Project description:Phenols, anilines, and malonates have been arylated under metal-free conditions with twelve aryl(phenyl)iodonium salts in a systematic chemoselectivity study. A new "anti-ortho effect" has been identified in the arylation of malonates. Several "dummy groups" have been found that give complete chemoselectivity in the transfer of the phenyl moiety, irrespective of the nucleophile. An aryl exchange in the diaryliodonium salts has been observed under certain arylation conditions. DFT calculations have been performed to investigate the reaction mechanism and to elucidate the origins of the observed selectivities. These results are expected to facilitate the design of chiral diaryliodonium salts and the development of catalytic arylation reactions that are based on these sustainable and metal-free reagents.
Project description:A general Cu-catalyzed, regioselective method for the N-3-arylation of hydantoins is described. The protocol utilizes aryl(trimethoxyphenyl)iodonium tosylate as the arylating agent in the presence of triethylamine and a catalytic amount of a simple Cu-salt. The method is compatible with structurally diverse hydantoins and operates well with neutral aryl groups or aryl groups bearing weakly donating/withdrawing elements. It is also applicable for the rapid diversification of pharmaceutically relevant hydantoins.
Project description:A transition metal-free approach for the N-arylation of amino acid derivatives has been developed. Key to this method is the use of unsymmetric diaryliodonium salts with anisyl ligands, which proved important to obtain high chemoselectivity and yields. The scope includes the transfer of both electron deficient, electron rich and sterically hindered aryl groups with a variety of different functional groups. Furthermore, a cyclic diaryliodonium salt was successfully employed in the arylation. The N-arylated products were obtained with retained enantiomeric excess.
Project description:Metal-free N- and O-arylation reactions of pyridin-2-ones as ambident nucleophiles have been achieved with diaryliodonium salts on the basis of base-dependent chemoselectivity. In the presence of N,N-diethylaniline in fluorobenzene, pyridin-2-ones were very selectively converted to N-arylated products in high yields. On the other hand, the O-arylation reactions smoothly proceeded with the use of quinoline in chlorobenzene, leading to high yields and selectivities. In these methods, a variety of pyridin-2-ones in addition to pyridin-4-one and a set of diaryliodonium salts were accepted as suitable reaction partners.
Project description:NOBIN and BINAM derivatives harboring biaryl frameworks are recognized as a class of important atropisomers with versatile applications. Here, we present an efficient synthetic route to access such compounds through copper-catalyzed domino arylation of N-arylhydroxylamines or N-arylhydrazines with diaryliodonium salts and [3,3]-sigmatropic rearrangement. This reaction features mild conditions, good substrate compatibility, and excellent efficiency. The practicality of this protocol was further extended by the synthesis of biaryl amino alcohols.
Project description:A catalytic enantioselective and regiodivergent arylation of alkenes is described. Chiral copper(II)bisoxazoline complexes catalyze the addition of diaryliodonium salts to allylic amides in excellent ee. Moreover, the arylation can be controlled by the electronic nature of the diaryliodonium salt enabling the preparation of nonracemic diaryloxazines or β,β'-diaryl enamides.
Project description:Since the landmark work of Heck, Negishi and Suzuki on Pd-catalyzed crossing coupling reactions, innovative discovery of new reactions forming C-C bonds and constructing functional olefins via nonmetal catalysts remains an imperative area in organic chemistry. Herein, we report a transition-metal-free arylation method of vinyl pinacolboronates with diaryliodonium salts to form C(sp2)-C(sp2) bond and provide trans-arylvinylboronates. The resulting vinylboronates can further react with the remaining aryl iodides (generated from diaryliodonium salts) via Suzuki coupling to afford functional olefins, offering an efficient use of aryliodonium salts. Computational mechanistic studies suggest radical-pair pathway of the diaryliodonium salts promoted by the multi-functional wet carbonate.
Project description:We developed a direct metal-free S-arylation of phosphorothioate diesters using diaryliodonium salts. The method allows for the preparation under simple conditions of a broad range of S-aryl phosphorothioates, including complex molecules (e.g., dinucleotide or TADDOL derivatives), as well as other related organophosphorus compounds arylated at a chalcogen. The reaction proceeds with a full retention of the stereogenic center at the phosphorus atom, opening convenient access to P-chiral products. The mechanism of the reaction was established using DFT calculations.
Project description:The chemoselective reaction of the C- followed by the O-centered naphthyl radicals with the more electron-deficient hypervalent bond of the diaryliodonium(III) salts is described. This discovered reactivity constitutes a new activation mode of the diaryliodonium(III) salts which enabled a one-pot doubly arylation of naphthols through the sequential C s p 2 - C s p 2 /O- C s p 2 bond formation. The naphthyl radicals were generated in the reaction by the tetramethylpiperidinyl radical (TMP·) which resulted from the homolytic fragmentation of the precursor TMP2O. Experimental and DFT calculations provided a complete panorama of the reaction mechanism.
Project description:A successful DNA-encoded library (DEL) will consist of diverse skeletons and cover chemical space as comprehensive as possible to fully realize its potential in drug discovery and chemical biology. However, the lack of versatile on-DNA arylation methods for phenols that are less nucleophilic and reactive poses a great hurdle for DEL to include diaryl ether, a privileged chemotype in pharmaceuticals and natural products. This work describes the use of "substrate activation" approach to address the arylation of DNA-conjugated phenols. Diaryliodonium salt, a highly electrophilic and reactive arylation reagent, is employed as Ar+ sources to ensure highly selective on-DNA arylation of phenols and oximes with both high yields and DNA fidelity. Notably, the new on-DNA arylation reaction can be applied to the late-stage modification of peptides containing tyrosine side-chain and to synthesize DNA-tagged analogues of existing drug molecules such as sorafenib, a known pan-kinase inhibitor. The new on-DNA diaryliodonium salts chemistry affords a greater flexibility in DEL design and synthesis.