Palladium-catalyzed regioselective arylation of 1,1,3-triaryl-2-azaallyl anions with aryl chlorides.
ABSTRACT: A regioselective arylation of 1,1,3-triaryl-2-azaallyl anions with aryl chlorides is described. The palladium-NIXANTPHOS-based catalyst affords diarylmethylamine derivatives in good yield and without product isomerization. A gram scale sequential one-pot ketimine synthesis/arylation protocol was also developed.
Project description:Diarylmethylamines are of great interest due to their prevalence in pharmaceutical chemistry. As a result, new methods for their synthesis are in demand. Herein, we report a versatile protocol for the synthesis of diarylmethylamine derivatives involving palladium-catalyzed arylation of in situ generated 2-azaallyl anion intermediates. The 2-azaallyl anions are generated by reversible deprotonation of readily available aldimine and ketimine precursors. Importantly, the arylated aldimine and ketimine products do not undergo isomerization under the reaction conditions. Scale-up of the arylation and hydrolysis of the resulting products to furnish diarylmethylamines were also successfully performed.
Project description:An umpolung synthesis of diarylmethylamine derivatives is presented. This reaction entails a Pd catalyzed arylation of 1,3-diaryl-2-azaallyl anions, in situ generated from N-benzyl aldimines. A Pd(NIXANTPHOS)-based catalyst together with hindered silylamide bases enabled the coupling of aldimines with aryl bromides in good to excellent yields without product isomerization. Moreover, regioselectivity in the arylation of unsymmetrical 1,3-diaryl-2-azaallyl anions was studied. This method is suitable for a gram scale synthesis of diarylmethylamine derivatives at room temperature without use of a glovebox.
Project description:Tetraarylmethane derivatives are desirable for a variety of applications, but difficult to access with modern C-C bond-forming reactions. Here we report a straightforward method for palladium-catalysed arylation of aryl(heteroaryl)methanes and diaryl(heteroaryl)methanes with aryl chlorides. This reaction enables introduction of various aryl groups to construct triaryl(heteroaryl)methanes via a C-H functionalization in good to excellent yield, and represents the first step towards a general transition metal catalysed synthesis of tetraarylmethanes.
Project description:Although the past 15 years have witnessed the development of sterically bulky and electron-rich alkylphosphine ligands for palladium-catalyzed cross-couplings with aryl chlorides, examples of palladium catalysts based on either triarylphosphine or bidentate phosphine ligands for efficient room temperature cross-coupling reactions with unactivated aryl chlorides are rare. Herein we report a palladium catalyst based on NiXantphos, a deprotonatable chelating aryldiphosphine ligand, to oxidatively add unactivated aryl chlorides at room temperature. Surprisingly, comparison of an extensive array of ligands revealed that under the basic reaction conditions the resultant heterobimetallic Pd-NiXantphos catalyst system outperformed all the other mono- and bidentate ligands in a deprotonative cross-coupling process (DCCP) with aryl chlorides. The DCCP with aryl chlorides affords a variety of triarylmethane products, a class of compounds with various applications and interesting biological activity. Additionally, the DCCP exhibits remarkable chemoselectivity in the presence of aryl chloride substrates bearing heteroaryl groups and sensitive functional groups that are known to undergo 1,2-addition, aldol reaction, and O-, N-, enolate-?-, and C(sp(2))-H arylations. The advantages and importance of the Pd-NiXantphos catalyst system outlined herein make it a valuable contribution for applications in Pd-catalyzed arylation reactions with aryl chlorides.
Project description:Polyborylated organic compounds have been emerging as versatile building blocks in chemical synthesis. Here we report a selective cobalt-catalyzed deoxygenative 1,1,3-triborylation reaction of allylic ethers with pinacolborane to prepare 1,1,3-triborylalkane compounds. With naturally abundant and/or synthetic cinnamic methyl ethers as starting materials, we have achieved the synthesis of a variety of 1,1,3-triborylalkanes (25 examples). The synthetic utility of these 1,1,3-triborylalkanes is demonstrated through site-selective allylation, protodeborylation, and consecutive carbon-carbon bond-forming reactions. Mechanistic studies including deuterium-labeling and control experiments suggest that this 1,1,3-triborylation reaction proceeds through initial cobalt-catalyzed deoxygenative borylation of allylic ethers to form allylic boronates followed by cobalt-catalyzed 1,1-diborylation of the resulting allylic boronates.
Project description:2-Amino-1,1,3-tricyanopropene inhibits photosynthetic O(2) evolution, but, unlike 3-(3,4-dichlorophenyl)-1,1-dimethylurea, has little effect on the steady-state fluorescence of chlorophyll. In chloroplasts prepared from spinach leaves and inhibited by 2-amino-1,1,3-tricyanopropene, a 3-(3,4-dichlorophenyl)-1,1-dimethylurea-sensitive photoreduction of ferricyanide may be restored by addition of semicarbazide. It is concluded that 2-amino-1,1,3-tricyanopropene acts at a point close to the photo-oxidation of water.
Project description:A tandem arylation/oxidation of diarylmethanes for the convenient synthesis of unsymmetrical triarylmethanols bearing different aryl and heteroaryl groups is described. A Pd(OAc)2-NiXantphos catalyst system efficiently catalyzed arylation of weakly acidic sp(3)-hybridized C-H bonds of diarylmethanes with aryl bromides, and the arylation products were then oxidized in situ to carbinols by simply opening the reaction flasks to air. The triarylmethanol products were obtained in 35-98% yield.
Project description:The synthesis of four new 1,3,5-triaryl-1,3,5-triazinane-2,4,6-trithione derivatives (thioisocyanurates) and two new partially thionated analogues from the corresponding 1,3,5-triaryl-1,3,5-triazinane-2,4,6-triones (isocyanurates) is reported, together with their spectroscopic properties. DFT calculations and comparison with the corresponding isocyanurates evidence the impact of the oxygen-for-sulfur replacement on the electronic structure and linear optical properties of these heterocycles. A bathochromic shift of the absorption bands and more efficient quenching of the fluorescence was observed.
Project description:The direct arylation of weakly acidic sp3-hybridized C-H bonds via deprotonated cross-coupling processes (DCCP) is a challenge. Herein, a Pd(NIXANTPHOS)-based catalyst for the mono arylation of 4-pyridylmethyl 2-aryl ethers to generate diarylated 4-pyridyl methyl ethers is introduced. Furthermore, under similar conditions, the diarylation of 4-pyridylmethyl ethers with aryl bromides has been developed. These methods enable the synthesis of new pyridine derivatives, which are common in medicinally active compounds and in application in materials science.
Project description:Isoindolinones comprise an important class of medicinally active compounds. Herein we report a straightforward functionalization of the isoindolinones with aryl bromides (22 examples) using a Pd(OAc)2/NIXANTPHOS-based catalyst system. Additionally 3-aryl 3-hydroxy isoindolinone derivatives, which exhibit anti-tumor activity, can be accessed via a tandem reaction. Thus, when the arylation product is exposed to air under basic conditions, in situ oxidation takes place to install the 3-hydroxyl group. Furthermore, a tandem arylation/allylic substitution reaction is advanced in which both the arylation and allylic substitution are catalyzed by the same palladium catalyst. Finally, a tandem arylation/alkylation procedure is presented. These tandem reactions enable the synthesis of a variety of structurally diverse isoindolinone derivatives from common starting materials.