- Access to α-Cyano Carbonyls Bearing a Quaternary Carbon Center by Reductive Cyanation
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Reductive cyanation of tertiary alkyl bromides using electrophilic cyanating reagent and zinc reductant was developed, providing various α-cyano ketones, esters, and carboxamides containing a nitrile-bearing all-carbon quaternary center in good to excellent yields under mild reaction conditions. The corresponding reaction mechanism involving in situ generated organozinc reagent and reactivity distinction was elucidated by density functional theory computation.
- Ren, Xinyi,Shen, Chaoren,Wang, Guangzhu,Shi, Zhanglin,Tian, Xinxin,Dong, Kaiwu
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p. 2527 - 2532
(2021/05/05)
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- Asymmetric Hydroacylation Involving Alkene Isomerization for the Construction of C3-Chirogenic Center
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A new transformation pattern for enantioselective intramolecular hydroacylation has been developed involving an alkene isomerization strategy. Proceeding through a five-membered rhodacycle intermediate, 3-enals were converted to C3- or C3,C5-chirogenic cyclopentanones with satisfactory yields, diastereoselectivities, and enantioselectivities. A catalytic cycle has been theoretically calculated and the origin of the stereoselection is rationally explained.
- Liu, Chong,Yuan, Jing,Zhang, Zhenfeng,Gridnev, Ilya D.,Zhang, Wanbin
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supporting information
p. 8997 - 9002
(2021/03/16)
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- Selective Synthesis of β-Ketonitriles via Catalytic Carbopalladation of Dinitriles
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A practical, convenient, and highly selective method of synthesizing β-ketonitriles from the Pd-catalyzed addition of organoboron reagents to dinitriles has been developed. This method provides excellent functional-group tolerance, a broad scope of substrates, and the convenience of using commercially available substrates. The method is expected to show further utility in future synthetic procedures.
- Zeng, Ge,Liu, Jichao,Shao, Yinlin,Zhang, Fangjun,Chen, Zhongyan,Lv, Ningning,Chen, Jiuxi,Li, Renhao
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p. 861 - 867
(2021/01/09)
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- Method for synthesizing beta-ketonitrile and derivatives thereof
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The invention discloses a method for synthesizing beta-ketonitrile and derivatives thereof. The beta-ketonitrile is prepared by a reaction of malononitrile and derivatives thereof with arylboronic acid. According to the invention, reactants are wide in source and low in cost; the reaction is carried out in a solvent, and the solvent is a mixture of toluene and water; in the process of the reaction, a palladium catalyst, an acid additive and a ligand are also added into the solvent; the acidic additive is any one selected from benzenesulfonic acid, p-toluenesulfonic acid, p-nitrobenzenesulfonic acid, trifluoromethanesulfonic acid and trifluoroformic acid; and the ligand is any one selected from 4,4'-dimethyl-2,2'-bipyridyl, 6,6'-dimethyl-2,2'-bipyridyl and 5,5'-dimethyl-2,2'-bipyridyl. The method in the invention can directly synthesize the target product in one step, does not need to separate an intermediate product, can obtain the target product only by a stirring reaction under normal pressure, has the highest yield of 98%, is especially suitable for synthesis of beta-ketonitrile derivatives sensitive to alkaline conditions, and provides better guarantee for development of organic compounds related to beta-ketonitrile derivatives.
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Paragraph 0066-0070
(2021/04/21)
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- Rhodium-Catalyzed Addition of Aryl Boronic Acids to 2,2-Disubstituted Malononitriles
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β-Ketonitriles bearing a quaternary carbon at the 2-position were prepared through Rh-catalyzed addition of aryl boronic acids to 2,2-disubstituted malononitriles. In contrast to the previously described transnitrilative cyanation of aryl boronic acids with dialkylmalononitriles, the present reaction avoids retro-Thorpe collapse of the intermediate addition product through the use of a milder base. The reaction was amenable to a variety of aryl boronic acids and disubstituted malononitriles, providing a diverse array of β-ketonitriles. The products could be further derivatized to valuable chiral α,α-disubstituted-β-aminonitriles through addition reactions to the corresponding N-tert-butanesulfinyl imines.
- Malapit, Christian A.,Caldwell, Donald R.,Luvaga, Irungu K.,Reeves, Jonathan T.,Volchkov, Ivan,Gonnella, Nina C.,Han, Zhengxu S.,Busacca, Carl A.,Howell, Amy R.,Senanayake, Chris H.
