- Direct Synthesis of Ketones from Methyl Esters by Nickel-Catalyzed Suzuki–Miyaura Coupling
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The direct conversion of alkyl esters to ketones has been hindered by the sluggish reactivity of the starting materials and the susceptibility of the product towards subsequent nucleophilic attack. We have now achieved a cross-coupling approach to this transformation using nickel, a bulky N-heterocyclic carbene ligand, and alkyl organoboron coupling partners. 65 alkyl ketones bearing diverse functional groups and heterocyclic scaffolds have been synthesized with this method. Catalyst-controlled chemoselectivity is observed for C(acyl)?O bond activation of multi-functional substrates bearing other bonds prone to cleavage by Ni, including aryl ether, aryl fluoride, and N-Ph amide functional groups. Density functional theory calculations provide mechanistic support for a Ni0/NiII catalytic cycle and demonstrate how stabilizing non-covalent interactions between the bulky catalyst and substrate are critical for the reaction's success.
- Daneshfar, Omid,Hong, Xin,Houk, Kendall N.,Newman, Stephen G.,Xie, Pei-Pei,Zheng, Yan-Long
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supporting information
p. 13476 - 13483
(2021/05/10)
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- Ligand-Controlled Chemoselective C(acyl)-O Bond vs C(aryl)-C Bond Activation of Aromatic Esters in Nickel Catalyzed C(sp2)-C(sp3) Cross-Couplings
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A ligand-controlled and site-selective nickel catalyzed Suzuki-Miyaura cross-coupling reaction with aromatic esters and alkyl organoboron reagents as coupling partners was developed. This methodology provides a facile route for C(sp2)-C(sp3) bond formation in a straightforward fashion by successful suppression of the undesired β-hydride elimination process. By simply switching the phosphorus ligand, the ester substrates are converted into the alkylated arenes and ketone products, respectively. The utility of this newly developed protocol was demonstrated by its wide substrate scope, broad functional group tolerance and application in the synthesis of key intermediates for the synthesis of bioactive compounds. DFT studies on the oxidative addition step helped rationalizing this intriguing reaction chemoselectivity: whereas nickel complexes with bidentate ligands favor the C(aryl)-C bond cleavage in the oxidative addition step leading to the alkylated product via a decarbonylative process, nickel complexes with monodentate phosphorus ligands favor activation of the C(acyl)-O bond, which later generates the ketone product.
- Chatupheeraphat, Adisak,Liao, Hsuan-Hung,Srimontree, Watchara,Guo, Lin,Minenkov, Yury,Poater, Albert,Cavallo, Luigi,Rueping, Magnus
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supporting information
p. 3724 - 3735
(2018/03/21)
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- Nickel-Catalyzed Alkoxy–Alkyl Interconversion with Alkylborane Reagents through C?O Bond Activation of Aryl and Enol Ethers
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A nickel-catalyzed alkylation of polycyclic aromatic methyl ethers as well as methyl enol ethers with B-alkyl 9-BBN and trialkylborane reagents that involves the cleavage of stable C(sp2)?OMe bonds is described. The transformation has a wide substrate scope and good chemoselectivity profile while proceeding under mild reaction conditions; it provides a versatile way to form C(sp2)?C(sp3) bonds that does not suffer from β-hydride elimination. Furthermore, a selective and sequential alkylation process by cleavage of inert C?O bonds is presented to demonstrate the advantage of this method.
- Guo, Lin,Liu, Xiangqian,Baumann, Christoph,Rueping, Magnus
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supporting information
p. 15415 - 15419
(2016/12/03)
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- Enantioselective Suzuki cross-couplings of unactivated 1-fluoro-1-haloalkanes: Synthesis of chiral β-, γ-, δ-, and ε-fluoroalkanes
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The incorporation of fluorine atom into a stereogenic center is a highly challenging transformation with current methodologies offering access mainly to chiral α- and β-fluoroalkanes. In this article, the development of a novel general approach to constru
- Jiang, Xiaojian,Gandelman, Mark
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supporting information
p. 2542 - 2547
(2015/03/04)
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- An efficient approach to mechanically planar chiral rotaxanes
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We describe the first method for production of mechanically planar chiral rotaxanes in excellent enantiopurity without the use of chiral separation techniques and, for the first time, unambiguously assign the absolute stereochemistry of the products. This proof-of-concept study, which employs a chiral pool sugar as the source of asymmetry and a high-yielding active template reaction for mechanical bond formation, finally opens the door to detailed investigation of these challenging targets.
- Bordoli, Robert J.,Goldup, Stephen M.
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supporting information
p. 4817 - 4820
(2014/04/17)
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- Carboxylation of alkylboranes by N-heterocyclic carbene copper catalysts: Synthesis of carboxylic acids from terminal alkenes and carbon dioxide
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Caught in the act: N-Heterocyclic carbene copper(I) complexes (1; IPr=1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) serve as an excellent catalyst for the carboxylation of alkylboranes (2; R=alkyl) with CO2 to afford a variety of functionalized carboxylic acids (3) in high yields. A novel copper methoxide/alkylborane adduct (A) and its subsequent CO2 insertion product (B) have been isolated and shown to be true active catalyst species.
