共查询到20条相似文献,搜索用时 0 毫秒
1.
Wei Wang Dr. Mélanie M. Lorion Oscar Martinazzoli Prof. Dr. Lutz Ackermann 《Angewandte Chemie (International ed. in English)》2018,57(33):10554-10558
Late‐stage BODIPY diversification of structurally complex amino acids and peptides was accomplished by racemization‐free palladium‐catalyzed C(sp3)?H activation. Transformative fluorescence modification proved viable by triazole‐assisted C(sp3)?H arylation in a chemo‐ and site‐selective fashion, providing modular access to novel BODIPY peptide sensors. 相似文献
2.
《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2017,129(1):320-324
Despite the importance of stapled peptides for drug discovery, only few practical processes to prepare cross‐linked peptides have been described; thus the structural diversity of available staple motifs is currently limited. At the same time, C−H activation has emerged as an efficient approach to functionalize complex molecules. Although there are many reports on the C−H functionalization of amino acids, examples of post‐synthetic peptide C−H modification are rare and comprise almost only C(sp2)−H activation. Herein, we report the development of a palladium‐catalyzed late‐stage C(sp3)−H activation method for peptide stapling, affording an unprecedented hydrocarbon cross‐link. This method was first employed to prepare a library of stapled peptides in solution. The compatibility with various amino acids as well as the influence of the size (i ,i +3 and i ,i +4) and length of the staple were investigated. Finally, a simple solid‐phase procedure was also established. 相似文献
3.
Steric Effect of Carboxylate Ligands on Pd‐Catalyzed Intramolecular C(sp2)–H and C(sp3)–H Arylation Reactions 下载免费PDF全文
Yutaka Tanji Naoya Mitsutake Prof. Dr. Tetsuaki Fujihara Prof. Dr. Yasushi Tsuji 《Angewandte Chemie (International ed. in English)》2018,57(32):10314-10317
A bulky carboxylic acid bearing three cyclohexylmethyl substituents at the α‐position, namely, tri(cyclohexylmethyl)acetic acid, is demonstrated to act as an efficient ligand source in Pd‐catalyzed intramolecular C(sp2)?H and C(sp3)?H arylation reactions. The reactions proceed smoothly under mild reaction conditions, even at room temperature due to the steric bulk of the carboxylate ligands, which accelerates the rate‐determining C?H bond activation step in the catalytic cycle. 相似文献
4.
Han Seul Park Zhoulong Fan Ru‐Yi Zhu Jin‐Quan Yu 《Angewandte Chemie (International ed. in English)》2020,59(31):12853-12859
Reported herein is the distal γ‐C(sp3)?H olefination of ketone derivatives and free carboxylic acids. Fine tuning of a previously reported imino‐acid directing group and using the ligand combination of a mono‐N‐protected amino acid (MPAA) and an electron‐deficient 2‐pyridone were critical for the γ‐C(sp3)?H olefination of ketone substrates. In addition, MPAAs enabled the γ‐C(sp3)?H olefination of free carboxylic acids to form diverse six‐membered lactones. Besides alkyl carboxylic acids, benzylic C(sp3)?H bonds also could be functionalized to form 3,4‐dihydroisocoumarin structures in a single step from 2‐methyl benzoic acid derivatives. The utility of these protocols was demonstrated in large scale reactions and diversification of the γ‐C(sp3)?H olefinated products. 相似文献
5.
Mlanie M. Lorion Nikolaos Kaplaneris Jongwoo Son Rositha Kuniyil Lutz Ackermann 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(6):1698-1702
Bioorthogonal late‐stage diversification of structurally complex peptides has enormous potential for drug discovery and molecular imaging. In recent years, transition‐metal‐catalyzed C?H activation has emerged as an increasingly viable tool for peptide modification. Despite major accomplishments, these strategies largely rely on expensive palladium catalysts. We herein report an unprecedented cobalt(III)‐catalyzed peptide C?H activation, which enables the direct C?H functionalization of structurally complex peptides, and sets the stage for a multicatalytic C?H activation/alkene metathesis/hydrogenation strategy for the assembly of novel cyclic peptides. 相似文献
6.
Nikolaos Kaplaneris Torben Rogge Rongxin Yin Hui Wang Giedre Sirvinskaite Lutz Ackermann 《Angewandte Chemie (International ed. in English)》2019,58(11):3476-3480
Bioorthogonal C?H allylation with ample scope was accomplished through a versatile manganese(I)‐catalyzed C?H activation for the late‐stage diversification of structurally complex peptides. The unique robustness of the manganese(I) catalysis manifold was reflected by full tolerance of sensitive functional groups, such as iodides, esters, amides, and OH‐free hydroxy groups, thereby setting the stage for the racemization‐free synthesis of C?H fused peptide hybrids featuring steroids, drug molecules, natural products, nucleobases, and saccharides. 相似文献
7.
