- Ligand-controlled, Pd/CuH-catalyzed reductive cross-coupling of terminal alkenes and: N -heteroaryl bromides
-
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
- Seo, Sanghyup,Kim, Donghyeon,Kim, Hyunwoo
-
supporting information
p. 11240 - 11243
(2021/11/09)
-
- Unlocking the Accessibility of Alkyl Radicals from Boronic Acids through Solvent-Assisted Organophotoredox Activation
-
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
- Ranjan, Prabhat,Pillitteri, Serena,Coppola, Guglielmo,Oliva, Monica,Van der Eycken, Erik V.,Sharma, Upendra K.
-
p. 10862 - 10870
(2021/09/08)
-
- Ruthenium catalyzed β-selective alkylation of vinylpyridines with aldehydes/ketonesviaN2H4mediated deoxygenative couplings
-
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.
- Lv, Leiyang,Li, Chao-Jun
-
p. 2870 - 2875
(2021/03/14)
-
- ZnMe2-Mediated, Direct Alkylation of Electron-Deficient N-Heteroarenes with 1,1-Diborylalkanes: Scope and Mechanism
-
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.
- Jo, Woohyun,Baek, Seung-Yeol,Hwang, Chiwon,Heo, Joon,Baik, Mu-Hyun,Cho, Seung Hwan
-
supporting information
p. 13235 - 13245
(2020/09/01)
-
- Aryl-Nickel-Catalyzed Benzylic Dehydrogenation of Electron-Deficient Heteroarenes
-
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.
- Zhang, Pengpeng,Huang, David,Newhouse, Timothy R.
-
supporting information
p. 1757 - 1762
(2020/02/04)
-
- Nickel-Catalyzed Cross-Electrophile Reductive Couplings of Neopentyl Bromides with Aryl Bromides
-
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.
- 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)
-
- Potassium Amide-Catalyzed Benzylic C?H Bond Addition of Alkylpyridines to Styrenes
-
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.
- Zhai, Dan-Dan,Zhang, Xiang-Yu,Liu, Yu-Feng,Zheng, Lei,Guan, Bing-Tao
-
supporting information
p. 1650 - 1653
(2018/01/27)
-
- Coupling of Challenging Heteroaryl Halides with Alkyl Halides via Nickel-Catalyzed Cross-Electrophile Coupling
-
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).
- Hansen, Eric C.,Li, Changfeng,Yang, Sihang,Pedro, Dylan,Weix, Daniel J.
-
p. 7085 - 7092
(2017/07/26)
-
- Exhaustive Suzuki-Miyaura reactions of polyhalogenated heteroarenes with alkyl boronic pinacol esters
-
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.
- Laulhé, Sébastien,Blackburn, J. Miles,Roizen, Jennifer L.
-
supporting information
p. 7270 - 7273
(2017/07/11)
-
- Transition-Metal-Free Regioselective Alkylation of Pyridine N-Oxides Using 1,1-Diborylalkanes as Alkylating Reagents
-
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.
- Jo, Woohyun,Kim, Junghoon,Choi, Seoyoung,Cho, Seung Hwan
-
supporting information
p. 9690 - 9694
(2016/08/10)
-
- Selective and Serial Suzuki-Miyaura Reactions of Polychlorinated Aromatics with Alkyl Pinacol Boronic Esters
-
Among cross-coupling reactions, the Suzuki-Miyaura transformation stands out because of its practical advantages, including the commercial availability and low toxicity of the required reagents, mild reaction conditions, and functional group compatibility. Nevertheless, few conditions can be used to cross-couple alkyl boronic acids or esters with aryl halides, especially 2-pyridyl halides. Herein, we describe two novel Suzuki-Miyaura protocols that enable selective conversion of polychlorinated aromatics, with a focus on reactions to convert 2,6-dichloropyridines to 2-chloro-6-alkylpyridines or 2-aryl-6-alkylpyridines.
- Laulhé, Sébastien,Blackburn, J. Miles,Roizen, Jennifer L.
-
supporting information
p. 4440 - 4443
(2016/09/09)
-
- Iron-catalyzed cross-coupling of aryltrimethylammonium triflates and alkyl Grignard reagents
-
Fe(acac)3 effectively catalyzes reaction of aryltrimethylammonium triflates with β-hydrogen-containing primary or secondary alkyl Grignard reagents in a mixed solvent of THF and NMP at room temperature. A series of functional groups are tolerated under the reaction conditions.
- Guo, Wang-Jun,Wang, Zhong-Xia
-
supporting information
p. 9580 - 9585
(2013/10/22)
-
- Zn-promoted regio- and sequence-selective one-pot joining reactions of three components: vinylpyridines, alkyl iodides, and carbonyl compounds (or nitriles)
-
Addition of alkyl iodides (3) into the solution containing 2-(or 4-)vinylpyridine (1 or 2) and carbonyl compounds (6) in the presence of Zn-powder (99.9%) in acetonitrile under refluxing brought about regio- and sequence-selective joining reaction of thre
- Mineyama, Kenji,Maekawa, Hirofumi,Kohsaka, Akihiro,Yamamoto, Yoshimasa,Nishiguchi, Ikuzo
-
experimental part
p. 7706 - 7711
(2009/12/04)
-
- HOMOLYTIC ADDITION OF ALKYLPYRIDINES TO PHENYLACETYLENE
-
The homolytic addition of 2-, 3-, and 4-methylpyridines and 2-methyl-5-ethylpyridine to phenylacetylene was studied under the conditions of peroxide initiation.The important role of polar factors in the reagents, affecting both the yields of 1-phenyl-3-pyridyl-1-alkenes and the ratio of cis and trans isomers, was demonstrated.
