17016-20-5Relevant academic research and scientific papers
Cascade Reductive Friedel-Crafts Alkylation Catalyzed by Robust Iridium(III) Hydride Complexes Containing a Protic Triazolylidene Ligand
Albrecht, Martin,Alshakova, Iryna D.
, p. 8999 - 9007 (2021/07/31)
The synthesis of complex molecules like active pharmaceutical ingredients typically requires multiple single-step reactions, in series or in a modular fashion, with laborious purification and potentially unstable intermediates. Cascade processes offer attractive synthetic remediation as they reduce time, energy, and waste associated with multistep syntheses. For example, triarylmethanes are traditionally prepared via several synthetic steps, and only a handful of cascade routes are known with limitations due to high catalyst loadings. Here, we present an expedient catalytic cascade process to produce triarylmethanes. For this purpose, we have developed a bifunctional iridium system as the efficient catalyst to build heterotriaryl synthons via reductive Friedel-Crafts alkylation from ketones, arenes, and hydrogen. The catalytically active species were generated in situ from a robust triazolyl iridium(III) hydride complex and acid and is composed of a metal-bound hydride and a proximal ligand-bound proton for reversible dihydrogen release. These complexes catalyze the direct hydrogenation of ketones at slow rates followed by dehydration. Appropriate adjustment of the conditions successfully intercepts this dehydration and leads instead to efficient C-C coupling and Friedel-Crafts alkylation. The scope of this cascade process includes a variety of carbonyl substrates such as aldehydes, (alkyl)(aryl)ketones, and diaryl ketones as precursor electrophiles with arenes and heteroarenes for Friedel-Crafts coupling. The reported method has been validated in a swift one-step synthesis of the core structure of a potent antibacterial agent. Excellent yields and exquisite selectivities were achieved for this cascade process with unprecedentedly low iridium loadings (0.02 mol %). Moreover, the catalytic activity of the protic system is significantly higher than that of an N-methylated analogue, confirming the benefit of the Ir-H/N-H hydride-proton system for high catalytic performance.
Synthesis of Triarylmethanes via Palladium-Catalyzed Suzuki-Miyaura Reactions of Diarylmethyl Esters
Dardir, Amira H.,Casademont-Reig, Irene,Balcells, David,Ellefsen, Jonathan D.,Espinosa, Matthew R.,Hazari, Nilay,Smith, Nicholas E.
, p. 2332 - 2344 (2021/06/28)
The synthesis of triarylmethanes via Pd-catalyzed Suzuki-Miyaura reactions between diarylmethyl 2,3,4,5,6-pentafluorobenzoates and aryl boronic acids is described. The system operates under mild conditions and has a broad substrate scope, including the coupling of diphenylmethanol derivatives that do not contain extended aromatic substituents. This is significant as these substrates, which result in the types of triarylmethane products that are prevalent in pharmaceuticals, have not previously been compatible with systems for diarylmethyl ester coupling. Furthermore, the reaction can be performed stereospecifically to generate stereoinverted products. On the basis of DFT calculations, it is proposed that the oxidative addition of the diarylmethyl 2,3,4,5,6-pentafluorobenzoate substrate occurs via an SN2 pathway, which results in the inverted products. Mechanistic studies indicate that oxidative addition of the diarylmethyl 2,3,4,5,6-pentafluorobenzoate substrates to (IPr)Pd(0) results in the selective cleavage of the O-C(benzyl) bond in part because of a stabilizing η3-interaction between the benzyl ligand and Pd. This is in contrast to previously described Pd-catalyzed Suzuki-Miyaura reactions involving phenyl esters, which involve selective cleavage of the C(acyl)-O bond, because there is no stabilizing η3-interaction. It is anticipated that this fundamental knowledge will aid the development of new catalytic systems, which use esters as electrophiles in cross-coupling reactions.
Synthesis of Triarylmethanes via Palladium-Catalyzed Suzuki Coupling of Trimethylammonium Salts and Arylboronic Acids
Zhang, Zhenming,Wang, Hui,Qiu, Nianli,Kong, Yujing,Zeng, Wenjuan,Zhang, Yongquan,Zhao, Junfeng
, p. 8710 - 8715 (2018/07/21)
An efficient palladium-catalyzed Suzuki coupling of 1,1-diarylmethyl-trimethylammonium triflates with arylboronic acids is reported. This reaction offers a novel approach to triarylmethane derivatives in good to excellent yields with the palladium-catalyzed C-N bond cleavage as the key feature. Broad substrate scope regarding both reaction partners are observed. Moreover, reactive functional groups such as vinyl and formyl groups are conserved in this transformation.
Benzylic Phosphates in Friedel-Crafts Reactions with Activated and Unactivated Arenes: Access to Polyarylated Alkanes
Pallikonda, Gangaram,Chakravarty, Manab
supporting information, p. 2135 - 2142 (2016/03/15)
Easily reachable electron-poor/rich primary and secondary benzylic phosphates are suitably used as substrates for Friedel-Crafts benzylation reactions with only 1.2 equiv activated/deactivated arenes (no additional solvent) to access structurally and electronically diverse polyarylated alkanes with excellent yields and selectivities at room temperature. Specifically, diversely substituted di/triarylmethanes are generated within 2-30 min using this approach. A wide number of electron-poor polyarylated alkanes are easily accomplished through this route by just tuning the phosphates.