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supporting information
p. 6999 - 7002
(2017/06/06)
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- Electrophilic Cyanation of Boron Enolates: Efficient Access to Various β-Ketonitrile Derivatives
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The highly efficient electrophilic cyanation of boron enolates using readily available cyanating reagents, N-cyano-N-phenyl-p-toluenesulfonamide (NCTS) and p-toluenesulfonyl cyanide (TsCN), is reported. Various β-ketonitriles were prepared by this new protocol, which has a remarkably broad substrate scope compared to existing methods. The present method also allowed efficient synthesis of β-ketonitriles containing a quaternary α-carbon center. In addition, a preliminary result with the use of a chiral boron enolate for the enantioselective cyanation reaction is described.
- Kiyokawa, Kensuke,Nagata, Takaya,Minakata, Satoshi
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supporting information
p. 10458 - 10462
(2016/08/24)
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- Variations on the Blaise Reaction: Synthesis of 3,5-Dioxopentanoates and 3-Amino-5-oxopent-3-enoates
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We have achieved a facile and convenient synthesis of a variety of 3,5-dioxopentanoates (3,5-diketo esters) and 3-amino-5-oxopent-3-enoates by a zinc-mediated condensation of readily available 3-oxopropanenitriles (α-cyano ketones) with ethyl bromoacetate. The reaction is a variation on the classical Blaise reaction, tuned to the synthesis of trifunctional compounds having 3,5-diketo ester or 3-enamino 5-keto ester functional groups. Our studies revealed that the Blaise reaction on the nitrile occurs in preference to the Reformatsky reaction on the neighboring ketone when the two functional groups are in a geminal relationship, as found in α-cyano ketones, possibly due to zinc complexation leading to increased electrophilicity of the nitrile.
- Rao, H. Surya Prakash,Muthanna, Nandurka
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supporting information
p. 2014 - 2018
(2016/08/09)
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- Rhodium-Catalyzed Transnitrilation of Aryl Boronic Acids with Dimethylmalononitrile
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An efficient transnitrilation of aryl boronic acids with dimethylmalononitrile (DMMN) is described. This rhodium-catalyzed electrophilic cyanation presents a novel approach to prepare aryl nitriles by using a carbon-bound cyanating reagent which undergoes cross-coupling with the aryl boronic acid. The reaction expands the degree of functional-group compatibility exhibited by the transnitrilation of aryl Grignard and aryllithium reagents. A variety of aryl boronic acid derivatives and dialkylmalononitriles were amenable to the transnitrilation.
- Malapit, Christian A.,Reeves, Jonathan T.,Busacca, Carl A.,Howell, Amy R.,Senanayake, Chris H.
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supporting information
p. 326 - 330
(2016/01/25)
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- Transnitrilation from Dimethylmalononitrile to Aryl Grignard and Lithium Reagents: A Practical Method for Aryl Nitrile Synthesis
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An electrophilic cyanation of aryl Grignard or lithium reagents, generated in situ from the corresponding aryl bromides or iodides, by a transnitrilation with dimethylmalononitrile (DMMN) was developed. DMMN is a commercially available, bench-stable solid. The transnitrilation with DMMN avoids the use of toxic reagents and transition metals and occurs under mild reaction conditions, even for extremely sterically hindered substrates. The transnitrilation of aryllithium species generated by directed ortho-lithiation enabled a net C-H cyanation. The intermediacy of a Thorpe-type imine adduct in the reaction was supported by isolation of the corresponding ketone from the quenched reaction. Computational studies supported the energetic favorability of retro-Thorpe fragmentation of the imine adduct. (Chemical Equation Presented).
- Reeves, Jonathan T.,Malapit, Christian A.,Buono, Frederic G.,Sidhu, Kanwar P.,Marsini, Maurice A.,Sader, C. Avery,Fandrick, Keith R.,Busacca, Carl A.,Senanayake, Chris H.