- Il'yasov, E. A.,Galust'yan, G. G.,Asadova, M. G.
-
p. 847 - 851
(2007/10/02)
-
- FREE-RADICAL PYRIDYLETHYLATION OF ARYLALKANES
-
2-(3-Arylpropyl)pyridines were synthesized in 30-54percent yields by the free-radical addition of toluene, o-, m-, and p-xylenes, and mesitylene to 2-vinylpyridine at 250-350 deg C.The products of rearrangement of the intermediate adduct radical with 1,3-H migration were isolated and identified.
- Galust'yan, G. G.,Il'yasov, E. A.,Kadyrov, Ch. Sh.
-
p. 307 - 310
(2007/10/02)
-
- 4-[[3-[α-Aminobenzyl]phenyl]methyl]morpholine and 4-[-[3-benzoylphenyl]ethyl]morpholine
-
N-{2, 3- and 4-[R1 -(phenyl)-C(=X)]-phenyl-lower-alkyl}amines, useful as anti-inflammatory agents, are prepared either by reduction of 2-, 3- or 4-[R1 -(phenyl)-CO]-phenyl-lower-alkanoylamines, which are also useful as anti-inflammatory agents; by benzoylating a phenyl-lower-alkylamine; by reaction of a 2-, 3- or 4-lithiophenyl-lower-alkylamine with a R1 -(phenyl)-carboxaldehyde, a R1 -(phenyl)-lower-alkyl ketone or a R1 -(phenyl)-carbonitrile; by reaction of a 2-, 3- or 4-[R1 -(phenyl)-CO]-phenyl-lower-alkyl tosylate with an appropriate amine; or by transformations involving manipulations of a carbonyl or carbinol group.
- -
-
-
- Intermediates for preparing anti-inflammatory phenyl-lower-alkylamines
-
N-{3- and 4-[R1 -(phenyl)-C(=X)]-phenyl-lower-alkyl}amines, useful as anti-inflammatory agents, are prepared either by reduction of 3- or 4-[R1 -(phenyl)-CO]-phenyl-lower-alkanoylamines, which are also useful as anti-inflammatory agents; by benzoylating a phenyl-lower-alkylamine; by reaction of a 3- or 4-lithiophenyl-lower-alkylamine with a R1 -(phenyl)-carboxaldehyde, a R1 -(phenyl)-lower-alkyl ketone or a R1 -(phenyl)-carbonitrile or by transformations involving manipulations of a carbonyl or carbinol group.
- -
-
-
- 1-Acyl-3-(amino-lower-alkyl)indoles
-
1-Acyl-3-(amino-lower-alkyl)indoles, useful as anti-inflammatory agents, are prepared either by acylation of a 3-(amino-lower-alkyl)indole; by Fisher indole synthesis from an N'-acylphenylhydrazine and an amino-lower-alkanone; by alkylation of an amine with a 1-acyl-3-(halo-lower-alkyl)indole; or by reductive alkylation of a 1-acyl-3-indole-lower-alkylcarboxaldehyde.
- -
-
-
- Anti-inflammatory phenyl-lower-alkylamines
-
N-{3-[R1 -(phenyl)-C(=X)]-phenyl-lower-alkyl}amines having anti-inflammatory utility are prepared either by reduction of a 3-[R1 -(phenyl)-CO]-phenyl-lower-alkanoylamine; by benzoylating a phenyl-lower-alkylamine; by reaction of a 3-lithiophenyl-lower-alkylamine with a R1 -(phenyl)-carboxaldehyde, a R1 -(phenyl)lower-alkyl ketone or a R1 -(phenyl)-carbonitrile or by transformations involving manipulations of a carbonyl or carbinol group.
- -
-
-
- 2-Naphthyl-lower-alkylamines
-
2-Naphthyl-lower-alkylamines, useful as anti-inflammatory agents, are prepared by reaction of a 2-naphthyl-lower-alkanoyl halide with an amine and reduction of the resulting 2-naphthyl-lower-alkanoylamine with a reagent effective to reduce an amide to an amine.
- -
-
-
- 3-(Piperidino-lower-alkyl)-indoles
-
1-Acyl-3-(amino-lower-alkyl)indoles, useful as anti-inflammatory agents, are prepared either by acylation of a 3-(amino-lower-alkyl)indole; by Fisher indole synthesis from an N'-acylphenylhydrazine and an amino-lower-alkanone; by alkylation of an amine with a 1-acyl-3-(halo-lower-alkyl)indole; or by reductive alkylation of a 1-acyl-3-indole-lower-alkylcarboxaldehyde.
- -
-
-
- Phenyl-lower-alkylamines
-
Phenyl-lower-alkylamines having anti-inflammatory activity are prepared either by reductive alkylation of an amine with a phenyl-lower-alkanaldehyde; by condensation of a phenyl-lower-alkanaldehyde with a secondary amine, conversion of the resulting phenylvinylamine to the corresponding iminium salt, and reduction of the latter with an alkali metal borohydride; or by reaction of a phenyl-lower-alkanoyl halide with an amine and reduction of the resulting amide with a reagent effective to reduce an amide to an amine.
- -
-
-