143097-80-7Relevant academic research and scientific papers
Catalytic Access to Alkyl Bromides, Chlorides and Iodides via Visible Light-Promoted Decarboxylative Halogenation
Candish, Lisa,Standley, Eric A.,Gómez-Suárez, Adrián,Mukherjee, Satobhisha,Glorius, Frank
, p. 9971 - 9974 (2016)
Herein is reported the catalytic, visible light-promoted, decarboxylative halogenation (bromination, chlorination, and iodination) of aliphatic carboxylic acids. This operationally-simple reaction tolerates a range of functional groups, proceeds at room temperature, and is redox neutral. By employing an iridium photocatalyst in concert with a halogen atom source, the use of stoichiometric metals such as silver, mercury, thallium, and lead can be circumvented. This reaction grants access to valuable synthetic building blocks from the large pool of cheap, readily available carboxylic acids.
Regioselective Hydroalkylation of Vinylarenes by Cooperative Cu and Ni Catalysis
Ravn, Anne K.,Johansen, Martin B.,Skrydstrup, Troels
supporting information, (2021/12/14)
Disclosed here is a dual copper and nickel catalytic system with a silyl hydride source for promoting the linear selective hydroalkylation of vinylarenes. This carbon–carbon bond-forming protocol is applied to couple a variety of functionalized vinylarenes with alkyl halides applying a nickel(II) NNN pincer complex in the presence of an NHC-ligated copper catalyst. This combination allows for a 1 mol % loading of the nickel catalyst leading to turnover numbers of up to 72. Over 40 examples are presented, including applications for pharmaceutical diversification. Labeling experiments demonstrated the regioselectivity of the reaction and revealed that the copper catalyst plays a crucial role in enhancing the rate for formation of the reactive linear alkyl nickel complex. Overall, the presented work provides a complimentary approach for hydroalkylation reactions, whilst providing a preliminary mechanistic understanding of the cooperativity between the copper and nickel complexes.
Air-Stable PdI Dimer Enabled Remote Functionalization: Access to Fluorinated 1,1-Diaryl Alkanes with Unprecedented Speed
Kundu, Gourab,Opincal, Filip,Schoenebeck, Franziska,Sperger, Theresa
supporting information, (2021/11/30)
While remote functionalization via chain walking has the potential to enable access to molecules via novel disconnections, such processes require relatively long reaction times and can be in need of elevated temperatures. This work features a remote arylation in less than 10 min reaction time at room temperature over a distance of up to 11 carbons. The unprecedented speed is enabled by the air-stable PdI dimer [Pd(μ-I)(PCy2tBu)]2, which in contrast to its PtBu3 counterpart does not trigger direct coupling at the initiation site, but regioconvergent and chemoselective remote functionalization to yield valuable fluorinated 1,1-diaryl alkanes. Our combined experimental and computational studies rationalize the origins of switchability, which are primarily due to differences in dispersion interactions.
Regiodivergent Conversion of Alkenes to Branched or Linear Alkylpyridines
Kim, Minseok,Shin, Sanghoon,Koo, Yejin,Jung, Sungwoo,Hong, Sungwoo
supporting information, p. 708 - 713 (2022/01/20)
Herein we report a practical protocol for the visible-light-induced regiodivergent radical hydropyridylation of unactivated alkenes using pyridinium salts. This approach provides a unified synthetic platform to control the regioselectivity of the synthesis of linear or branched C4-alkylated pyridines. A remarkable selectivity switch from the anti-Markovnikov to the Markovnikov product can be achieved by the addition of tetrabutylammonium bromide. The versatility of this protocol is further demonstrated based on the late-stage functionalization in pharmaceuticals.
One-Pot Deoxygenation and Substitution of Alcohols Mediated by Sulfuryl Fluoride
Epifanov, Maxim,Mo, Jia Yi,Dubois, Rudy,Yu, Hao,Sammis, Glenn M.
supporting information, p. 3768 - 3777 (2021/03/01)
Sulfuryl fluoride is a valuable reagent for the one-pot activation and derivatization of aliphatic alcohols, but the highly reactive alkyl fluorosulfate intermediates limit both the types of reactions that can be accessed as well as the scope. Herein, we report the SO2F2-mediated alcohol substitution and deoxygenation method that relies on the conversion of fluorosulfates to alkyl halide intermediates. This strategy allows the expansion of SO2F2-mediated one-pot processes to include radical reactions, where the alkyl halides can also be exploited in the one-pot deoxygenation of primary alcohols under mild conditions (52-95% yield). This strategy can also enhance the scope of substitutions to nucleophiles that are previously incompatible with one-pot SO2F2-mediated alcohol activation and enables substitution of primary and secondary alcohols in 54-95% yield. Chiral secondary alcohols undergo a highly stereospecific (90-98% ee) double nucleophilic displacement with an overall retention of configuration.
