Categories: C-C Bond Formation > Arenes >
Synthesis of aryl ketones
Stable and non-hygroscopic aluminum dodecatungstophosphate (AlPW12O40), which is prepared easily from cheap and commercially available compounds, is an effective catalyst for Friedel-Crafts acylation reactions using carboxylic acids, acetic anhydride and benzoyl chloride in the absence of solvent under mild reaction conditions.
H. Firouzabadi, N. Iranpoor, F. Nowrouzi, Tetrahedron, 2004, 60, 10843-10850.
A synergistic merger of photoredox, nickel, and hydrogen atom transfer catalysis enables direct aldehyde C-H functionalization. This mild, operationally simple protocol provides a broad range of ketones in excellent yield from commercially available aldehydes, along with aryl or alkyl bromides.
X. Zhang, D. W. C. MacMillan, J. Am. Chem. Soc., 2017, 139, 11353-11356.
The cooperative catalysis of nickel and tetrabutylammonium decatungstate as a hydrogen-atom-transfer photocatalyst enables a cross-coupling of aryl halides and α-bromo acetates with an array of (hetero)aromatic and aliphatic aldehydes to provide a variety of ketones. This method tolerates a broad range of functional groups.
P. Fan, C. Zhang, L. Zhang, C. Wang, Org. Lett., 2020, 22, 3875-3878.
The palladium acetate-catalyzed coupling reaction of aryl boronic acids with carboxylic anhydrides or acyl chlorides was carried out smoothly in water in the presence of PEG or [bmim][PF6] to give high yields of ketones. The Pd(OAc)2-H2O-[bmim][PF6] catalytic system can be recovered and reused.
B. Xin, Yuhong Zhang, K. Cheng, J. Org. Chem., 2006, 71, 5725-5731.
A mechanochemical solvent-free acyl Suzuki-Miyaura cross-coupling enables a highly chemoselective synthesis of ketones from widely available acyl chlorides and boronic acids. This chemoselective acylation reaction is conducted in the solid state, in the absence of potentially harmful solvents, and for a short reaction time.
J. Zhang, P. Zhang, Y. Ma, M. Szostak, Org. Lett., 2022, 24, 2338-2343.
A magnesium amide additive activates and controls the addition of mild Grignard reagents to carboxylate anions and therefore avoids the use of organolithium reagents or activated acyl sources that need to be independently prepared. This strategy enables the modular synthesis of ketones from CO2 and the preparation of isotopically labeled pharmaceutical building blocks in a single operation.
K. Colas, A. C. V. D. dos Santos, A. Mendoza, Org. Lett., 2019, 21, 7851-7856.
[DCPP]n aggregates can act as a versatile visible-light photocatalyst in decarboxylative C-C cross-coupling, amidation, and esterification reactions. In these reactions, [DCPP]n aggregates were formed in situ through physical π-π stacking of DCPP monomers in organic solvents.
M. He, X. Yu, Y. Wang, F. Li, M. Bao, J. Org. Chem., 2021, 86, 5016-5025.
The inexpensive 2-chloro-thioxanthen-9-one as photoredox catalyst mediates the formation of acyl radicals from α-keto acids under visible light illumination. These reactive species added to olefins or coupled with aryl halides via a bipyridyl-stabilized Ni(II) catalyst to provide a diverse range of ketones. This reliable, atom-economical, and eco-friendly protocol tolerates a wide range of functional groups.
D.-L. Zhu, Q. Wu, D. J. Young, H. Wang, Z.-G. Ren, H.-X. Li, Org. Lett., 2020, 22, 6832-6837.
Friedel-Crafts reactions of oxalyl chloride with two arenes provide symmetrical and unsymmetrical diaryl ketones in good yields.
D. F. Taber, M. R. Sethuraman, J. Org. Chem., 2000, 65, 254-255.
Polysilane/alumina-supported palladium nanoparticles catalyze carbonylative Suzuki-Miyaura coupling reactions under atmospheric pressure of CO gas to provide diaryl ketones in excellent yields. The ligand-free immobilized palladium nanoparticles could be recovered by simple filtration and reused.