Benzylation of arenes with benzyl halides synergistically promoted by in situ generated superacid boron trifluoride monohydrate and tetrahaloboric acid
Huang, Ruofeng,Zhang, Xiaohui,Pan, Jing,Li, Jiaqiang,Shen, Hang,Ling, Xuege,Xiong, Yan
supporting information, p. 1540 - 1546 (2015/03/04)
To examine the assembly methodology of diarylmethanes, a benzylation of (hetero)arenes with benzyl halides has been developed and various diarylmethanes were furnished with yields of up to 98% and regioselectivities of up to >99%. The complexation of the by-product halogen hydride with BF3·OEt2 generated the Bronsted acid BF3·HX (HBF3X, X=Cl or Br) in situ to synergistically promote the benzylation.
LDA-Mediated Synthesis of Triarylmethanes by Arylation of Diarylmethanes with Fluoroarenes at Room Temperature
Ji, Xinfei,Huang, Tao,Wu, Wei,Liang, Fang,Cao, Song
supporting information, p. 5096 - 5099 (2015/11/03)
A practical and convenient approach for the secondary C(sp3)-H arylation of diarylmethanes with various fluoroarenes is described. The reaction proceeds smoothly in the presence of LDA (lithium diisopropylamide) at room temperature and affords triarylmethanes in moderate to high yields.
Simple Method for sp2-sp3 and sp3-sp3 Carbon-Carbon Bond Activation in 2-Substituted 1,3-Diketones
Aoyama, Tadashi,Hayakawa, Mamiko,Kubota, Sho,Ogawa, Sumire,Nakajima, Erika,Mitsuyama, Emi,Iwabuchi, Taku,Kaneko, Haruki,Obara, Rina,Takido, Toshio,Kodomari, Mitsuo,Ouchi, Akihiko
, p. 2945 - 2956 (2015/09/28)
Simple and efficient methods were developed for sp2-sp3 and sp3-sp3 C-C bond-activation reactions of 2-substituted 1,3-diketones. 3-Substituted 3-bromopentane-2,4-diones were deacylated in the presence of an aromatic compound and a silica gel supported Bronsted acid containing sulfonic groups. The carbocation formed by cleavage of the sp3-sp3 C-C bond of the dione alkylated the aromatic compound.
Superacid BF3-H2O promoted benzylation of arenes with benzyl alcohols and acetates initiated by trace water
Zhang, Shuting,Zhang, Xiaohui,Ling, Xuege,He, Chao,Huang, Ruofeng,Pan, Jing,Li, Jiaqiang,Xiong, Yan
, p. 30768 - 30774 (2014/08/05)
A convenient procedure employing simple starting materials benzyl alcohols and acetates as the benzyl donors to assemble a series of diarylalkanes through benzylation of arenes using in situ prepared superacid BF3-H 2O as an efficient promoter has been developed. The beneficial role of water in the reaction has been clarified with combination of control experiments and 11B NMR analysis. This reaction is a self-promoted model, which is triggered by the trace of water and continuously promoted by self released by-product water (or carboxylic acid). A wide range of substrates are investigated and the moderate to excellent yields and the good regioselectivities for secondary benzyl alcohols as well as arenes bearing electron-withdrawing groups have been achieved. As a result, moisture in the reaction system has been utilized as an efficient initiator in all benzylation cases.
Benzylation of arenes with benzyl ethers promoted by the in situ prepared superacid BF3-H2O
Li, Yu,Xiong, Yan,Li, Xueming,Ling, Xuege,Huang, Ruofeng,Zhang, Xiaohui,Yang, Jianchun
, p. 2976 - 2981 (2014/06/10)
An efficient and environmentally friendly benzylation of arenes with benzyl ethers as benzyl donors using BF3-Et2O to generate in situ the superacid BF3-H2O as an efficient promotor has been described. A wide variety of functional groups have been investigated and found to be compatible to give the desired diarylmethanes in yields of up to 99%. The crucial role of the moisture content in this transformation has been demonstrated by detailed investigations. This journal is the Partner Organisations 2014.
Modular synthesis of triarylmethanes through palladium-catalyzed sequential arylation of methyl phenyl sulfone
Nambo, Masakazu,Crudden, Cathleen M.
, p. 742 - 746 (2014/01/23)
Triarylmethanes, which are valuable structures in materials, sensing and pharmaceuticals, have been synthesized starting from methyl phenyl sulfone as an inexpensive and readily available template. The three aryl groups were installed through two sequential palladium-catalyzed C-H arylation reactions, followed by an arylative desulfonation. This method provides a new synthetic approach to multisubstituted triarylmethanes using readily available haloarenes and aryl boronic acids, and is also valuable for the preparation of unexplored triarylmethane-based materials and pharmaceuticals. Unsymmetric triarylmethanes have been synthesized starting from methyl phenyl sulfone as an inexpensive and readily available template. The three aryl groups were installed through two sequential palladium-catalyzed C-H arylation reactions, followed by an arylative desulfonation. Copyright