Dr. Shengqing Ye Dr. Weibo Yang Timothy Coon Dewey Fanning Tim Neubert Dean Stamos Prof. Dr. Jin‐Quan Yu 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(14):4748-4752
PdII‐catalyzed C(sp3)?H arylation of saturated heterocycles with a wide range of aryl iodides is enabled by an N‐heterocyclic carbene (NHC) ligand. A C(sp3)?H insertion step by the PdII/NHC complex in the absence of ArI is demonstrated experimentally for the first time. Experimental data suggests that the previously established NHC‐mediated Pd0/PdII catalytic manifold does not operate in this reaction. This transformation provides a new approach for diversifying pharmaceutically relevant piperidine and tetrahydropyran ring systems. 相似文献
8.
Palladium‐Catalyzed γ‐C(sp3)−H Arylation of Thiols by a Detachable Protecting/Directing Group 下载免费PDF全文
Likun Jin Jianchun Wang Prof. Dr. Guangbin Dong 《Angewandte Chemie (International ed. in English)》2018,57(38):12352-12355
Reported herein is a palladium‐catalyzed, directed γ‐C(sp3)?H arylation of protected thiols. The key is to utilize Michael acceptors as a dual reagent to install a protecting/directing group on thiols by a thiol‐Michael click reaction, and remove it later under basic conditions. The C?H arylation proceeds with high functional‐group tolerance and the deprotected thiols can be further transformed into other sulfur‐containing compounds. This unique mode of activation could open the door for site‐selective functionalization of thiols or other sulfur‐containing compounds at unactivated positions. 相似文献
9.
Zengbing Bai Chuangxu Cai Wangjian Sheng Yuxiang Ren Huan Wang 《Angewandte Chemie (International ed. in English)》2020,59(34):14686-14692
Transition‐metal‐catalyzed C?H activation has shown potential in the functionalization of peptides with expanded structural diversity. Herein, the development of late‐stage peptide macrocyclization methods by palladium‐catalyzed site‐selective C(sp2)?H olefination of tryptophan residues at the C2 and C4 positions is reported. This strategy utilizes the peptide backbone as endogenous directing groups and provides access to peptide macrocycles with unique Trp–alkene crosslinks. 相似文献
10.
Site‐Selective δ‐C(sp3)−H Alkylation of Amino Acids and Peptides with Maleimides via a Six‐Membered Palladacycle 下载免费PDF全文
Bei‐Bei Zhan Ya Li Jing‐Wen Xu Xing‐Liang Nie Dr. Jun Fan Liang Jin Prof. Dr. Bing‐Feng Shi 《Angewandte Chemie (International ed. in English)》2018,57(20):5858-5862
The site‐selective functionalization of unactivated C(sp3)?H bonds remains one of the greatest challenges in organic synthesis. Herein, we report on the site‐selective δ‐C(sp3)?H alkylation of amino acids and peptides with maleimides via a kinetically less favored six‐membered palladacycle in the presence of more accessible γ‐C(sp3)?H bonds. Experimental studies revealed that C?H bond cleavage occurs reversibly and preferentially at γ‐methyl over δ‐methyl C?H bonds while the subsequent alkylation proceeds exclusively at the six‐membered palladacycle that is generated by δ‐C?H activation. The selectivity can be explained by the Curtin–Hammett principle. The exceptional compatibility of this alkylation with various oligopeptides renders this procedure valuable for late‐stage peptide modifications. Notably, this process is also the first palladium(II)‐catalyzed Michael‐type alkylation reaction that proceeds through C(sp3)?H activation. 相似文献
11.
Chao Wang Rupeng Qi Hongxiang Xue Yuxuan Shen Min Chang Yaqiong Chen Rui Wang Zhaoqing Xu 《Angewandte Chemie (International ed. in English)》2020,59(19):7461-7466
Disclosed herein is the visible‐light‐promoted deaminative C(sp3)?H alkylation of glycine and peptides using Katritzky salts as electrophiles. Simple reaction conditions and excellent functional‐group tolerance provide a general strategy for the efficient preparation of unnatural α‐amino acids and precise modification of peptides with unnatural α‐amino‐acid residues. Mechanistic studies suggest that visible‐light‐promoted intermolecular charge transfer within a glycine–Katritzky salt electron donor‐acceptor (EDA) complex induces a single‐electron transfer process without the assistance of photocatalyst. 相似文献
12.
Dr. Suhua Li Ru‐Yi Zhu Dr. Kai‐Jiong Xiao Prof. Dr. Jin‐Quan Yu 《Angewandte Chemie (International ed. in English)》2016,55(13):4317-4321
PdII‐catalyzed arylation of γ‐C(sp3)?H bonds of aliphatic acid‐derived amides was developed by using quinoline‐based ligands. Various γ‐aryl‐α‐amino acids were prepared from natural amino acids using this method. The influence of ligand structure on reactivity was also systematically investigated. 相似文献
13.