- Ohishi, Takeshi,Zhang, Liang,Nishiura, Masayoshi,Hou, Zhaomin
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p. 8114 - 8117
(2011/10/18)
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- Stereoconvergent amine-directed alkyl-alkyl Suzuki reactions of unactivated secondary alkyl chlorides
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A new family of stereoconvergent cross-couplings of unactivated secondary alkyl electrophiles has been developed, specifically, arylamine-directed alkyl-alkyl Suzuki reactions. This represents the first such investigation to be focused on the use of alkyl
- Lu, Zhe,Wilsily, Ashraf,Fu, Gregory C.
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supporting information; experimental part
p. 8154 - 8157
(2011/07/08)
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- Catalytic asymmetric γ-alkylation of carbonyl compounds via stereoconvergent suzuki cross-couplings
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With the aid of a chiral nickel catalyst, enantioselective γ- (and I-) alkylations of carbonyl compounds can be achieved through the coupling of γ-haloamides with alkylboranes. In addition to primary alkyl nucleophiles, for the first time for an asymmetric cross-coupling of an unactivated alkyl electrophile, an arylmetal, a boronate ester, and a secondary (cyclopropyl) alkylmetal compound are shown to couple with significant enantioselectivity. A mechanistic study indicates that cleavage of the carbon-halogen bond of the electrophile is irreversible under the conditions for asymmetric carbon-carbon bond formation.
- Zultanski, Susan L.,Fu, Gregory C.
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supporting information; experimental part
p. 15362 - 15364
(2011/11/11)
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- Alkyl-alkyl Suzuki cross-coupling of unactivated secondary alkyl chlorides
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No such thing as a problem substrate! In a reaction designed specifically for the title substrates C-C coupling with alkyl boranes occurred in good yield at room temperature with commercially available catalyst components (see scheme). This versatile method is also suitable for Suzuki reactions of secondary and primary alkyl bromides and iodides, as well as primary alkyl chlorides.
- Lu, Zhe,Fu, Gregory C.
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supporting information; experimental part
p. 6676 - 6678
(2010/11/05)
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- High yielding alkylations of unactivated sp3 and sp2 centres with alkyl-9-BBN reagents using an NHC-based catalyst: Pd-PEPPSI-IPr
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High yielding, room temperature cross couplings of unactivated alkyl bromides and aryl bromides/chlorides with alkyl-9-BBN reagents has been achieved using an NHC-based catalyst (Pd-PEPPSI-IPr) via a general, functional-group tolerant and easily implemented protocol. The Royal Society of Chemistry.
- Valente, Cory,Baglione, Sylvia,Candito, David,O'Brien, Christopher J.,Organ, Michael G.
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p. 735 - 737
(2008/09/17)
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- Phosphaadamantanes as ligands for palladium catalyzed cross-coupling chemistry: Library synthesis, characterization, and screening in the Suzuki coupling of alkyl halides and tosylates containing β-hydrogens with boronic acids and alkylboranes
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A 15-member library of phosphaadamantane ligands has been prepared via P-arylation of 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phosphaadamantane. Screening of this tertiary phosphine collection has allowed for the rapid determination of the most suitable ligand, specifically 1,3,5,7-tetramethyl-6-(2,4- dimethoxyphenyl)-2,4,8-trioxa-6-phosphaadamantane, for facilitating Suzuki-type couplings of alkyl halides or tosylates containing β-hydrogens with either boronic acids or alkylboranes.
- Brenstrum, Tim,Gerristma, David A.,Adjabeng, George M.,Frampton, Christopher S.,Britten, James,Robertson, Alan J.,McNulty, James,Capretta, Alfredo
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p. 7635 - 7639
(2007/10/03)
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- A method for palladium-catalyzed cross-couplings of simple alkyl chlorides: Suzuki reactions catalyzed by [Pd2(dba)3]/PCy3
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The window of reactivity is relatively narrow in the first Suzuki cross-coupling of alkyl chlorides with alkyl 9-borabicyclo[3.3.1]nonane (9-BBN) derivatives catalyzed by [Pd2(dba)3] [Eq. (1); dba = (E,E)-dibenzylideneacetone]: whereas good yields are obtained with the ligand tricyclohexylphosphane for ligands that are appreciably larger or smaller, essentially no coupling is observed. As the conditions are compatible with a variety of functional groups, this method introduces a new class of substrates into the family of potential partners in palladium-catalyzed cross-coupling reactions.
- Kirchhoff, Jan H.,Dai, Chaoyang,Fu, Gregory C.
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p. 1945 - 1947
(2007/10/03)
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