Arylation of diethyl malonate and ethyl cyanoacetate catalyzed by palladium/di-tert-butylneopentylphosphine

Abstract

EtO OEt O O EtO OEt O O Pd(dba) 2 t-Bu 2 P t-Bu Ar EtO CN O Ar ArX EtO CN O Base Br: 20 examples Cl: 8 examples Br: 7 examples © 2015. This manuscript version is made available under the Elsevier user licenseAbstract α-Arylated carbonyl derivatives are important structural motifs in many natural products and pharmaceutically active compounds. Although arylation of simple monocarbonyl compounds is a well-established methodology, metal-catalyzed arylation of β-dicarbonyl derivatives is significantly more challenging. The ability ofβ-dicarbonyl anions to bind to palladium in a κ 2 -O,O mode, rather than the κ 1 -C-bound mode required for bond formation, often results in the deactivation of catalyst systems. The C-bound form of the enolate can be favored through the use of sterically demanding ligands. Herein, we report that the sterically demanding di-tertbutylneopentylphosphine (DTBNpP) ligand in combination with Pd(dba) 2 provides an effective catalyst for the coupling of aryl bromides and chlorides with diethyl malonate. The Pd/DTBNpP system also catalyzes the coupling of aryl bromides with ethyl cyanoacetate.

Air-Stable [(R3P)PdCl2]2Complexes of Neopentylphosphines as Cross-Coupling Precatalysts: Catalytic Application and Mechanism of Catalyst Activation and Deactivation

“…We have had a longstanding interest in the use of neopentyl-substituted phosphines as ligands in cross-coupling reactions. Di -tert -butylneopentylphosphine (DTBNpP) and trineopentylphosphine (TNpP) have been shown to be effective ligands for a variety of C–C and C–heteroatom bond-forming reactions. ,, Like tri- tert- butylphosphine, DTBNpP is rapidly oxidized on exposure to air . Therefore, we sought to develop air-stable complexes that could be used as catalyst precursors in coupling reactions.…”

On the hydrolysis of diethyl 2-(perfluorophenyl)malonate

“…At the same time, diethyl 2-(perfluorophenyl)malonate ( 3 ) is a readily accessible compound. Diethyl 2-phenylmalonate ( 4 ) is usually obtained ( Scheme 1 ) by condensation of ethyl phenylacetate ( 5 ) and diethyl carbonate under basic conditions [ 22 ] because of the low reactivity of bromobenzene in noncatalytic nucleophilic reactions with sodium salts of diethyl malonate ( 6 ) [ 23 – 24 ].…”

Chlorophenols in organic synthesis

“…Sterically demanding ligand -di-tret-butylneopentylphosphin (DtBP) -in combination with Pd(dba) 2 is an effective catalyst for the combination of arylchlorides with diethylmalonate 13. As a result of experiments the compounds 14a (85 %) and 14b (83 %) were obtained [19].…”

“…Стерически требовательный лиганд -ди-трет-бутилнеопентил-фосфин (ДТБНпП) -в комбинации с Pd(dba) 2 является эффективным ката-лизатором для сочетания арилхлори-дов с диэтилмалонатом 13. В результате экспериментов были получены соеди-нения 14a (85 %) и 14b (83 %) [19].…”