301665-60-1Relevant articles and documents
Electroreductive Carbofunctionalization of Alkenes with Alkyl Bromides via a Radical-Polar Crossover Mechanism
Zhang, Wen,Lin, Song
supporting information, p. 20661 - 20670 (2020/12/23)
Electrochemistry grants direct access to reactive intermediates (radicals and ions) in a controlled fashion toward selective organic transformations. This feature has been demonstrated in a variety of alkene functionalization reactions, most of which proceed via an anodic oxidation pathway. In this report, we further expand the scope of electrochemistry to the reductive functionalization of alkenes. In particular, the strategic choice of reagents and reaction conditions enabled a radical-polar crossover pathway wherein two distinct electrophiles can be added across an alkene in a highly chemo- and regioselective fashion. Specifically, we used this strategy in the intermolecular carboformylation, anti-Markovnikov hydroalkylation, and carbocarboxylation of alkenes - reactions with rare precedents in the literature - by means of the electroreductive generation of alkyl radical and carbanion intermediates. These reactions employ readily available starting materials (alkyl halides, alkenes, etc.) and simple, transition-metal-free conditions and display broad substrate scope and good tolerance of functional groups. A uniform protocol can be used to achieve all three transformations by simply altering the reaction medium. This development provides a new avenue for constructing Csp3-Csp3 bonds.
Cyclometalated Ruthenium Catalyst Enables Ortho-Selective C–H Alkylation with Secondary Alkyl Bromides
Wang, Gang-Wei,Wheatley, Matthew,Simonetti, Marco,Cannas, Diego M.,Larrosa, Igor
supporting information, p. 1459 - 1468 (2020/05/25)
Although Ru-catalyzed meta-selective sp2 C–H alkylation with secondary alkyl halides is well established, ortho selectivity has never been achieved. We demonstrate that the use of a cyclometalated Ru-complex, RuBnN, as the catalyst results in a complete switch of the inherent meta-selectivity to ortho selectivity in the Ru-catalyzed sp2 C–H alkylation reaction with unactivated secondary alkyl halides. The high catalytic activity of RuBnN allows mild reaction conditions that result in a transformation of broad scope and versatility. Preliminary mechanistic studies suggest that a bis-cycloruthenated species is the key intermediate undergoing oxidative addition with the alkyl bromides, thus avoiding the more common SET pathway associated with meta-selectivity. Direct C–H functionalization is a powerful tool for milder and more environmentally friendly syntheses of biologically active compounds, as well as offering easy access to unexplored chemical space in drug discovery. However, major challenges remain for these methods to be widely applicable. The development of new catalysts with diverse and superior reactivity is key to address these challenges. Here, we show for the first time that cyclometalated Ru-complexes are able to catalyze the directed ortho-C–H alkylation of arenes with secondary alkyl bromides, enabling the late-stage functionalization and diversification of pharmaceuticals. The obtained regioselectivity is in stark contrast to that delivered by the commonly used arene-bound Ru-complexes, which afford exclusive meta-alkylation. Our work points a way to further rationally design next-generation Ru-catalysts with improved control over selectivity and reactivity, and a richer synthetic toolbox for chemists in the future. Here, we report the first ortho-selective sp2 C–H bond alkylation with secondary alkyl bromides in the Ru catalytic platform, enabled by cyclometalated ruthenium(II) complex RuBnN. Mechanistic studies indicate that the formation of a bis-cycloruthenated intermediate enables an oxidative addition to occur, thus avoiding the single-electron transfer (SET) pathway associated with meta-selectivity in other Ru catalytic systems. The reaction is tolerant of a variety of medicinally relevant functional groups and has been used to modify existing pharmaceuticals.
Narciclasine derivative, and preparation and application thereof in preparation of antitumor drugs
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Paragraph 0169; 0170; 0171, (2017/04/28)
The invention provides a narciclasine derivative represented by the following structural formula I, wherein R1 is alkyl, cycloalkyl, benzyl or substituted benzyl, R2 is alkyl, cycloalkyl, benzyl or substituted benzyl, and n is an integer from 1 to 10. The narciclasine derivative is subjected to a tumor cell toxicity killing effect test, and results prove that the narciclasine derivative has strong toxicity killing effects on lung gland tumor cells, intestinal tumor cells, breast tumor cells, liver tumor cells, prostate tumor cells, melanoma tumor cells, endometrial tumor cells and neuroglia tumor cells, so the narciclasine derivative can be used for preparation of antitumor drugs. The invention provides a preparation method of the narciclasine derivative. The narciclasine derivative has a novel side-chain structure, shows excellent inhibitory activity on a variety of tumor cell strains, has drug efficacy better than that of narciclasine, allows toxic and side effects of the compound to be improved, provides new drugs for treatment of malignant tumors, and is of great clinical application value.
A cascade Aza-Cope/Aza-prins cyclization leading to piperidine derivatives
Nallasivam, Jothi L.,Fernandes, Rodney A.
, p. 2012 - 2022 (2015/03/18)
The cascade aza-Cope/aza-Prins cyclization of homoallylamines to give substituted piperidines has been explored. The use of glyoxalic acid as the carbonyl component afforded bicyclic structures as a result of the internal carboxylate anion trapping the intermediate cation. The unimolecular bis-, tris-, and tetrakis(homoallylamine)s efficiently delivered the appended bis-, tris- and tetrakis(piperidine-4-ol)s (tripod and crucifix shape, respectively) as new entities. The latter compound served as an excellent ligand in the Suzuki-Miyaura cross-coupling reaction to synthesize incrustoporin. The cascade aza-Cope/aza-Prins cyclization of homoallylamines to give substituted piperidines is described. A unimolecular tetrapiperidine derivative, which resulted from this strategy, was employed as a ligand in the Suzuki-Miyaura cross-coupling reaction of an α-iodobutenolide with an arylboronic acid in an efficient synthesis of incrustoporin and its analogues.
