2110-18-1Relevant articles and documents
Ligand-controlled, Pd/CuH-catalyzed reductive cross-coupling of terminal alkenes and: N -heteroaryl bromides
Seo, Sanghyup,Kim, Donghyeon,Kim, Hyunwoo
supporting information, p. 11240 - 11243 (2021/11/09)
The reductive cross-coupling of terminal alkenes and N-heterocyclic bromides has been demonstrated by ligand optimization of Pd and CuH catalysis. The optimized ligands are Briphos, a π-acceptor monodentate phosphorus ligand, for Pd catalysis and DTB-DPPBz, a sterically bulky bidentate phosphorus ligand, for CuH catalysis. These conditions were further applied to the gram-scale production of clathryimine B. This journal is
Unlocking the Accessibility of Alkyl Radicals from Boronic Acids through Solvent-Assisted Organophotoredox Activation
Ranjan, Prabhat,Pillitteri, Serena,Coppola, Guglielmo,Oliva, Monica,Van der Eycken, Erik V.,Sharma, Upendra K.
, p. 10862 - 10870 (2021/09/08)
Despite their prevalence in organic synthesis, the application of boronic acids (BAs) as alkyl radical precursors in visible-light-assisted photocatalyzed reactions has been limited by their high oxidation potential. This study demonstrates the prominent
Ruthenium catalyzed β-selective alkylation of vinylpyridines with aldehydes/ketonesviaN2H4mediated deoxygenative couplings
Lv, Leiyang,Li, Chao-Jun
, p. 2870 - 2875 (2021/03/14)
Umpolung (polarity reversal) tactics of aldehydes/ketones have greatly broadened carbonyl chemistry by enabling transformations with electrophilic reagents and deoxygenative functionalizations. Herein, we report the first ruthenium-catalyzed β-selective alkylation of vinylpyridines with both naturally abundant aromatic and aliphatic aldehyde/ketonesviaN2H4mediated deoxygenative couplings. Compared with one-electron umpolung of carbonyls to alcohols, this two-electron umpolung strategy realized reductive deoxygenation targets, which were not only applicable to the regioselective alkylation of a broad range of 2/4-alkene substituted pyridines, but also amenable to challenging 3-vinyl and steric-embedded internal pyridines as well as their analogous heterocyclic structures.
ZnMe2-Mediated, Direct Alkylation of Electron-Deficient N-Heteroarenes with 1,1-Diborylalkanes: Scope and Mechanism
Jo, Woohyun,Baek, Seung-Yeol,Hwang, Chiwon,Heo, Joon,Baik, Mu-Hyun,Cho, Seung Hwan
supporting information, p. 13235 - 13245 (2020/09/01)
The regioselective, direct alkylation of electron-deficient N-heteroarenes is, in principle, a powerful and efficient way of accessing alkylated N-heteroarenes that are important core structures of many biologically active compounds and pharmaceutical agents. Herein, we report a ZnMe2-promoted, direct C2- or C4-selective primary and secondary alkylation of pyridines and quinolines using 1,1-diborylalkanes as alkylation sources. While substituted pyridines and quinolines exclusively afford C2-alkylated products, simple pyridine delivers C4-alkylated pyridine with excellent regioselectivity. The reaction scope is remarkably broad, and a range of C2- or C4-alkylated electron-deficient N-heteroarenes are obtained in good yields. Experimental and computational mechanistic studies imply that ZnMe2 serves not only as an activator of 1,1-diborylalkanes to generate (α-borylalkyl)methylalkoxy zincate, which acts as a Lewis acid to bind to the nitrogen atom of the heterocycles and controls the regioselectivity, but also as an oxidant for rearomatizing the dihydro-N-heteroarene intermediates to release the product.
Aryl-Nickel-Catalyzed Benzylic Dehydrogenation of Electron-Deficient Heteroarenes
Zhang, Pengpeng,Huang, David,Newhouse, Timothy R.
supporting information, p. 1757 - 1762 (2020/02/04)
This manuscript describes the first practical benzylic dehydrogenation of electron-deficient heteroarenes, including pyridines, pyrazines, pyrimidines, pyridazines, and triazines. This transformation allows for the efficient benzylic oxidation of heteroarenes to afford heterocyclic styrenes by the action of nickel catalysis paired with an unconventional bromothiophene oxidant.
