3219-55-4Relevant academic research and scientific papers
Rhodium(III)-Catalyzed Aerobic Oxidative C-H Olefination of Unsaturated Acrylamides with Unactivated Olefins
Logeswaran, Ravichandran,Jeganmohan, Masilamani
supporting information, p. 767 - 771 (2021/02/06)
A rhodium(III)-catalyzed aerobic oxidative cross-coupling of acrylamides with unactivated alkenes via vinylic C-H activation has been developed. The present cross-coupling reaction was examined with a variety of differently functionalized acrylamides and unactivated olefins. In these reactions, highly valuable amide-functionalized butadienes were prepared in good to excellent yields. This protocol was also compatible with Weinreb amides. A possible reaction mechanism involving the chelation-assisted vinylic C-H activation via a carboxylate-assisted deprotonation pathway is proposed.
Effect of Transition Metals on Chemodivergent Cross-Coupling of Acrylamides with Vinyl Acetate via C-H Activation
Logeswaran, Ravichandran,Jeganmohan, Masilamani
supporting information, p. 5679 - 5683 (2021/08/03)
A novel chemodivergent cross-coupling of acrylamides and vinyl acetates has been realized via metal-catalyzed vinylic C-H activation. The selective olefinic C-H vinylation and alkenylation reaction was examined with a variety of differently functionalized acrylamides. The reaction efficiently generates a range of highly synthetically valuable butadienes with good functional group tolerance in good to moderate yields. A possible catalytic reaction mechanism involving the chelation-assisted olefinic C-H activation via an acetate-assisted deprotonation pathway is proposed.
Synthesis of Benzoisoselenazolones via Rh(III)-Catalyzed Direct Annulative Selenation by Using Elemental Selenium
Xu-Xu, Qing-Feng,Nishii, Yuji,Uetake, Yuta,Sakurai, Hidehiro,Miura, Masahiro
supporting information, p. 17952 - 17959 (2021/11/16)
Isoselenazolone derivatives have attracted significant research interest because of their potent therapeutic activities and indispensable applications in organic synthesis. Efficient construction of functionalized isoselenazolone scaffolds is still challenging, and thus new synthetic approaches with improved operational simplicity have been of particular interest. In this manuscript, we introduce a rhodium-catalyzed direct selenium annulation by using stable and tractable elemental selenium. A series of benzamides as well as acrylamides were successfully coupled with selenium under mild reaction conditions, and the obtained isoselenazolones could be pivotal synthetic precursors for several organoselenium compounds. Based on the designed control experiments and X-ray absorption spectroscopy measurements, we propose an unprecedented selenation mechanism involving a highly electrophilic Se(IV) species as the reactive selenium donor. The reaction mechanism was further verified by a computational study.
Tunable Methacrylamides for Covalent Ligand Directed Release Chemistry
Reddi, Rambabu N.,Resnick, Efrat,Rogel, Adi,Rao, Boddu Venkateswara,Gabizon, Ronen,Goldenberg, Kim,Gurwicz, Neta,Zaidman, Daniel,Plotnikov, Alexander,Barr, Haim,Shulman, Ziv,London, Nir
supporting information, p. 4979 - 4992 (2021/05/04)
Targeted covalent inhibitors are an important class of drugs and chemical probes. However, relatively few electrophiles meet the criteria for successful covalent inhibitor design. Here we describe α-substituted methacrylamides as a new class of electrophiles suitable for targeted covalent inhibitors. While typically α-substitutions inactivate acrylamides, we show that hetero α-substituted methacrylamides have higher thiol reactivity and undergo a conjugated addition-elimination reaction ultimately releasing the substituent. Their reactivity toward thiols is tunable and correlates with the pKa/pKb of the leaving group. In the context of the BTK inhibitor ibrutinib, these electrophiles showed lower intrinsic thiol reactivity than the unsubstituted ibrutinib acrylamide. This translated to comparable potency in protein labeling, in vitro kinase assays, and functional cellular assays, with improved selectivity. The conjugate addition-elimination reaction upon covalent binding to their target cysteine allows functionalizing α-substituted methacrylamides as turn-on probes. To demonstrate this, we prepared covalent ligand directed release (CoLDR) turn-on fluorescent probes for BTK, EGFR, and K-RasG12C. We further demonstrate a BTK CoLDR chemiluminescent probe that enabled a high-throughput screen for BTK inhibitors. Altogether we show that α-substituted methacrylamides represent a new and versatile addition to the toolbox of targeted covalent inhibitor design.
Cobalt-Catalyzed Olefinic C-H Alkenylation/Alkylation Switched by Carbonyl Groups
Li, Tingyan,Shen, Cong,Sun, Yaling,Zhang, Jian,Xiang, Panjie,Lu, Xiunan,Zhong, Guofu
supporting information, p. 7772 - 7777 (2019/10/10)
The first cobalt-catalyzed cross-couplings between olefins has been demonstrated to provide C(alkenyl)-H alkenylation and alkylation products, using complex [Cp?Co(CO)I2]. While coupling partner acrylates afforded conjugated dienoates, α,β-unsaturated ketones led to γ-alkenyl ketones completely, representing a switchable C-H functionalization controlled by different carbonyl groups.
Mechanistic Insights into Temperature-Dependent Trithiocarbonate Chain-End Degradation during the RAFT Polymerization of N-Arylmethacrylamides
Abel, Brooks A.,McCormick, Charles L.
