61495-04-3Relevant academic research and scientific papers
Z-Selective Fluoroalkenylation of (Hetero)Aromatic Systems by Iodonium Reagents in Palladium-Catalyzed Directed C?H Activation
Tóth, Balázs L.,Sályi, Gerg?,Domján, Attila,Egyed, Orsolya,Bényei, Attila,Gonda, Zsombor,Novák, Zoltán
supporting information, p. 348 - 354 (2021/11/09)
The direct and catalytic incorporation of fluorine containing molecular motifs into organic compounds resulting high-value added chemicals represents a rapidly evolving part of synthetic methodologies, thus this area is in the focus of pharmaceutical and agrochemical research. Herein we report a stereoselective procedure for direct fluorovinylation of aromatic and heteroaromatic scaffolds. This methodology development has been realized by palladium-catalyzed ortho C?H activation reaction of aniline derivatives featuring the regioselectivity via directing groups such as secondary of tertiary amides, ureas or ketones. The application of non-symmetrical aryl(fluoroalkenyl)-iodonium salts as fluoroalkenylating agents allowed mild reaction conditions in general for this transformation. The scope and limitations have been thoroughly investigated and the feasibility has been demonstrated by more than 50 examples.
Equivalent Loading of Directed Arenes in Pd(II)-Catalyzed Oxidative Cross-Coupling of Aryl C-H Bonds at Room Temperature
Mei, Chong,Zhao, Mengdi,Lu, Wenjun
, p. 2714 - 2733 (2021/02/01)
The unsymmetrical biaryls (Ar1-Ar2) produced by the catalytic cross-couplings of aryl halides (Ar1-halo) with aryl metallics (Ar2-M) in the loading ratio of 1:1 are popular in chemical synthesis. In contrast, there has been less precedence on the same biaryls produced effectively from two normal aryl C-H bonds with equivalent loading. Here, we report that, in a palladium/oxidant/acid catalytic system at room temperature, one arene (Ar1-H, 1 equiv) can highly selectively couple with the other one (Ar2-H, 1 equiv) to afford the target Ar1-Ar2 just by controlling the directing groups and the substituted groups on their phenyl rings. The utility of this one-one cross-coupling is also demonstrated by synthesis of a few bioactive molecules.
Rhodium(III)-Catalyzed Synthesis of Skipped Enynes via C(sp3)–H Alkynylation of Terminal Alkenes
Della-Felice, Franco,Zanini, Margherita,Jie, Xiaoming,Tan, Eric,Echavarren, Antonio M.
supporting information, p. 5693 - 5698 (2021/02/09)
The RhIII-catalyzed allylic C?H alkynylation of non-activated terminal alkenes leads selectively to linear 1,4-enynes at room-temperature. The catalytic system tolerates a wide range of functional groups without competing functionalization at other positions. Similarly, the vinylic C?H alkynylation of α,β- and β,γ- unsaturated amides gives conjugated Z-1,3-enynes and E-enediynes.
Ligand Promoted Olefination of Anilides for Indirectly Introducing Fluorinated Functional Groups via Palladium Catalyst
Wang, Dongjie,Xu, Xu,Zhang, Jingyu,Zhao, Yingsheng
, p. 2696 - 2705 (2021/02/27)
We report a palladium-catalyzed, ligand promoted, C-H fluorine-containing olefination of anilides with 4-bromo-3,3,4,4-tetrafluorobutene as the fluorinated reagent, which has a potential transformation into other compounds due to its -CF2CF2Br functional group. -CF2CF2H was obtained by using the mild reducing agent sodium borohydride. Bioactive compounds such as aminoglutethimide derivative and propham were well-tolerated in this reaction, both of which highlight the synthetic importance of this method.
Highly Efficient and Practical Synthesis of the Key Intermediate of Telmisartan
Zhao, Jianhong,Xiong, Yicheng,Yang, Wu-Lin,Yang, Fan,Jin, Yu
, p. 1022 - 1027 (2021/04/12)
We reported herein an efficient and practical method to access 1,7′-dimethyl-2′-propyl-2,5′-bi(1H-benzimidazole) 1, a key intermediate for the synthesis of telmisartan. The synthetic route was based on readily available o-methylaniline as the starting material, and the target product 1 was prepared through a six-step process, including amidation, formylation, cyclization, hydrolysis, amidine, and oxidation. The overall yield for the preparation of 1 was 51.5% on the 100 g scale, with a purity of 99.91%. The salient features of this method include economic and easily available starting materials, operational simplicity, and environmentally friendly, which is suitable for the industrial production.