T. Yasukawa, Z. Zhu, Y. Yamashita, S. Kobayashi, Synlett, 2021, 32, 502-504.
Evaluation of N-acyl-imides, N-acyl-lactams, and N-acyl-oxazolidinones bearing five- and six-membered rings using Pd(II)-NHC and Pd-phosphine systems has revealed the relative reactivity order of N-activating groups in Suzuki-Miyaura cross-coupling. N-Acyl-δ-valerolactams are highly effective precursors for cross-coupling via acyl-metal intermediates.
Md. M. Rahman, D. J. Pyle, E. Bisz, B. Dziuk, K. Ejsmont, R. Lalancette, Q. Wang, H. Chen, R. Szostak, M. Szostak, J. Org. Chem., 2021, 86, 10455-10466.
A combination of site-selective N,N-di-Boc-activation of the amide nitrogen with practical air- and moisture-stable, well-defined, and highly reactive [Pd(NHC)(cin)Cl] enables a general, highly selective method for the room temperature Suzuki-Miyaura cross-coupling to provide biaryl ketones in high yields.
P. Lei, G. Meng, Y. Ling, J. An, S. P. Nolan, M. Szostak, Org. Lett., 2017, 19, 6510-6513.
The commercially available [(IPr)PdCl2(aniline)] complex is a well-defined, air- and moisture-stable catalyst for highly efficient Suzuki-Miyaura cross-coupling of amides, esters, aryl chlorides, and Buchwald-Hartwig amination. The availability of various aniline scaffolds has a significant potential in fine-tuning of challenging cross-couplings by Pd-NHCs.
Q. Xia, S. Shi, P. Gao, R. Lalancette, R. Szostak, M. Szostak, J. Org. Chem., 2021, 86, 15650-15657.
A highly chemoselective Suzuki-Miyaura cross-coupling of trifluoromethanesulfonamides (triflamides) accomplishes a direct synthesis of ketones under mild conditions as a powerful alternative to the Weinreb ketone synthesis.
S. Shi, R. Lalancette, R. Szostak, M. Szostak, Org. Lett., 2019, 21, 1253-1257.
The reaction of different aryl, alkyl, and alkynyl Grignard reagents with N-Boc amides provides a wide range of aryl ketones via chemoselective C(O)-N bond cleavage under catalyst-free conditions. α-Ketoamide was successfully converted to aryl diketones, while α,β-unsaturated amide underwent 1,4-addition followed by C(O)-N bond cleavage to provide diaryl propiophenones.
P. Sureshbabu, S. Azeez, N. Muniyappan, S. Sabiah, J. Kandasamy, J. Org. Chem., 2019, 84, 11823-11838.
The combination of electrocatalysis and nickel catalysis achieves a decarboxylative cross-coupling of four types of α-oxocarboxylic acids and their derivatives with aryl trimethylammonium salts under mild conditions. This strategy enables a practical synthesis of aryl ketones, amides, esters, and aldehydes.
X. Kong, Y. Chen, X. Chen, Z.-X. Lu, W. Wang, S.-F. Ni, Z.-Y. Cao, Org. Lett., 2022, 24, 2137-2142.
N-acylazetidines are bench-stable, readily available amide acylating reagents, in which the reactivity is controlled by amide pyramidalization and strain of the four-membered ring. A general and highly chemoselective synthesis of ketones by the addition of organometallics to N-acylazetidines via stable tetrahedral intermediates offers wide substrate scope and exquisite selectivity for the ketone products.
C. Liu, M. Achtenhagen, M. Szostak, Org. Lett., 2016, 18, 2375-2378.
Pd(OAc)2/PCy3 catalyzes the Hiyama cross-coupling between N-acylglutarimides and arylsiloxanes in the presence of Et3N·3HF and LiOAc to provide the corresponding arylketones in good yields. The reaction had a broad substrate scope and showed good functional group tolerance.
M. A. Idris, S. Lee, Org. Lett., 2020, 22, 9184-9189.
A palladium-catalyzed Suzuki-Miyaura cross-coupling of unconventional amide electrophiles enables a synthesis of sterically hindered ketones via a selective N-C(O) activation. Mechanistic studies demonstrate that steric bulk on the amide has a major impact, which is opposite to the traditional Suzuki-Miyaura cross-coupling of sterically hindered aryl halides.
