- The copper-catalysed Suzuki-Miyaura coupling of alkylboron reagents: disproportionation of anionic (alkyl)(alkoxy)borates to anionic dialkylborates prior to transmetalation
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We report the first example of CuI-catalysed coupling of alkylboron reagents with aryl and heteroaryl iodides that affords products in good to excellent yields. Preliminary mechanistic studies with alkylborates indicate that the anionic (alkoxy)(alkyl)borates, generated from alkyllithium and alkoxyboron reagents, undergo disproportionation to anionic dialkylborates and that both anionic alkylborates are active for transmetalation to a CuI-catalyst. Results from a radical clock experiment and the Hammett plot imply that the reaction likely proceeds via a non-radical pathway.
- Basnet, Prakash,Thapa, Surendra,Dickie, Diane A.,Giri, Ramesh
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- 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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- Palladium-Catalyzed Carbonylative Cross-Coupling of Difluoroalkyl Halides with Alkylboranes under 1 atm of CO
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A palladium catalyzed carbonylative cross-coupling of difluoroalkyl halides with alkyl-9-BBN under 1 atm of CO has been developed. The reaction shows broad substrate scope and high functional group tolerance, even toward complex pharmaceuticals, providing
- Zhang, Xingang,Zhao, Hai-Yang,Zhou, Minqi
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supporting information
p. 9106 - 9111
(2021/12/06)
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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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- Switchable Selectivity in the Pd-Catalyzed Alkylative Cross-Coupling of Esters
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The Pd-catalyzed cross-coupling of phenyl esters and alkyl boranes is disclosed. Two reaction modes are rendered accessible in a selective fashion by interchange of the catalyst. With a Pd-NHC system, alkyl ketones can be prepared in good yields via a Suzuki-Miyaura reaction proceeding by activation of the C(acyl)-O bond. Use of a Pd-dcype catalyst enables alkylated arenes to be synthesized by a modified pathway with extrusion of CO. Applications of this divergent coupling strategy and the origin of the switchable selectivity are discussed.
- Masson-Makdissi, Jeanne,Vandavasi, Jaya Kishore,Newman, Stephen G.
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supporting information
p. 4094 - 4098
(2018/07/15)
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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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- Efficient synthesis of secondary alkyl fluorides via suzuki cross-coupling reaction of 1-halo-1-fluoroalkanes
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Organofluorine compounds have found extensive applications in various areas of science. Consequently, the development of new efficient and selective methods for their synthesis is an important goal in organic chemistry. Here, we present the first Suzuki c
- Jiang, Xiaojian,Sakthivel, Sekarpandi,Kulbitski, Kseniya,Nisnevich, Gennady,Gandelman, Mark
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supporting information
p. 9548 - 9551
(2014/07/22)
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- Preparation of imides via the palladium-catalyzed coupling reaction of organoborons with methyl N -[methoxy(methylthio)methylene]carbamate as a one-carbon elongation reaction
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The preparation of imides via the palladium-catalyzed coupling reaction as a one-carbon elongation reaction is described. The palladium-catalyzed coupling reaction of aryl-, alkyl-, and alkenylborons with N-[methoxy(methylthio) methylene]carbamate in the presence of Cu(I) thiophene-2-carboxylate (CuTC) affords imino ethers that are converted to the corresponding imides by acidic hydrolysis in high yield. The imino ethers are also useful for preparing the corresponding ester without using carbon monoxide.
- Tomizawa, Takuhei,Orimoto, Kohei,Niwa, Takashi,Nakada, Masahisa
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supporting information
p. 6294 - 6297
(2013/02/23)
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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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- Copper-catalyzed cross-coupling reaction of organoboron compounds with primary alkyl halides and pseudohalides
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Non-activated alkyl electrophiles, including alkyl iodides, bromides, tosylates, mesylates, and even chlorides, underwent copper-catalyzed cross-coupling with aryl boron compounds and alkyl 9-BBN reagents (see scheme; 9-BBN=9-borabicyclo[3.3.1]nonane). The reactions proceed with practically useful reactivities and thus complement palladium- and nickel-catalyzed Suzuki-Miyaura coupling reactions of alkyl halides.
- Yang, Chu-Ting,Zhang, Zhen-Qi,Liu, Yu-Chen,Liu, Lei
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supporting information; experimental part
p. 3904 - 3907
(2011/05/15)
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- Asymmetric alkyl-alkyl cross-couplings of unactivated secondary alkyl electrophiles: Stereoconvergent suzuki reactions of racemic acylated halohydrins
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A method for asymmetric alkyl-alkyl Suzuki reactions of unactivated secondary alkyl electrophiles, specifically, cross-couplings of racemic acylated halohydrins with alkylborane reagents, has been developed. A range of protected bromohydrins, as well as a protected chlorohydrin and a homologated bromohydrin, are coupled in good ee by a catalyst derived from commercially available components.
- Owston, Nathan A.,Fu, Gregory C.
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supporting information; experimental part
p. 11908 - 11909
(2010/11/04)
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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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- 2-substituted benzo[b]furans from (E)-1,2-dichlorovinyl ethers and organoboron reagents: Scope and mechanistic investigations into the one-pot Suzuki coupling/direct arylation
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2-Substituted benzo[b]furans can easily be assembled from simple phenols, boronic acids or other organoboron reagents, and trichloroethylene. The overall process requires only two synthetic steps, with the key step being a one-pot sequential Suzuki cross-coupling/direct arylation reaction. The method tolerates many useful functional groups and does not require the installation of any other activating functionality. The modular nature of the process permits the rapid synthesis of many analogues using essentially the same chemistry, of particular value in drug development. Results of kinetic isotope effect studies and investigations into the regioselectivity of the process indicate that the direct arylation step most likely does not involve an electrophilic palladation. The most likely mechanism lies somewhere on the continuum between a C-H bond metathesis and an assisted palladation or concerted metallation-deprotonation pathway. A very efficient modular approach to the construction of benzo[b]furans using trichloroethylene as a scaffold is described. This method gives easy access to highlysubstituted heterocycles in only two synthetic operations, and is especially suitable for rapid construction of compound libraries.
