examples to be added over time. Please be sure to come back. The updates will be announced on my instagram account.
Last update 23/06/08.
Alkylation
Chemical reactions involving the exchange of a halogen atom for an alkyl group.
2. For the synthesis of Elmonin.
Alkylation via Li-halogen exchange.
1. For the synthesis of Ubrogepant.
Halogen-metal exchange followed by quenching of the arylmagnesium species with DMF and subsequent reduction to provide the alcohol.
Alpha Halogenation
Reactions where the alpha position of a carbonyl group gains a halogen atom.Â
4. For the synthesis of Asnovolin A.
An iodide handle was installed on the electron-rich vinylogous ester in high yield (84%) using CAN/I2 at 0 °C.
3. For the synthesis of Phomarol.
The substrate was treated with iodine, TMSN3, and pyridine in dichloromethane to generate the iodide.
CCS Chem. 2021, 3, 348. Open access.
2. For the synthesis of Adociaquinone A.
1. For the synthesis of Esaxerenone.
Fluorine
Reactions involving the fluorine atom.
4. For the synthesis of Alpelisib.
Subjecting the picoline analog to Ruppert’s reagent (TMSCF3) in the presence of sodium acetate followed by hydrolytic silyl group removal provided the tertiary alcohol.
3. For the synthesis of Ubrogepant.
Trifluoroethylation was effected under strongly basic conditions to obtain the desired monoalkylated product.
2. For the synthesis of Lascufloxacin.
Treatment with perfluoro-1-octanesulfonyl fluoride, POSF, delivered the chiral fluoride with inversion of stereochemistry.
1. For the synthesis of Bauhinoxepin C.
This compound was fluorinated with Selectfluor to give 4-fluoro-2-methylresorcinol.
Halogenation
13. For the synthesis of Amphidinolide C2.
12. For the synthesis of Relugolix.
Radical bromination conditions gave the benzyl bromide.
11. For the synthesis of 10-hydroxyacutuminine.
10. For the synthesis of Erdafitinib.
Chlorination of 6-bromoquinozaline.
9. For the synthesis of Darolutamide.
The pyrazole was lithiated at C-5 and quenched with bromine to yield bromopyrazole.
8. For the synthesis of Siponimod.
Bromination with DBMH, an alternative to NBS.
7. For the synthesis of Trifarotene.
6. For the synthesis of Cefiderocol.
5. For the synthesis of Spiroindimicin A.
Chem. Sci. 2021, 12, 10388. Open access.
4. For the synthesis of Russujaponol F.
Monoiodination using iodine and Selectfluor.
3. For the synthesis of Peniciketal A.
2. For the synthesis of Lynamicin A.
Chem. Sci. 2021, 12, 13756. Open access.
1. For the synthesis of Codonopiloneolignanin A.
 Bromination of the benzene ring with NBS.
Other Reactions
6. For the synthesis of Bempedoic acid.
The substrate was reacted with 0.5 equivalents of toluenesulfonylmethyl isocyande under basic conditions to facilitate a double alkylation reaction of the iodide to obtain the isonitrile. The isonitrile was then subjected to acidic conditions in isopropyl acetate and pH adjustment to uncover the masked carbonyl group.
5. For the synthesis of Remogliflozin Etabonate.
Chlorination of the benzyl alcohol moiety.
4. For the synthesis of Ubrogepant.
Conversion to the iodide via a Finkelstein reaction.
3. For the synthesis of Voxelotor.
Treatment with thionyl chloride in dichloromethane provided pyridinyl chloride.
2. For the synthesis of Ambiguine G.
J. Am. Chem. Soc. 2021, 143, 10872. Open access.
1. For the synthesis of Alpneumine H.
Chem. Sci. 2021, 12, 4747. Open access.
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