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supporting information
p. 9481 - 9488
(2015/08/11)
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- Chemoselective efficient synthesis of functionalized β-oxonitriles through cyanomethylation of Weinreb amides
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A synthesis of β-oxonitriles is reported via the generation of R1R2CLiCN species followed by the trapping with variously decorated Weinreb amides. The optimization study revealed that lithiation of acetonitriles is best accomplished by deprotonation with MeLi-LiBr at low temperature. The protocol can be conveniently adapted to the synthesis of α-mono or α,α-disubstituted cyanoketones. 15N- and 17O-NMR data are reported for selected compounds. This journal is
- Mamuye, Ashenafi Damtew,Castoldi, Laura,Azzena, Ugo,Holzer, Wolfgang,Pace, Vittorio
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supporting information
p. 1969 - 1973
(2015/03/05)
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- Palladium-catalyzed carbonylative α-arylation to β-ketonitriles
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A carbonylative α-arylation process employing unactivated nitriles for the first time is described. The reaction tolerates a range of (hetero)aryl iodides and several nitrile coupling partners. No prefunctionalization of the nitriles is necessary and the resulting β-ketonitriles are obtained in good to excellent yields. The methodology also allows for a convenient 13C-labelling of the generated carbonyl moiety. Three COmponent α-arylation: A carbonylative α-arylation process employing nitriles for the first time is described (see scheme). The reaction tolerates a range of (hetero)aryl iodides and several nitrile coupling partners. No prefunctionalization of the nitriles is necessary and the resulting β-ketonitriles are obtained in good to excellent yields. In addition, the methodology allows for a 13C-labelling of the generated carbonyl moiety.
- Schranck, Johannes,Burhardt, Mia,Bornschein, Christoph,Neumann, Helfried,Skrydstrup, Troels,Beller, Matthias
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supporting information
p. 9534 - 9538
(2014/08/18)
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- Carbopalladation of nitriles: Synthesis of benzocyclic ketones and cyclopentenones via Pd-catalyzed cyclization of ω-(2-iodoaryl)alkanenitriles and related compounds
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An efficient procedure for the synthesis of 2,2-disubstituted benzocyclic ketones by intramolecular carbopalladation of nitriles has been developed. The cyclization of substituted 3-(2-iodoaryl)-propanenitriles affords indanones in high yields. The reaction is compatible with a wide variety of functional groups. This methodology has been extended to the synthesis of tetralones and cyclopentenones.
- Pletnev, Alexandre A.,Larock, Richard C.
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p. 9428 - 9438
(2007/10/03)
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- Synthesis of benzocyclic ketones via palladium-catalyzed cyclization of ω-(2-iodoaryl)alkanenitriles
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An efficient procedure for the synthesis of 2,2-disubstituted benzocyclic ketones by intramolecular carbopalladation of nitriles has been developed. The cyclization of substituted 3-(2-iodoaryl)propanenitriles affords indanones in high yields. The reactio
- Pletnev, Alexandre A.,Larock, Richard C.
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p. 2133 - 2136
(2007/10/03)
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- The reaction of 2-(tetrazol-5-yl)alkyl ketones and of 2-(tetrazol-5-yl)alkanoic acid derivatives with lead tetraacetate. A novel method of preparation of alk-2-ynyl ketones and alk-2-ynoic acid derivatives
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The majority of tetrazolylacetyl derivatives 2 and 7, when treated with lead tetraacetate in dry 1,4-dioxane at room or lower temperature, are oxidized with elimination of molecular nitrogen mainly to the corresponding alkynoyl derivatives 4 and 8, respectively. Vinylidenes (25) have been shown to be the intermediates of the reaction. The reaction does not take place when either the tetrazolyl group is N-substituted or the carbon atom separating the tetrazolyl and the carbonyl groups is disubstituted or these two groups are separated by two carbon atoms as in compound 17. The reaction offers a convenient method for the conversion of 2-cyanoacetyl derivatives into alk-2-ynoyl derivatives via intermediate tetrazolylacetyl derivatives. The 4-methoxyanilide 7o reacts differently, affording the fused heterocyclic compounds 19o and 20o.
- Fetter,Nagy,Giang,Kajtar-Peredy,Rockenbauer,Korecz,Czira
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p. 1131 - 1139
(2007/10/03)
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- Solvent dependent photochemical reactions of 3-(2-alkylphenyl)-2,2- dimethyl-3-oxopropanoates and their related compounds
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Photochemical reactions of methyl 3-(o-alkylphenyl)-2,2-dimethyl-3- oxopropanoates in hexane gave only the corresponding benzocyclobutenols. However, when irradiation was carried out in methanol, 3-oxonaphthalenones were produced together with the benzocyclobutenols. The ratio of benzocyclobutenol to naphthalenone depends on the bulkiness of the alkyl group in the ortho position. Intermediary 1,4-diradicals or dienols were efficiently trapped by oxygen to afford the corresponding peroxides and/or oxygenated compounds derived from the peroxides.