Nickel-Catalyzed Cross-Electrophile Reductive Couplings of Neopentyl Bromides with Aryl Bromides
Biswas, Soumik,Qu, Bo,Desrosiers, Jean-Nicolas,Choi, Younggi,Haddad, Nizar,Yee, Nathan K.,Song, Jinghua J.,Senanayake, Chris H.
, p. 8214 - 8220 (2020/07/25)
5-Cyanoimidazole was identified as an inexpensive ligand for nickel-catalyzed cross-electrophile couplings by screening a diverse set of pharmaceutical compound library. A strategic screening approach led to the discovery of this novel ligand, which was successfully applied in the preparation of various alkylated arene products with good to high yields. Furthermore, the properties of this ligand allowed expanding the scope of reductive couplings to challenging substrates, such as sterically hindered neopentyl halides, which are known to generate motifs that are prevalent in biologically active molecules.
Potassium Amide-Catalyzed Benzylic C?H Bond Addition of Alkylpyridines to Styrenes
Zhai, Dan-Dan,Zhang, Xiang-Yu,Liu, Yu-Feng,Zheng, Lei,Guan, Bing-Tao
supporting information, p. 1650 - 1653 (2018/01/27)
The benzylic functionalization of alkylpyridines is an important pathway for pyridine derivatives synthesis. The reaction partners, however, were mostly limited to highly reactive polar electrophiles. Herein, we report a potassium amide-catalyzed selective benzylic C?H bond addition of alkylpyridines to styrenes. Potassium bis(trimethylsilyl)amide (KHMDS), a readily available Br?nsted base, showed excellent catalytic activity and chemoselectivity. A series of alkylpyridine derivatives, including benzylic quaternary carbon substituted pyridines, were obtained in good to high yield. Preliminary mechanistic studies revealed that the deprotonation equilibrium is probably responsible for the excellent selectivity.
Coupling of Challenging Heteroaryl Halides with Alkyl Halides via Nickel-Catalyzed Cross-Electrophile Coupling
Hansen, Eric C.,Li, Changfeng,Yang, Sihang,Pedro, Dylan,Weix, Daniel J.
, p. 7085 - 7092 (2017/07/26)
Despite their importance, the synthesis of alkylated heterocycles from the cross-coupling of Lewis basic nitrogen heteroaryl halides with alkyl halides remains a challenge. We report here a general solution to this challenge enabled by a new collection of ligands based around 2-pyridyl-N-cyanocarboxamidine and 2-pyridylcarboxamidine cores. Both primary and secondary alkyl halides can be coupled with 2-, 3-, and 4-pyridyl halides as well as other more complex heterocycles in generally good yields (41 examples, 69% ave yield).
Exhaustive Suzuki-Miyaura reactions of polyhalogenated heteroarenes with alkyl boronic pinacol esters
Laulhé, Sébastien,Blackburn, J. Miles,Roizen, Jennifer L.
supporting information, p. 7270 - 7273 (2017/07/11)
A novel Suzuki-Miyaura protocol is described that enables the exhaustive alkylation of polychlorinated pyridines. This method facilitates a formal synthesis of normuscopyridine and the rapid assembly of a dumbbell shaped portion of a [2]rotaxane.
Transition-Metal-Free Regioselective Alkylation of Pyridine N-Oxides Using 1,1-Diborylalkanes as Alkylating Reagents
Jo, Woohyun,Kim, Junghoon,Choi, Seoyoung,Cho, Seung Hwan
supporting information, p. 9690 - 9694 (2016/08/10)
Reported herein is an unprecedented base-promoted deborylative alkylation of pyridine N-oxides using 1,1-diborylalkanes as alkyl sources. The reaction proceeds efficiently for a wide range of pyridine N-oxides and 1,1-diborylalkanes with excellent regioselectivity. The utility of the developed method is demonstrated by the sequential C?H arylation and methylation of pyridine N-oxides. The reaction also can be applied for the direct introduction of a methyl group to 9-O-methylquinine N-oxide, thus it can serve as a powerful method for late-stage functionalization.
