Ferric chloride-catalyzed decarboxylative alkylation of β-keto acids with benzylic alcohols

Cuifeng Yang,Haihua Li,Shikai Tian,Chen Shen

doi:10.1007/s11434-012-5140-0

Abstract

β-Keto acids are unstable to heat, acids, and bases, and have rarely been employed as carbon nucleophiles for the formation of carbon-carbon bonds. In this context, an efficient decarboxylative alkylation reaction of β-keto acids with benzylic alcohols has been developed, for the first time, through sequential cleavage of carbon-oxygen and carbon-carbon bonds. In the presence of 10 mol% of ferric chloride, a range of β-keto acids smoothly undergo decarboxylative alkylation with benzylic alcohols to give structurally diverse unsymmetric ketones in moderate to excellent yields and with extremely high regioselectivity. Preliminary mechanistic studies indicate that the reaction proceeds through an SN1 alkylation followed by decarboxylation.

Highlights

In sharp contrast to β-keto esters, β-keto acids have rarely been employed as carbon nucleophiles in the formation of carbon-carbon bonds
A few appropriate conditions have been reported for β-keto acids to undergo decarboxylative carbon-carbon bond-forming reactions with carbon electrophiles such as aldehydes [1−5], imines [6,7], electron-deficient alkenes [8−10], allylic acetates [11], 1,3-diene monoepoxides [12], and N-benzylic sulfonamides [13]
In the course of investigating sp3 carbon-nitrogen bond cleavage [13−20], we recently found that N-benzylic sulfonamides could serve as carbon electrophiles for the decarboxylative alkylation of β-keto acids [13]

Summary

General information

Yang C F, et al Chin Sci Bull July (2012) Vol. No.19 corrected. Alcohols [26,28] and β-keto acids [1,10,29] were prepared according to known procedures, and the rest of chemicals were purchased and used as received. Yang C F, et al Chin Sci Bull July (2012) Vol.. Alcohols [26,28] and β-keto acids [1,10,29] were prepared according to known procedures, and the rest of chemicals were purchased and used as received. The solvents were dried over anhydrous magnesium sulfate prior to use. 1.2 General procedure for the decarboxylative alkylation of β-keto acids with benzylic alcohols. To a solution of benzylic alcohol 2 (0.20 mmol) in 1,2dichloroethane (1.0 mL) at room temperature were added β-keto acid 1 (0.24 mmol) and ferric chloride (3.2 mg, 10 mol%). The resulting mixture was stirred at 60°C for 40 min, and cooled to room temperature. The mixture was purified by column chromatography on silica gel, eluting with petroleum ether/ethyl acetate (20:1), to give compound 3

Characterization data

Results and discussion

Conclusion