Kiron Kumar Ghosh Alexander Uttry Arup Mondal Francesca Ghiringhelli Philipp Wedi Manuel van Gemmeren 《Angewandte Chemie (International ed. in English)》2020,59(31):12848-12852
We report the ligand‐enabled C?H activation/olefination of free carboxylic acids in the γ‐position. Through an intramolecular Michael addition, δ‐lactones are obtained as products. Two distinct ligand classes are identified that enable the challenging palladium‐catalyzed activation of free carboxylic acids in the γ‐position. The developed protocol features a wide range of acid substrates and olefin reaction partners and is shown to be applicable on a preparatively useful scale. Insights into the underlying reaction mechanism obtained through kinetic studies are reported. 相似文献
14.
Catalytic C(sp3)−H Arylation of Free Primary Amines with an exo Directing Group Generated In Situ 下载免费PDF全文
Chengpeng Wang David M. Magness Prof. Guangbin Dong 《Angewandte Chemie (International ed. in English)》2016,55(31):9084-9087
Herein, we report the palladium‐catalyzed direct arylation of unactivated aliphatic C?H bonds in free primary amines. This method takes advantage of an exo‐imine‐type directing group (DG) that can be generated and removed in situ. A range of unprotected aliphatic amines are suitable substrates, undergoing site‐selective arylation at the γ‐position. Methyl as well as cyclic and acyclic methylene groups can be activated. Furthermore, when aniline‐derived substrates were used, preliminary success with δ‐C?H arylation was achieved. The feasibility of using the DG component in a catalytic fashion was also demonstrated. 相似文献
15.
16.
Abolghasem Bakhoda Quan Jiang Yosra M. Badiei Jeffery A. Bertke Thomas R. Cundari Timothy H. Warren 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(11):3459-3463
Undirected C(sp3)?H functionalization reactions often follow site‐selectivity patterns that mirror the corresponding C?H bond dissociation energies (BDEs). This often results in the functionalization of weaker tertiary C?H bonds in the presence of stronger secondary and primary bonds. An important, contemporary challenge is the development of catalyst systems capable of selectively functionalizing stronger primary and secondary C?H bonds over tertiary and benzylic C?H sites. Herein, we report a Cu catalyst that exhibits a high degree of primary and secondary over tertiary C?H bond selectivity in the amidation of linear and cyclic hydrocarbons with aroyl azides ArC(O)N3. Mechanistic and DFT studies indicate that C?H amidation involves H‐atom abstraction from R‐H substrates by nitrene intermediates [Cu](κ2‐N,O‐NC(O)Ar) to provide carbon‐based radicals R. and copper(II)amide intermediates [CuII]‐NHC(O)Ar that subsequently capture radicals R. to form products R‐NHC(O)Ar. These studies reveal important catalyst features required to achieve primary and secondary C?H amidation selectivity in the absence of directing groups. 相似文献
17.
Continuous‐Flow Synthesis and Derivatization of Aziridines through Palladium‐Catalyzed C(sp3)−H Activation 下载免费PDF全文
Jacek Zakrzewski Adam P. Smalley Dr. Mikhail A. Kabeshov Prof. Matthew J. Gaunt Prof. Alexei A. Lapkin 《Angewandte Chemie (International ed. in English)》2016,55(31):8878-8883
A continuous‐flow synthesis of aziridines by palladium‐catalyzed C(sp3)?H activation is described. The new flow reaction could be combined with an aziridine‐ring‐opening reaction to give highly functionalized aliphatic amines through a consecutive process. A predictive mechanistic model was developed and used to design the C?H activation flow process and illustrates an approach towards first‐principles design based on novel catalytic reactions. 相似文献
18.
Palladium(0)/PAr3‐Catalyzed Intermolecular Amination of C(sp3)H Bonds: Synthesis of β‐Amino Acids 下载免费PDF全文
Jian He Toshihiko Shigenari Prof. Dr. Jin‐Quan Yu 《Angewandte Chemie (International ed. in English)》2015,54(22):6545-6549
An intermolecular C(sp3)? H amination using a Pd0/PAr3 catalyst was developed. The reaction begins with oxidative addition of R2N? OBz to a Pd0/PAr3 catalyst and subsequent cleavage of a C(sp3)? H bond by the generated Pd? NR2 intermediate. The catalytic cycle proceeds without the need for external oxidants in a similar manner to the extensively studied palladium(0)‐catalyzed C? H arylation reactions. The electron‐deficient triarylphosphine ligand is crucial for this C(sp3)? H amination reaction to occur. 相似文献