Reliable and General Method for the Cleavage of α-Arylheteroatom-Substituted Carboxylic Acids

Abstract

Bonds between arylheteroatom moieties and α-carbons of carboxylic acids are efficiently cleft by azide transfer and subsequent Curtius rearrangement. The scope of the one-pot protocol covers differently substituted carboxylic acids and heteroatoms like O, S, Se, and N.

Key words

azides - cleavage - carboxylic acids - arenes - rearrangement

References and Notes

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General Procedure for the Cleavage Sequence
The substrate (0.60 mmol) is dissolved in anhyd toluene (1.5 mL) and anhyd DMF (0.15 mL). After addition of Et₃N (1.01 equiv) and azide-transfer reagent (1.1 equiv, DPPA or DEPA) the mixture was stirred for 30 min at ambient temperature and then brought to reflux for 3 h. Then, KOH solution (0.7 mL, 50 wt% in H₂O), EtOH (1.5 mL), and glycerol (0.8 mL) were added to the reaction mixture before refluxing for 2 h. For workup, the reaction mixture was brought to pH 5 by the addition of a sat. citric acid solution. Subsequently, the aqueous layer was extracted with EtOAc (3 25 mL). The combined organic fractions are washed two times with brine (25 mL), dried over MgSO₄, and concentrated under reduced pressure. Purification was performed by column chromatography.

16

Structural identity was proven by consistent NMR and MS spectra. Additionally, GC was performed for assessment of purity.