C. Liu, R. Lalancette, R. Szostak, M. Szostak, Org. Lett., 2019, 21, 7976-7981.
A simple method for the preparation of aryl methyl ketones involves the Pd-catalyzed coupling of commercially available acetyltrimethylsilane with aryl bromides to afford the corresponding acetylated arenes in very good yields. The methodology is tolerant of heterocycles and provides a new method for arene functionalization.
S. D. Ramgren, N. K. Garg, Org. Lett., 2014, 16, 824-827.
A direct acylation of aryl bromides with aldehydes involves palladium-amine cooperative catalysis, affording synthetically important alkyl aryl ketones in good yields in a straightforward manner, and broadening the scope of metal-catalyzed coupling reactions.
J. Ruan, O. Saidi, J. A. Iggo, J. Xiao, J. Am. Chem. Soc., 2008, 130, 10510-10511.
FeCl2 catalyzes a smooth and convenient acylation of functionalized arylzinc halides and benzylic zinc chlorides with various acid chlorides to provide polyfunctionalized diaryl and aryl benzyl ketones.
A. D. Benischke, M. Leroux, I. Knoll, P. Knochel, Org. Lett., 2016, 18, 3626-3629.
Palladium-catalyzed cross-coupling of aryl boronic acids with acyl chlorides at room temperature under phosphine-free conditions affords the corresponding aryl ketones in excellent yields within short times. This synthetic method overcomes common disadvantages of Friedel-Crafts acylation procedures and is compatible with a broad range of acyl chlorides.
A. R. Hajipour, R. Pourkaveh, Synlett, 2014, 25, 1101-1105.
A mild and efficient nickel-catalyzed addition of a broad range of arylboronic acids to alkyl nitriles in a fluorinated solvent provides various aryl ketones in very good yields.
D.-H. Tu, Y. Li, B. Zhao, Y.-J. Gu, B. Wang, J.-Y. Lu, J. Lu, Synlett, 2018, 29, 593-596.
A Ni-catalyzed intermolecular coupling of primary alcohols and organotriflates provides ketones in the presence of acetone. Two competitive oxidation processes, that generate aldehyde in situ via hydrogen transfer oxidation or (pseudo)dehalogenation pathways, are followed by a Ni-catalyzed carbonyl-Heck process.
T. Verheyen, L. van Turnhout, J. K. Vandavasi, E. S. Isbrandt, W. M. De Borggraeve, S. G. Newman, J. Am. Chem. Soc., 2019, 141, 6869-6874.
An array of amides can be cross-coupled with a range of arylboronic acids in very good yields using a commercially available, air- and moisture-stable Pd-PEPPSI-IPr complex as a highly reactive precatalyst in a single, operationally simple protocol. Pd-PEPPSI-IPr provides a significant improvement over all current Pd/phosphane catalysts for amide N-C bond activation.
P. Lei, G. Meng, Y. Ling, J. An, M. Szostak, J. Org. Chem., 2017, 82, 6638-6646.
In a protocol for a nickel-catalyzed alkylation of amides, alkylboranes can be used as nucleophilic partners under mild reaction conditions. The reaction tolereates various functional groups with respect to both coupling partners.
X. Liu, C.-C. Hsiao, L. Guo, M. Rueping, Org. Lett., 2018, 20, 2976-2979.
An NHC-based Pd catalyst enables a Suzuki-Miyaura coupling of aryl esters as electrophiles to provide various ketone-containing products. This contrasts known reactions of similar esters that provide biaryls via nickel catalysis.
T. B. Halima, W. Zhang, I. Yalaoui, X. Hong, Y.-F. Yang, K. N. Houk, S. G. Newman, J. Am. Chem. Soc., 2017, 139, 1311-1318.
An efficient palladium-catalyzed addition of arylboronic acids to aliphatic nitriles provides a broad range of alkyl aryl ketones in good yields. It is noteworthy that sequential addition and intramolecular annulation reactions of 2-(2-hydroxyphenyl)acetonitriles with arylboronic acids smoothly afford 2-arylbenzofurans in good yields under the standard conditions.
X. Wang, X. Wang, M. Liu, J. Ding, J. Chen, H. Wu, Synthesis, 2013, 45, 2241-2244.
A palladium-catalyzed addition of potassium aryltrifluoroborates to aliphatic nitriles leads to a wide range of alkyl aryl ketones with good yields. The scope of the developed approach is successfully explored toward the one-step synthesis of 2-arylbenzo[b]furans via sequential addition and intramolecular annulation reactions. The methodology accepted a wide range of substrates and is applicable to library synthesis.
