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 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 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.
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.
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.
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.
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.
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 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.
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.
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.
M. T. Jensen, M. Juhl, D. U. Nielsen, M. F. Jacobsen, A. T. Lindhardt, T. Skrydstrup, J. Org. Chem., 2016, 81, 1358-1366.
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.
H. Min, T. Palani, K. Park, J. Hwang, S. Lee, J. Org. Chem., 2014, 79, 6279-6285.
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.
H. Du, Q. Ruan, M. Qi, W. Han, J. Org. Chem., 2015, 80, 7816-7823.
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.
L. Liu, L. Du, D. Zhang-Negrerie, Y. Du, K. Zhao, Org. Lett., 2014, 16, 5772-5775.
The Pd-catalyzed reaction between aryl or vinyl iodides and ethyl diazoacetate (EDA) provides cross-coupling products in good yields.
C. Peng, J. Cheng, J. Wang, J. Am. Chem. Soc., 2007, 129, 8708-8709.
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.
P. Lassalas, F. Marsais, C. Hoarau, Synlett, 2013, 24, 2233-2240.
A palladium-catalyzed intramolecular carbonylative annulation with phenyl formate as a CO source enables an efficient synthesis of 2-substituted indene-1,3(2H)-diones from stable and readily available 1-(2-halophenyl)-1,3-diones using K3PO4 as a base and DMSO as a solvent at 95 °C. The reaction offers a broad substrate scope with good to excellent yields.
Y. Zhang, J.-L. Chen, Z.-B. Chen, Y.-M. Zhu, S.-J. Ji, J. Org. Chem., 2015, 80, 10643-10650.