Di‐tert‐butylneopentylphosphine (DTBNpP): An Efficient Ligand in the Palladium‐Catalyzed α‐Arylation of Ketones

Abstract

Di‐tert‐butylneopentylphosphine (DTBNpP) and palladium(II) acetate provide an efficient catalytic system for the α‐arylation of ketones. Aryl bromides were coupled with ketones using 0.25–0.5 mol‐% Pd(OAc)2/DTBNpP in toluene at 50 °C, whereas aryl chlorides required a higher catalyst loading (0.5–2.0 mol‐%) and a higher temperature (80 °C). Coupling of 2‐bromophenol with ketones using the Pd/DTBNpP system provides an efficient route for the synthesis of benzofurans.

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

“…In contrast, the more sterically demanding 2-bromoanisole gave only a 29% conversion to product (entry 6).In the arylation of propiophenone with the DTBNpP/Pd system, ortho-substituted aryl halides were tolerated, but low yields were obtained with di-ortho-substituted aryl halides. 15 Switching to the more flexible TNpP ligand provided high yields with di-orthosubstituted aryl bromides. Use of TNpP in the coupling of 2-bromoanisole with diethyl malonate gave minimal conversion to product, however.…”

“…5 Our group has previously reported the use of di-tert-butylneopentylphosphine (DTBNpP), tert-butyldineopentylphosphine (TBDNpP) and trineopentylphosphine (TNpP) in C-C bondforming reactions, 13 amine arylations, 14 and arylation of ketone enolates. 15 Calculated cone angles suggest that DTBNpP is more sterically demanding than tri-tert-butylphosphine (TTBP) and has similar electronic properties. 14a Additional neopentyl groups further increase the calculated cone angle, but also provide additional conformational flexibility.…”

“…As a result, TNpP appears to be effectively less sterically demanding than DTBNpP or TTBP and provides effective catalysts for cross-coupling of highly sterically demanding substrates. 14b, 15 Given the steric and electronic properties of DTBNpP and its successful application in the arylation of ketones, we hypothesized that it might provide an effective ligand for the arylation of dialkyl malonates and other active methylene compounds.…”

Versatile Pyrolytic Synthesis of Fused Polycyclic Heteroaromatic Compounds

“…Direct pyrolysis of this material at 850 °C followed by short-column chromatography to remove Ph 3 PO then afforded an oil which was shown by GCMS and HPLC to contain all twelve expected heterocyclic products as confirmed by comparison with the individually prepared au- We were also interested to investigate formation of partly hydrogenated polycyclic heterocycles by this method and by starting from the 3-phenylpropylphosphonium salt the ylides 80 and 81 were prepared (Scheme 14, Table 1). Pyrolysis of these proceeded cleanly to give the 5,6-dihydro products 82 23 and 83 24 at optimal temperatures of 750 °C and 800 °C respectively.…”

Catalytic α-Arylation of Imines Leading to N-Unprotected Indoles and Azaindoles

“…Discovered concomitantly by Hartwig, Buchwald, and Miura, 9 this process has rapidly evolved and can currently be performed on a wide range of coupling partners in a very efficient manner. 10 The well-known chemistry of carbonyl compounds makes these protocols particularly suitable for further functionalization toward complex molecules: 11 indeed, during the past decade, the application of the α-arylation (or vinylation) of carbonyl derivatives has provided a number of protocols achieving highly substituted heterocyclic moieties such as indole derivatives, 12 benzofurans, 13 isoquinolines, 14 and pyridines 15 (see Scheme 1 ).…”