X. Wang, M. Liu, L. Xu, Q. Wang, J. Chen, J. Ding, H. Wu, J. Org. Chem., 2013, 78, 5273-5281.
A convenient and efficient method allows the synthesis of various arylketones by nickel-catalyzed addition of arylboronic acids to nitriles. A catalytic cycle involving Ni(II) species as the catalytic intermediates is proposed.
Y.-C. Wong, K. Parthasarathy, C.-H. Cheng, Org. Lett., 2010, 12, 1736-1739.
A NiCl2(DME)/dppp/Zn system catalyzed an intermolecular insertion of aryl iodides to nitriles to provide variously substituted arylketone derivatives in good yields with tolerance of a wide variety of functional groups.
J.-C. Hsieh, Y.-C. Chen, A.-Y. Cheng, H.-C. Tseng, Org. Lett., 2012, 14, 1282-1285.
In a palladium-catalyzed one-pot procedure for the synthesis of aryl ketones, triazine esters were coupled with aryl boronic acids to provide aryl ketones in good yields in the presence of 1 mol % Pd(PPh3)2Cl2 for 30 min.
H. Wu, B. Xu, Y. Li, F. Hong, D. Zhu, J. Jian, X. Pu, Z. Zeng, J. Org. Chem., 2016, 81, 2987-2992.
A highly chemoselective, palladium(0)-catalyzed, direct cross-coupling between boronic acids and geometrically activated amides shows excellent functional group tolerance, and delivers the versatile ketone products in high yields. Notably, the method provides direct access to acyl-metal intermediates from sterically distorted, bench-stable amide precursors under mild catalytic conditions.
G. Meng, M. Szostak, Org. Lett., 2015, 17, 4364-4367.
Nickel catalysis and a site-selective N,N-di-Boc activation enable a general Negishi acylation of primary amides. The reaction is promoted by a bench-stable, inexpensive Ni catalyst and shows excellent functional group compatibility.
S. Shi, M. Szostak, Org. Lett., 2016, 18, 5872-5875.
The use of CHCl3 as a convenient and safe carbonyl source in the presence of KOH enables a modular, palladium catalyzed synthesis of aryl(hetero)aryl benzophenones and aryl benzoates from aryl(hetero)aryl halides via an initial carbonylation to generate an aroyl halide, which undergoes coupling with arylboronic acids, boronates, and phenols. Direct carbonylative coupling of indoles at the third position has also been accomplished.
P. Sharma, S. Rohilla, N. Jain, J. Org. Chem., 2017, 82, 1105-1113.
Palladacycles catalyze a carbonylative Suzuki-Miyaura coupling of aryl iodides with arylboronic acids with high turnover numbers and turnover frequencies. Comparison of the palladacycles with a conventional palladium source shows their superiority.
P. Gautam, B. M. Bhanage, J. Org. Chem., 2015, 80, 7810-7815.
Highly selective carbonylative Suzuki reactions of aryl iodides with arylboronic acids using an in situ generated nanopalladium system under ambient conditions and in the absence of an added ligand furnished products in high yields. The addition of pivalic acid can effectively suppress an undesired Suzuki coupling. The synthesis can be easily scaled up, and the catalytic system can be reused up to nine times.
Q. Zhou, S. Wei, W. Han, J. Org. Chem., 2014, 79, 1454-1460.
A palladium(II) chloride catalyzed mild cross-coupling of arylboronic acids with carboxylic anhydrides or acyl chlorides in water in the presence of the inexpensive surfactant sodium dodecyl sulfate (SDS) gives aryl ketones in good yields without the use of phosphine ligands.
B. Xin, Y. Zhang, K. Cheng, Synthesis, 2007, 1970-1978.
A direct cross-coupling reaction of aromatic aldehydes with potassium trifluoro(organo)borates afforded ketones in high yields and under mild conditions in the presence of a rhodium catalyst and acetone.