Late-Stage Diversification of Biarylphosphines through Rhodium(I)-Catalyzed C-H Bond Alkenylation with Internal Alkynes
Zhang, Zhuan,Cordier, Marie,Dixneuf, Pierre H.,Soulé, Jean-Fran?ois
supporting information, p. 5936 - 5940 (2020/07/30)
We report herein P(III)-directed C-H bond alkenylation of (dialkyl)- and (diaryl)biarylphosphines using internal alkynes. Chloride-free [Rh(OAc)(COD)]2 acts as a better catalyst than commercially available [RhCl(COD)]2. Conditions were developed to control the mono- and difunctionalization depending on the alkyne stoichiometry. One of these novel bisalkenylated (dialkyl)biarylphosphines was employed for the preparation of a palladium(II) complex, and some of these functionalized ligands outperformed their corresponding unfunctionalized phosphines in Pd-catalyzed amidation with sterically hindered aryl chlorides.
Para -Selective copper-catalyzed C(sp2)-H amidation/dimerization of anilides via a radical pathway
Viveki, Amol B.,Garad, Dnyaneshwar N.,Gonnade, Rajesh G.,Mhaske, Santosh B.
supporting information, p. 1565 - 1568 (2020/02/13)
Copper-catalyzed amidation/dimerization of anilides via regioselective C(sp2)-H functionalization is achieved. The para-selective amidation is accomplished on the anilide aromatic ring via a radical pathway leading to C-N bond formation in the presence of ammonium persulfate as a radical source/oxidant for the copper catalyst. The developed protocol tolerates a wide range of anilide substrates. The regioselectivity is confirmed by single-crystal X-ray studies.
Site-Selective C–H Functionalization of (Hetero)Arenes via Transient, Non-symmetric Iodanes
Fosu, Stacy C.,Hambira, Chido M.,Chen, Andrew D.,Fuchs, James R.,Nagib, David A.
supporting information, p. 417 - 428 (2019/02/14)
Fosu, Hambira, and colleagues describe the direct C–H functionalization of medicinally relevant arenes or heteroarenes. This strategy is enabled by transient generation of reactive, non-symmetric iodanes from anions and PhI(OAc)2. The site-selective incorporation of Cl, Br, OMs, OTs, and OTf to complex molecules, including within medicines and natural products, can be conducted by the operationally simple procedure included herein. A computational model for predicting site selectivity is also included. The discovery of new medicines is a time- and labor-intensive process that frequently requires over a decade to complete. A major bottleneck is the synthesis of drug candidates, wherein each complex molecule must be prepared individually via a multi-step synthesis, frequently requiring a week of effort per molecule for thousands of candidates. As an alternate strategy, direct, post-synthetic functionalization of a lead candidate could enable this diversification in a single operation. In this article, we describe a new method for direct manipulation of drug-like molecules by incorporation of motifs with either known pharmaceutical value (halides) or that permit subsequent conversion (pseudo-halides) to medicinally relevant analogs. This user-friendly strategy is enabled by combining commercial iodine reagents with salts and acids. We expect this simple method for selective, post-synthetic incorporation of molecular diversity will streamline the discovery of new medicines. A strategy for C–H functionalization of arenes and heteroarenes has been developed to allow site-selective incorporation of various anions, including Cl, Br, OMs, OTs, and OTf. This approach is enabled by in situ generation of reactive, non-symmetric iodanes by combining anions and bench-stable PhI(OAc)2. The utility of this mechanism is demonstrated via para-selective chlorination of medicinally relevant arenes, as well as site-selective C–H chlorination of heteroarenes. Spectroscopic, computational, and competition experiments describe the unique nature, reactivity, and selectivity of these transient, unsymmetrical iodanes.
Rhodium(III)-Catalyzed Directed C-H Dienylation of Anilides with Allenes Leads to Highly Conjugated Systems
Ghosh, Chiranjit,Nagtilak, Prajyot Jayadev,Kapur, Manmohan
supporting information, (2019/05/08)
Allenes are unique coupling partners in transition-metal-catalyzed C-H functionalization leading to a variety of products via alkenylation, allenylation, allylation, and annulation reactions. The outcome is governed by both the reactivity of the allene and the formation and stability of the organometallic intermediate. An efficient Rh(III)-catalyzed, weakly coordinating group-directed dienylation of electronically unbiased allenes is developed using an N-acyl amino acid as a ligand. Further elaboration of the dienylated products to construct polycyclic compounds is also described.
General rhodium-catalyzed oxidative cross-coupling reactions between anilines: Synthesis of unsymmetrical 2,2′-diaminobiaryls
Shi, Yang,Liu, Jiahui,Yang, Yudong,You, Jingsong
supporting information, p. 5475 - 5478 (2019/05/16)
Described herein is a dual chelation-assisted RhCl3-catalyzed oxidative C-H/C-H cross-coupling reaction of aniline derivatives. The highlight of this methodology is the chemo- and regioselective cross-coupling between electronically similar substrates, which represents a highly challenging task in oxidative Ar-H/Ar-H cross-coupling reactions. Furthermore, this Cp?-free catalytic reaction tolerates a range of functional groups and requires only a low molar ratio of coupling partners. These features expedite the synthesis of unsymmetrical 2,2′-diaminobiaryls.