- Geary, Laina M.,Hultin, Philip G.
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supporting information; scheme or table
p. 5563 - 5573
(2010/12/29)
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- Utilization of potassium vinyltrifluoroborate in the development of a 1,2-dianion equivalent
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Previous studies of orthogonally reactive dibora species led to the discovery of a unique reactivity pattern associated with potassium vinyltrifluoroborate. Upon hydroboration, the vinyltrifluoroborate generates a 1,2-diboraethane, which is distinct from
- Molander, Gary A.,Sandrock, Deidre L.
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scheme or table
p. 2369 - 2372
(2009/11/30)
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- Enantioselective alkyl-alkyl suzuki cross-couplings of unactivated homobenzylic halides
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The first effective method for asymmetric cross-couplings of unactivated alkyl electrophiles has been developed, specifically, a nickel-based catalyst for stereoconvergent Suzuki reactions of homobenzylic bromides with alkylboranes. To the best of our knowledge, there are no previous examples of enantioselective Suzuki couplings of alkyl electrophiles (activated or unactivated). Both of the catalyst components are commercially available. Copyright
- Saito, Bunnai,Fu, Gregory C.
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p. 6694 - 6695
(2008/12/22)
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- Potential modes of interaction of 9-aminomethyl-9,10-dihydroanthracene (AMDA) derivatives with the 5-HT2A receptor: A ligand structure-affinity relationship, receptor mutagenesis and receptor modeling investigation
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The effects of 3-position substitution of 9-aminomethy 1-9,10- dihydroanthracene (AMDA) on 5-HT2A receptor affinity were determined and compared to a parallel series of DOB-like 1-(2,5-dimethoxyphenyl)-2- aminopropanes substituted at the 4-position. The results were interpreted within the context of 5-HT2A receptor models that suggest that members of the DOB-like series can bind to the receptor in two distinct modes that correlate with the compounds' functional activity. Automated ligand docking and molecular dynamics suggest that all of the AMDA derivatives, the parent of which is a 5-HT2A antagonist, bind in a fashion analogous to that for the sterically demanding antagonist DOB-like compounds. The failure of the F340 6.52L mutation to adversely affect the affinity of AMDA and the 3-bromo derivative is consistent with the proposed modes of orientation. Evaluation of ligand-receptor complex models suggest that a valine/threonine exchange between the 5-HT2A and D2 receptors may be the origin of selectivity for AMDA and two substituted derivatives.
- Runyon, Scott P.,Mosier, Philip D.,Roth, Bryan L.,Glennon, Richard A.,Westkaemper, Richard B.
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experimental part
p. 6808 - 6828
(2009/10/17)
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- 1-[4-(3-Phenylalkyl)phenyl]-2-aminopropanes as 5-HT(2A) partial agonists
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Phenylalkylamines such as 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane (DOB; 1a) and its corresponding iodo derivative DOI (2) are commonly used 5-HT2 serotonin agonists. Previous studies have established that the 2,5-dimethoxy substitution p
- Dowd,Herrick-Davis,Egan,DuPre,Smith,Teitler,Glennon
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p. 3074 - 3084
(2007/10/03)
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- Synthesis of η-arene derivatives of chromium and molybdenum containing Lewis-acid boron substituents
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The compounds Ph(CH2)3B(OH)2 I, [Ph(CH2)3BO]3 II, Ph(CH2)3B(1,2-O2C6H4) III, Ph(CH2)3BC8H14 IV (BC8H14 = 9-borabicyclo[3.3.1]nonan-9-yl), [Cr{η-Ph(CH2)3B(1,2-O2C6H 4)}(CO)3] 1, [Cr{η-Ph(CH2)3BC8H14}(CO) 3] 2, [Cr{η-Ph(CH2)3BBr2·SMe 2}(CO)3] 3, [Cr{η-Ph(CH2)4BC8H14}(CO) 3] 4, [Cr(η-Ph(CH2)4BC8H14}(CO) 2(PPh3)] 5, [Cr{η-PhCH2CH=CH2}(CO)3] 6, [Cr{η-Ph(CH2)2CH=CH2}(CO)3] 7, [Cr{η-Ph(CH2)2η-CH=CH2}(CO) 2] 8, [Cr{η-Ph(CH2)2CH=CH2}(CO) 2(PPh3)] 9, [Li(Et2O)n][Cr{η-PhCH2CH=CH 2}(CO)2{C(O)Ph}] 10, [Li(Et2O)n][Cr{η-Ph(CH2) 2CH=CH2}(CO)2{C(O)Ph}] 11, [Mo{η-Ph(CH2)3BC8H14} 2] 12 and [Cr{η-Ph(CH2)3BOC8H14}(CO) 3] 13, have been prepared and characterised. Compounds 1-5, 12 and 13 have π-donor η-arene ligands which also bear a Lewis-acid α-acceptor boron group. There was no evidence that these boron groups formed ground-state intra- or inter-molecular interactions with the Lewis base functions of the carbonyl oxygen atoms.
- Green, Malcolm L. H.,Wagner, Matthias
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p. 2467 - 2473
(2007/10/03)
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