M. Pucheault, S. Darses, J-P. Genet, J. Am. Chem. Soc., 2004, 126, 15356-15357.
A new palladium-catalyzed cross-coupling reaction between arylboronic acids and mixed anhydrides, generated in situ from carboxylic acids and pivalic anhydride, is presented.
L. J. Goossen, K. Ghosh, Eur. J. Org. Chem., 2002, 3254-3267.
A new Ni catalyst is capable of effecting the rapid cross-coupling of acid fluorides, acid chlorides, acyl cyanides, anhydrides, thioesters, and pyridyl esters with both groups of diorganozinc reagents. Reactions with acid fluorides as electrophilic partners tolerate epimerizable functionality as well as leaving groups.
Y. Zhang, T. Rovis, J. Am. Chem. Soc., 2004, 126, 15964-15965.
A mild and efficient palladium-catalyzed ligand-free decarboxylative coupling of aryl α-keto carboxylic acid with aryl diazonium fluoroborate provides unsymmetrical diaryl ketones in good yields via a radical pathway involving an acyl radical.
S. Panja, P. Maity, B. C. Ranu, J. Org. Chem., 2018, 83, 12609-12618.
Palladium-catalyzed couplings of aryl bromides with N-tert-butylhydrazones as acyl anion equivalents occurs at the C-position to form N-tert-butyl azo compounds. Isomerization of these azo compounds to the corresponding hydrazones, followed by hydrolysis, gave the desired mixed alkyl aryl ketones.
A. Takemiya, J. F. Hartwig, J. Am. Chem. Soc., 2006, 128, 14800-14801.
Pd-catalyzed cross-coupling reaction of acylindium reagents generated in situ from easily available acid chlorides and indium with aryl iodides, triflates and alkenyl triflate enables a reversed-polarity synthesis of various unsymmetric aryl aryl and alkenyl aryl ketones.
D. Lee, T. Ryu, Y. Park, P. H. Lee, Org. Lett., 2014, 16, 1144-1147.
The use of Zn powder in the presence of LiCl in THF allows a simple, high-yielding preparation of a broad range of functionalized aryl- and heteroarylzinc reagents. The synthesis of alkylzinc reagents was performed from inexpensive alkyl bromides.
A. Krasovski, V. Malakhov, A. Gavryushin, P. Knochel, Angew. Chem. Int. Ed., 2006, 45, 6040-6044.
Chemoselective cross-coupling of aliphatic and aromatic acyl chlorides with organostannanes provides a useful alternative to Friedel-Crafts acylations for the synthesis of ketones. A range of ketones are obtained in high yield using 2.5 mol % of bis(di-tert-butylchlorophosphine)palladium(II) dichloride as precatalyst. The catalyst tolerates various functional groups including aryl chlorides and bromides that usually undergo oxidative addition to palladium complexes.
R. Lerebours, A. Camacho-Soto, C. Wolf, J. Org. Chem., 2005, 70, 8601-8604.
The palladium-catalyzed coupling of 2-pyridyl esters with organoboron compounds is compatible with various functional groups and proceeds under mild reaction conditions. The coordination of the nitrogen atom to Pd is a key step for an efficient reaction.
H. Tatamidani, F. Kakiuchi, N. Chatani, Org. Lett., 2004, 6, 3597-3599.
An addition of arylboronic acids to nitriles catalyzed by a bipyridine-cyclopalladated ferrocenylimine complex can be conducted in aqueous media under acidic or basic conditions. The addition of NH4Cl has a drastic effect on the reaction yields.
A. Yu, J. Li, M. Cui, Y. Wu, Synlett, 2007, 3063-3067.
A mild and general protocol for the carbonylative Suzuki-Miyaura cross-coupling of sterically hindered ortho-disubstituted aryl iodides with various aryl boronic acids provides an array of substituted biaryl ketones in good yield. A carbonylative Negishi coupling that utilizes alkynyl nucleophiles is also described.
B. M. O'Keefe, N. Simmons, S. F. Martin, Org. Lett., 2008, 10, 5301-5304.
Tetraorganoindates, which are easily prepared from 1 eq. of InCl3 and 4 eq. of organometallics, could be employed as effective nucleophilic cross-coupling partners in Pd-catalyzed carbonylative cross-coupling reactions with a variety of halides. The present method gave unsymmetrical ketones in good yields.