- Saito, Masaichi,Kamei, Yumiko,Kuribara, Kanae,Yoshioka, Michikazu,Hasegawa, Tadashi
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p. 9013 - 9018
(2007/10/03)
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- Phase-Transfer Catalyzed Formation of α-Cyano Ketones from Ketone Aroylhydrazones in NaCN(aq)-Inert Organic Solvent System
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α-Cyanoalkyl aryl ketones can be obtained from ketone aroylhydrazones by heterogeneous reaction with aqueous sodium cyanide, an inert organic solvent, and acetic acid in the presence of air and a catalytic amount of a quaternary ammonium salt.The initiall
- Chiba, Toshiro,Okimoto, Mitsuhiro
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p. 6163 - 6166
(2007/10/02)
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- MESOMERIC ANIONS. X. METHYLATION OF ALKALI-METAL DERIVATIVES OF SOME 1,3-KETONITRILES
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The effect of polar factors on the relative nucleophilicity of the oxygen and carbon reaction centers in the alkali-metal derivatives of 2-(X-benzoyl)acetonitriles, 2-(X-benzoyl)propionitriles, and 2-(X-phenyl)acetylacetonitriles was investigated.During methylation with methyl iodide and methyl p-toluenesulfonate in DMFA the ratio of the C- and O-methylation products for all the investigated compounds decreases with increase in the accepting power of the substituent X.It was shown that the sensitivity of the C-reaction center to the effect of the substituent X is greater than that of the O-center.
- Emelina, E. E.,Ershov, B. A.
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p. 692 - 696
(2007/10/02)
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- Photochemistry of the Carbon-Nitrogen Double Bond. Part 2. An Investigation of the 3-Methylenepropan-1-imine and 3-Oxopropan-1-imine Chromophores
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The synthesis of the non-conjugated imino compounds N-methoxy-2,2,4-trimethyl-1-phenylpent-3-en-1-imine (8), N-methoxy-2,2-dimethyl-4,4-diphenylbut-3-en-1-imine (9), 2-(1,1-dimethyl-3,3-diphenylprop-2-enyl)-4,4-dimethyl-4,5-dihydro-oxazole (10), and 2-ben
- Pratt, Albert C.,Abdul-Majid, Qais
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p. 359 - 364
(2007/10/02)
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- MESOMERIC ANIONS IX. MECHANISM AND LAWS OF ALKYLATION OF ALKALI-METAL DERIVATIVES OF 2-BENZOYLPROPIONITRILE
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The quantitative relationship governing the alkylation of ambident nucleophiles (alkali-metal derivatives of 2-benzoylpropionitrile) by alkyl halides RY (R = Me, Et, i-Pr, Y = Cl, Br, I) and methyl p-toluenesulfonate in hexamethylphosphorotriamide and dimethylformamide were investigated.The ratio of the C- and O-alkylation products does not depend on the concentration of the ambident enolate or the nature of the cation; it decreases with increase in the "hardness" of the leaving group of the alkylation agent and with increase in the size of the alkyl group.Conductometric investigation of the conductivity of solutions of the sodium and potassium derivatives of 2-benzoylpropionitrile in dimethylformamide showed that in the range of 0 - 40 deg C they are dissociated to the extent of 40 - 95percent.The methylation rate only depends on the concentration of the "free" anion.The activation parameters were determined, and the mechanism of the process is discussed.
- Emelina, E. E.,Ershov, B. A.
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p. 1820 - 1825
(2007/10/02)
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- Electroreduction of Organic Compounds, 1. - Condensation Reactions of Acetonitrile with the Aid of Electrogenerated Bases
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Electrochemical reduction of alkyl benzoates in dry acetonitrile yields benzoylacetonitrile (2).Methyl 3-cyano-2-hydroxy-2-phenylpropionate (7) is obtained from methyl phenylglyoxalate (5) under the same conditions. - Analogously β-dialkylaminocinnamonitriles 9 can be obtained from N,N-dialkylthiobenzamides 8.N,N-Dimethylbenzamide (10) yields β-dimethylamino-cinnammonitrile (9a) on electroreduction in the presence of azobenzene as a probase by catalytical generation of acetonitrile anions.
- Kistenbruegger, Lothar,Mischke, Peter,Voss, Juergen,Wiegand, Gabriele
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p. 461 - 471
(2007/10/02)
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