Practical Synthesis of 2‐Arylacetic Acid Esters via Palladium‐ Catalyzed Dealkoxycarbonylative Coupling of Malonates with Aryl Halides

Abstract

A new palladium-based system was developed that catalyzes the coupling of aryl halides with diethyl malonates in the presence of mild bases. In the course of the reaction, the intermediately formed diethyl arylmalonate is directly converted into the arylacetic acid ester via liberation of carbon dioxide and an alkanol. This cross-coupling/dealkoxycarbonylation process provides an efficient and high-yielding synthetic entry to diversely functionalized arylacetic acid esters. Two complementary protocols were developed, one of which is optimal for electron-rich, the other for electron-poor aryl halides. Both make use of low loadings of palladium (0) (0.5 mol%)/tri-tert-butylphosphonium tetrafluoroborate (1.1 mol%) as the catalyst and diethyl malonate as the reaction solvent. The new procedures are particularly effective for sterically hindered substrates.

Chlorotrimethylsilane and Sodium Iodide: A Useful Combination for the Regioselective Deoxygenation of Arylalkyl‐α‐Diketones

“…[9] Ketones 4a, [15] 4b, [16] 4p [17] and 4t [18] are known products and their spectroscopic data are in agreement with literature. 9a, [19] 9b, [20] 9c, [21] 10b [22] are known products and their spectroscopic data are in agreement with literature.…”

Kinetic Studies on the Palladium(II)‐Catalyzed Oxidative Cross‐Coupling of Thiophenes with Arylboron Compounds and Their Mechanistic Implications

“…Following a procedure by Gooßen et al.,32 a Schlenk tube with a Teflon screw cap was charged with Pd(dba) 2 (92.0 mg, 160 μmol, 0.02 equiv), P( t Bu) 3 ⋅ HBF 4 (102 mg, 350 μmol, 0.044 equiv), and K 2 CO 3 (2.21 g, 16.0 mmol, 2.0 equiv). The reaction vessel was evacuated and backfilled with argon three times.…”

“…The combined organic layers were dried over MgSO 4 ,f iltered, and concentrated in vacuo. After purification by flash column chromatography (Ø = 7.0 cm, l = 15 cm, pentane), product 4 was obtained as ac olorless liquid (3.35 g, 20.4 mmol, 99 % Diethyl 2-(4-deuteriothiophen-3-yl)malonate (5) Following ap rocedure by Gooßen et al, [32] aS chlenk tube with aT eflon screw cap was charged with Pd(dba) 2 (92.0 mg, 160 mmol, 0.02 equiv), P(tBu) 3 ·HBF 4 (102 mg, 350 mmol, 0.044 equiv), and K 2 CO 3 (2. 21 g, 16.0 mmol, 2.0 equiv).…”

Methods for Arylethylation of Amines and Heteroarenes

“…44 Arylacetic acids with complex substitution patterns often need to be prepared from common aromatic building blocks in multistep syntheses. 45 In a related approach, aromatic amines were arylethylated in high yields in one step by treatment with (substituted) arylacetic acids under catalytic hydrogenation (60 bar H 2 , 160 °C) in the presence of catalytic amounts of Ru(acac) 3 , Triphos, and triflimide (Scheme 7). 46 Aniline has been converted into its N-phenethyl derivative with methyl phenylacetate by following the same procedure; furthermore, numerous other aliphatic and aromatic amines have been N-alkylated with other methyl esters.…”