S. W. Lee, K. Lee, D. Seomoon, S. Kim, H. Kim, H. Kim, E. Shim, M. Lee, J. Org. Chem., 2004, 69, 4852-4855.
A highly efficient heterogeneous palladium-catalyzed carbonylative cross-coupling of aryl iodides with triarylbismuths proceeds smoothly at atmospheric CO pressure and provides various valuable biaryl ketones with high atom economy, good to excellent yield, and recyclability of the catalyst.
W. Hao, H. Liu, L. Yin, M. Cai, J. Org. Chem., 2016, 81, 4244-4251.
N-Thiohydroxy succinimide esters (NTSEs) are versatile reagents, serving as both acyl and acylthio surrogates for the diverse synthesis of ketones, thioesters, amides, and acyl disulfides by selective cleavage of similarly reactive C-S and N-S bonds.
Y.-F. Li, Y.-F. Wei, J. Tian, J. Zhang, H.-H. Chang, W.-C. Gao, Org. Lett., 2022, 24, 5736-5740.
A copper-catalyzed oxidative cleavage reaction of terminal and internal alkynes using NFSI and TBHP provides aryl ketone products in good yields. NFSI not only functioned as N-centered radical precursor but also engaged in the aryl group migration. Mechanistic studies also suggested the important role of water.
L. Tang, F. Yang, H. Cheng, C. Tan, C. Jin, H. Chen, Y. Huang, S. Zhang, S. Zhang, W. Song, J. Tan, Org. Lett., 2020, 22, 8618-8623.
meso-2,4-Bis(diphenylphosphino)pentane (mBDPP) is an effective regiocontrolling ligand for palladium-catalyzed internal arylation of electron-rich olefins in DMSO with no need for any halide scavengers.
S. Liu, N. Berry, N. Thomson, A. Pettman, Z. Hyder, J. Mo, J. Xiao, J. Org. Chem., 2006, 71, 7467-7470.
Ammonium salts that can act as hydrogen-bond donors exert a remarkable acceleration on the rates of the regioselective arylation of electron-rich olefins by aryl halides in ionic liquids and common solvents.
J. Mo, J. Xiao, Angew. Chem. Int. Ed., 2006, 45, 4152-4157.
Palladium-catalyzed regioselective Heck arylation of various electron-rich olefins has been accomplished in imidazolium ionic liquids with a wide range of aryl bromides and iodides. The reaction proceeded with high efficiency and remarkable regioselectivity. The chemistry provides a simple, effective method for preparing branched olefins and contributes to the extension of the Heck reaction to a wider range of substrates.
J. Mo, L. Xu, J. Xiao, J. Am. Chem. Soc., 2005, 127, 751-760.
A mild and efficient protocol for palladium-catalyzed oxidative Heck reactions of arylboronic acids with both electron-rich and -deficient olefins works in the absence of a base, oxygen, or other external oxidants. With a wide variety of substrates tolerated, the method broadens the scope of palladium-catalyzed coupling reactions.
J. Ruan, X. Li, O. Saidi, J. Xiao, J. Am. Chem. Soc., 2008, 130, 2424-2425.
A copper-catalyzed aerobic C-C cleavage of single bonds enables a transformation of epoxides into ketones.
L. Gu, C. Jin, H. Zhang, L. Zhang, J. Org. Chem., 2014, 79, 8453-8456.
A Pd(II)-catalyzed denitrogenative and desulfinative addition of arylsulfonyl hydrazides to nitriles provides aryl ketones under mild conditions. The reaction tolerates many common functional groups, and works well in the presence of electron-donating and electron-withdrawing substituents.
M. Meng, L. Yang, K. Cheng, C. Qi, J. Org. Chem., 2018, 83, 3275-3284.
A selective acylation of readily accessible organomagnesium reagents with commercially available esters proceeds in short residence times in continuous flow. Flow conditions prevent premature collapse of the hemiacetal intermediates despite noncryogenic conditions, thus furnishing ketones in good yields.
B. Heinz, D. Djukanovic, M. A. Ganiek, B. Martin, B. Schenkel, P. Knochel, Org. Lett., 2020, 22, 493-496.
In a highly regio- and stereoselective hydroarylation, hydroalkenylation, and hydrobenzylation of ynol ethers, a Pd-catalyzed reductive addition of organohalides, including aryl, alkenyl, and benzyl halides, in the presence of 2-propanol gives α,β- and β,β-disubstituted olefinic ethers in good yields.
