Organic Chemistry Portal

Abstracts

Search:

Synthesis of Alkyl Fluorides and Fluorinated Unnatural Amino Acids via Photochemical Decarboxylation of α-Fluorinated Carboxylic Acids

Álvaro Gutiérrez-Bonet* and Wenbin Liu*

*Process Research & Development, MRL, Merck & Co., Inc., West Point, Pennsylvania 19486, United States, Email: alvaro.gutierrez.bonetmerck.com, wenbin.liumerck.com

A. Gutiérrez-Bonet, W. Liu, Org. Lett., 2023, 25, 483-487.

DOI: 10.1021/acs.orglett.2c04144



see article for more reactions

Abstract

The generation of α-fluoroalkyl or fluorobenzyl radicals from readily available α-fluorocarboxylic acids under mild reaction conditions and their utilization in the Giese-type addition on Michael acceptors and dehydroamino acids provides mono- and difluorinated Michael addition adducts and unnatural fluorinated amino acids.

see article for more examples


proposed mechanism



Decarboxylative Couplings towards Fluorinated Michael Adducts

A 4-dram vial was charged with the corresponding Michael acceptor or dehydroamino acid (1.00 equiv, 0.400 mmol), fluorocarboxylic acid (3.00 equiv, 1.200 mmol), 3,6-Bis(1,1-dimethylethyl)-10-phenyl-9-(2,4,6-trimethylphenyl)-acridinium tetrafluoroborate (Acr-2) (0.05 equiv, 0.020 mmol), and K3PO4 (65.15 wt%, 1.30 equiv, 0.522 mmol). Then, 4.0 mL of anhydrous DCM (0.1 M) were added under nitrogen atmosphere. The mixture was allowed to react at room temperature under blue LED irradiation (450 nm) for 48 h. Next, the mixture was diluted with DCM (5 mL) and NaHCO3 (aq., sat., 3 mL) was added. After stirring for 2 min, the phases were separated. The resulting aqueous phase was extracted two more times with DCM. The combined organic layers were then concentrated in the rotavap. Crude reaction mixture was purified under reverse phase using an automated system (12 g silica gel column, using water (0.1% TFA)/MeCN (0.1% TFA) from 9:1 to 0:1 ratio as eluant). The fractions containing desired product were combined, concentrated in the rotavap, and neutralized by adding 2 mL of NaHCO3 (aq., sat., 3 mL) to remove TFA traces. The mixture was extracted 3 times with DCM (3 mL). Upon drying over MgSO4, the solution was taken to dryness in the rotavap and dried under high vacuum.


Key Words

amino acids, photochemistry


ID: J54-Y2023