Ni-Catalyzed Formal Cross-Electrophile Coupling of Alcohols with Aryl Halides
Lin, Quan,Ma, Guobin,Gong, Hegui
, p. 14102 - 14109 (2021/11/20)
Direct coupling of unactivated alcohols remains a challenge in current synthetic chemistry. We herein demonstrate a strategy building upon in situ halogenation/reductive coupling of alcohols with aryl halides to forge Csp2-Csp3 bonds. The combination of 2-chloro-3-ethylbenzo[d]oxazol-3-ium salt (CEBO) and TBAB as the mild bromination reagents enables rapid transformation of a wide range of alcohols to their bromide counterparts within one to 5 min in CH3CN and DMF, which is compatible with the Ni-catalyzed cross-electrophile coupling conditions in the presence of a chemical reductant. The present method is suitable for arylation of a myriad of structurally complex alcohols with no need for prepreparation of alkyl halides. More importantly, the mild and kinetically rapid bromination process has shown good selectivity in the bromination/arylation of symmetric diols and less sterically hindered hydroxyl groups in polyols, thus offering promise for selective functionalization of diols and polyols without laborious protecting/deprotecting operations. The practicality of this work is also evident in the arylation of a number of carbohydrates, drug compounds, and naturally occurring alcohols.
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.
Visible Light-Mediated Conversion of Alcohols to Bromides by a Benzothiadiazole-Containing Organic Photocatalyst
Li, Run,Gehrig, Dominik W.,Ramanan, Charusheela,Blom, Paul W. M.,Kohl, Fabien F.,Wagner, Manfred,Landfester, Katharina,Zhang, Kai A. I.
, p. 3852 - 3859 (2019/07/15)
The search for metal-free, stable and high effective photocatalysts with sufficient photo-redox potentials remains a key challenge for organic chemists. Here, we present a benzothiadiazole-containing molecular organic photocatalyst with redox potentials of ?1.30 V and +1.64 V vs. SCE. The singlet state lifetime is 13 ns. Direct conversion from aliphatic alcohols to bromides has been conducted with the designed organic photocatalyst under visible light irradiation with high efficiency and selectivity. The catalytic efficiency of the novel benzothiadiazole-based photocatalyst is comparable with the state-of-art metal and non-metal catalysts. Furthermore, advanced photophysical studies including time-resolved photoluminescence and transient absorption spectroscopy offer a powerful support for photo-induced electron transfer from photocatalyst to the reactive substrates. Lastly, no photo-bleaching effect is observed, demonstrating the high stability and recyclable of the designed organic photocatalyst. (Figure presented.).
Nickel-catalyzed alkyl-alkyl cross-coupling reactions of non-activated secondary alkyl bromides with aldehydes as alkyl carbanion equivalents
Zhu, Chenghao,Zhang, Junliang
supporting information, p. 2793 - 2796 (2019/03/06)
A novel nickel-catalyzed alkyl-alkyl cross coupling of non-activated secondary alkyl bromides with aldehydes via hydrazone intermediates has been developed. Aldehydes as alkyl carbanion equivalents replace traditional organometallic reagents. This coupling occurs on the carbon of the hydrazone rather than the nitrogen. In addition, non-activated primary and tertiary alkyl bromides also undergo the cross-coupling reaction to form new C(sp3)-C(sp3) bonds in moderate yields.
Synthesis of Alkyl Halides from Aldehydes via Deformylative Halogenation
Liang, Shengzong,Kumon, Tatsuya,Angnes, Ricardo A.,Sanchez, Melissa,Xu, Bo,Hammond, Gerald B.
, p. 3848 - 3854 (2019/05/24)
An unprecedented deformylative halogenation of aldehydes to alkyl halides is presented. Under oxidative conditions, 1,4-dihydropyridine (DHP), derived from an aldehyde, generated a C(sp3)- radical that coupled with a halogen radical that was generated from inexpensive and atom-economical halogen sources (NaBr, NaI, or HCl), to yield an alkyl halide. Because of the mild conditions, a wide range of functional groups were tolerated, and excellent site selectivity was achieved.