W. Cui, J. Yin, R. Zheng, C. Cheng, Y. Bai, G. Zhu, J. Org. Chem., 2014, 79, 3487-3493.
In a general method for the preparation of α-hydroxyacetophenones, functionalized arylmagnesium species are transmetalated to the corresponding arylzinc intermediates, which undergo Cu(I)-catalyzed reaction with acetoxyacetyl chloride. Acidic hydrolysis of the acetate group releases the target α-hydroxyacetophenones with minimal production of undesired polymeric side products.
M. McLaughlin, J. M. Belyk, G. Qian, R. A .Reamer, C.-y. Chen, J. Org. Chem., 2012, 77, 5144-5148.
A palladium catalyzed carbonylation of aryl iodides using near stoichiometric amounts of carbon monoxide enables the synthesis of monoprotected 1,3-ketoaldehydes. Besides representing platforms for a variety of heterocyclic structures, these motives serve as viable precursors for the highly relevant aryl methyl ketones.
T. M. Gøgsig, D. U. Nielsen, A. T. Lindhardt, T. Skrydstrup, Org. Lett., 2012, 14, 2536-2539.
Silylated cyanohydrins of iodo-substituted aryl, heteroaryl, or cycloalkenyl ketones undergo an I/Mg-exchange using i-PrMgCl·LiCl. After subsequent reactions with electrophiles, a facile deprotection produces polyfunctional ketones in good overall yiels. An extension to aromatic iodoaldehydes is described.
C.-Y. Liu, H. Ren, P. Knochel, Org. Lett., 2006, 8, 617-629.
Highly regioselective and efficient Heck reactions of aryl triflates with N-acyl-N-vinylamines were achieved using Pd2(dba)3, dppf, and diethylisopropylamine in dioxane. The coupling products easily underwent acidic hydrolysis to the corresponding aryl methyl ketones or in situ hydrogenation in the presence of (Ph3P)3RhCl under a hydrogen atmosphere to provide the N-acyl derivatives of benzylic amines.
A. L. Hansen, T. Skydstrup, J. Org. Chem., 2005, 70, 5997-6003.
A new method for the synthesis of organoborates starting from α,β-unsaturated acetals was developed. The available alkoxy-functionalized butadienyl- and styrylboronic esters cross couple effectively with a broad spectrum of aryl halides under mild conditions. The new methods also provide an effective approach to aromatic ketones.
P. B. Tivola, A. Deagostino, C. Prandi, P. Venturello, Org. Lett., 2002, 4, 1275-1277.
1-Siloxy-1-alkenylcopper species were generated by 1,2-Csp2-to-O silyl migration of the copper enolates of acyltriphenylsilanes. The alkenylcopper species reacted with methyl, benzyl, allylic, tributylstannyl halides and in the presence of Pd(0) catalyst with aryl and alkenyl iodides to give geometrically pure (Z)-enol silyl ethers.
A. Tsubouchi, K. Onishi, T. Takeda, J. Am. Chem. Soc., 2006, 128, 14268-14269.
The first enantioselective desymmetrizations of anhydrides with carbon-based nucleophiles nucleophiles by employing (-)-sparteine as a chiral ligand are described. These C-C bond-forming reactions proceed in good enantioselectivity for a range of anhydrides.
R. Shintani, G. C. Fu, Angew. Chem. Int. Ed., 2002, 41, 1057-1059.
The use of titanium(IV) chloride as a Lewis acid for direct ortho-acylation of phenols and naphthols proves to be a convenient, more general and direct route to various hydroxyaryl ketones. The route is regioselective, leading to ortho C-acylated products in satisfactory to high yields in most cases.
A. Bensari, N. T. Zaveri, Synthesis, 2003, 267-271.
tert-Butyl isocyanide insertion enables a simple and efficient palladium-catalyzed carbonylative Sonogashira coupling. This methodology demonstrates the utility of isocyanides in intermolecular C-C bond construction and provides a novel pathway for the synthesis of alkynyl imines which can undergo simple silica gel catalyzed hydrolysis to afford alkynones. The approach is tolerant of a wide range of substrates and applicable to library synthesis.