, p. 465 - 474 (2016/02/05)
Mechanistic insights into trithiocarbonate degradation during the RAFT polymerization of N-arylmethacrylamides are reported. Previous work by our group showed significant RAFT agent degradation during the polymerization of N-arylmethacryloyl sulfonamides at 70 °C. Herein we report the influence of methacrylamide structure on trithiocarbonate degradation during the RAFT polymerizations of N-phenylmethacrylamide (PhMA) and N-benzylmethacrylamide (BnMA) in DMF at 70 and 30 °C. UV-vis spectroscopy revealed trithiocarbonate degradation occurs exclusively after covalent addition of monomer to the RAFT agent, with 60% trithiocarbonate degradation occurring after 12 h during the polymerization of PhMA at 70 °C compared to only 3% degradation measured during the polymerization of BnMA under identical conditions. Small molecule analogues of trithiocarbonate-functional poly(PhMA) and poly(BnMA) were synthesized by single monomer unit insertion and the kinetics and byproducts of degradation investigated by in situ 1H NMR analysis at 70 °C. Trithiocarbonate degradation was ultimately shown to occur by N-phenyl-promoted, N-5 nucleophilic attack on the terminal thiocarbonyl by the ultimate methacrylamide unit.
High-valent palladium-promoted formal Wagner-Meerwein rearrangement
Wu, Hongmiao,Yang, Bin,Zhu, Lin,Lu, Ronghua,Li, Guigen,Lu, Hongjian
supporting information, p. 5804 - 5807 (2016/11/29)
An oxy-palladation, formal Wagner-Meerwein rearrangement and fluorination cascade has been established for generating fluorinated oxazolidine-2,4-diones and oxazolidin-2-ones. The reaction has a broad substrate scope in which both aryl and alkyl groups can be utilized as efficient migrating groups. Experimental evidence suggests that the reaction is initiated by anti-oxy-palladation of the olefin, followed by oxidative generation of an alkyl PdIV intermediate and a concerted migration-fluorination.
Thermodynamically controlled chemoselectivity in lipase-catalyzed aza-Michael additions
Rivera-Ramírez, José Domingo,Escalante, Jaime,López-Munguía, Agustín,Marty, Alain,Castillo, Edmundo
supporting information, p. 76 - 82 (2015/01/30)
Chemoselective synthesis of N-protected β-amino esters involving lipase-catalyzed aza-Michael additions and α,β-unsaturated precursors is mainly hampered by the two electrophilic sites present on these compounds. In order to control the chemoselectivity a solvent engineering strategy based on the thermodynamic behaviour of products in media of different polarity was designed. This strategy allowed to obtain aza-Michael adducts from benzylamine and different acrylates with high selectivity. In almost all reactions carried out in n-hexane, a non-polar solvent, aminolysis was avoided while the corresponding Michael adducts were exclusively synthesized in 53-78% yields. On the contrary, in reactions carried out in a polar solvent such as 2-methyl-2-butanol the aminolysis products were favoured. Thermodynamic analyses of these processes using the COSMO-RS method helped to understand some of the key factors affecting chemoselectivity and confirmed that a reliable estimation of the thermodynamic interactions of solutes and solvents allows an adequate selection of a reaction media that may lead to chemoselectivity.
Convenient synthesis of various substituted homotaurines from alk-2-enamides
Nai, Youfeng,Xu, Jiaxi
, p. 1355 - 1365 (2013/08/23)
Various substituted homotaurines (=3-aminopropane-1-sulfonic acids) 6 were readily synthesized in satisfactory to good yields via the Michael addition of thioacetic acid to alk-2-enamides 3 (→4), followed by LiAlH4 reduction (→5) and performic acid oxidation (Scheme 1). The configuration of 'anti'-disubstituted homotaurine 'anti'-6h was deduced from the 3-(acetylthio)alkanamide (=S-(3-amino-1,2-dimethyl-3-oxopropyl) ethanethioate)'anti'-4h formed in the Michael addition, which was identified via the Karplus equation analysis, and confirmed by X-ray diffraction analysis. The current route is an efficient method to synthesize diverse substituted homotaurines, including 1-, 2-, and N-monosubstituted, as well as 1,2-, 1,N-, 2,N-, and N,N-disubstituted homotaurines (Table). Copyright
Ir(III)-catalyzed mild C-H amidation of arenes and alkenes: An efficient usage of acyl azides as the nitrogen source
Ryu, Jaeyune,Kwak, Jaesung,Shin, Kwangmin,Lee, Donggun,Chang, Sukbok
supporting information, p. 12861 - 12868 (2013/09/23)
Reported herein is the development of the Ir(III)-catalyzed direct C-H amidation of arenes and alkenes using acyl azides as the nitrogen source. This procedure utilizes an in situ generated cationic half-sandwich iridium complex as a catalyst. The reaction takes place under very mild conditions, and a broad range of sp2 C-H bonds of chelate group-containing arenes and olefins are smoothly amidated with acyl azides without the intervention of the Curtius rearrangement. Significantly, a wide range of reactants of aryl-, aliphatic-, and olefinic acyl azides were all efficiently amidated with high functional group tolerance. Using the developed approach, Z-enamides were readily accessed with a complete control of regio- and stereoselectivity. The developed direct amidation proceeds in the absence of external oxidants and releases molecular nitrogen as a single byproduct, thus offering an environmentally benign process with wide potential applications in organic synthesis and medicinal chemistry.