T. Tang, X.-D. Fei, Z.-Y. Ge, Z. Chen, Y.-M. Zhu, S.-J. Ji, J. Org. Chem., 2013, 78, 3170-3175.
A palladium-catalyzed carbonylative Sonogashira coupling of aryl bromides using near stoichiometric amounts of carbon monoxide converts a broad substrate scope in good yields. The formed alkynone motive serves as a platform for the synthesis of various heterocyclic structures, including pyrimidines. Furthermore, the presented strategy allows effective 13C labeling.
K. T. Neumann, S. R. Laursen, A. T. Lindhardt, B. Bang-Andersen, T. Skrydstrup, Org. Lett., 2014, 16, 2216-2219.
A Pd-catalyzed copper-free carbonylative Sonogashira coupling reaction at room temperature was achieved by using water as a solvent under balloon pressure of CO with Et3N as a base.
B. Liang, M. Huang, Z. You, Z. Xiong, K. Lu, R. Fathi, J. Chen, Z. Yang, J. Org. Chem., 2005, 70, 6097-6100.
Carbonylative coupling of terminal alkynes with aryliodides in the presence of PdCl2(PPh3)2 as catalyst in 2 eq. of 0.5 M aqueous ammonia, and CO (1 atm) gives the corresponding α,β-alkynyl ketones in good yields.
M. S. M. Ahmed, A. Mori, Org. Lett., 2003, 5, 3057-3060.
Starting from readily available aryl iodides and allenes, with formic acid as the CO source and reductant, good yields of α-branched enones were isolated. The use of a CO source avoids the manipulation of CO gas.
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A practical, convenient, and highly selective Pd-catalyzed addition of organoboron reagents to dinitriles provides β-ketonitriles with excellent functional-group tolerance and a broad scope of substrates.
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3-Oxo-3-(hetero)arylpropanenitriles can be synthesized via a carbonylative palladium-catalyzed α-arylation of tert-butyl 2-cyanoacetates with (hetero)aryl bromides followed by an acid-mediated decarboxylation step. Through the combination of only a stoichiometric loading of carbon monoxide and mild basic reaction conditions for the deprotonation step, an excellent functional group tolerance was ensured.
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Acyl substitution of readily accessible α-siloxy Weinreb amides with organolithium compounds provides diverse cross-benzoin and α-siloxy ketone products. Enantiopure benzoins can be accessed via a chiral pool approach.
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A concerted metallophotoredox catalysis enables an efficient decarboxylative functionalization of α,β-unsaturated carboxylic acids with aryl iodides in the presence of perylene bisimide dye to afford 1,2-diketones.
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A convenient Pd-catalyzed reaction of aryl halides, tert-butyl isocyanide as the CO source, and organoaluminum reagents provides 1,2-diketones in very good yields and with good functional group tolerance.
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Benzil derivatives such as diaryl 1,2-diketones are synthesized via a direct copper-catalyzed decarboxylative coupling reaction of aryl propiolic acids with aryl iodides followed by an oxidation. The reaction shows good functional group tolerance toward ester, aldehyde, cyano, and nitro groups. In addition, symmetrical diaryl 1,2-diketones are obtained from aryl iodides and propiolic acid in the presence of palladium and copper catalysts.
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A general Pd-catalyzed double carbonylation of aryl iodides with secondary or primary amines provides α-ketoamides in high yields with excellent chemoselectivities at atmospheric CO pressure. This transformation proceeds successfully even at room temperature and in the absence of any ligand and additive.
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A tandem metal-free oxidative aryl migration/C-C bond-cleavage reaction, mediated by hypervalent iodine reagent, provides straightforward access to important α-ketoamide and α-ketoester derivatives from readily available acrylic derivatives via a concerted process of 1,2-aryl shift concomitant with C-C bond cleavage.
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The Pd-catalyzed reaction between aryl or vinyl iodides and ethyl diazoacetate (EDA) provides cross-coupling products in good yields.
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A Regel-type transition-metal-free direct C-2 aroylation of (benzo)oxazoles, (benzo)thiazoles and 1,3,4-oxadiazoles with acid chlorides is catalyzed by N,N-dimethyl-4-aminopyridine (DMAP) and affords the corresponding 2-ketoazoles in good yields.
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