Categories: C-C Bond Formation > Arenes >
α-Arylation
Recent Literature
Anilines and ethyl vinyl ether can be combined in a safe continuous-flow process to achieve efficient and mono-selective formal α-arylation of acetaldehyde.
The mild non-basic reaction conditions of this method allow for high functional group tolerance. This process also provides means
for a safe and scalable generation of aryldiazonium salts and enables preparation of an array of synthetically valuable monoarylated acetaldehydes.
N. Chernyak, S. L. Buchwald, J. Am. Chem. Soc., 2012,
134, 12466-12469.
2-Methyl-2'-dicyclohexylphosphinobiphenyl is a particularly effective ligand
for the Pd-catalyzed α-arylation. With 0.1-1.0 mol% Pd, a large variety of aryl
halides and ketones react efficiently and with high selectivity. For two types
of substrates, BINAP and Xantphos are more effective than biphenyl-based ligands.
K3PO4 can also be used as the base in the presence of
base-sensitive functional groups.
J. M. Fox, X. Huang, A. Chieffi, S. L. Buchwald, J. Am. Chem. Soc., 2000,
122, 1360-1370.
The rational design of a phosphine ligand for the Pd-catalyzed mono-α-arylation
of acetone enables the conversion of a broad range of aryl chlorides and
provides excellent product yields with down to 0.1 mol % Pd. Preliminary
investigations suggest that the rate-limiting step for the proposed system is
the oxidative addition of aryl chlorides.
W. C. Fu, C. M. So, W. K. Chow, O. Y. Yuen, F. Y. Kwong, Org. Lett.,
2015,
17, 4612-4615.
The use of appropriately designed P,N-ligands proved to be the key to
controlling the reactivity and selectivity in Pd-catalyzed mono-α-arylation of
acetone with aryl chlorides, bromides, iodides, and tosylates. The reaction
affords good yields with substrates containing a range of functional groups at
modest Pd loadings using Cs2CO3 as the base and employing
acetone as both a reagent and the solvent.
K. D. Hesp, R. J. Lundgren, M. Stradiotto, J. Am. Chem. Soc., 2011,
133, 5194-5197.
A traceless protecting strategy enables a palladium-catalyzed α-arylation of
carboxylic aids and secondary amides with aryl halides. Both coupling processes
occur with various carboxylic acids and amides and with a variety of aryl
bromides containing a broad range of functional groups, including base-sensitive
functionality like acyl, alkoxycarbonyl, nitro, cyano, and even hydroxyl groups.
Z.-T. He, J. F. Hartwig, J. Am. Chem. Soc.,
2019,
141, 11749-11753.
A high-efficiency and practical Cu-catalyzed cross-coupling of readily
available aryl bromides (or chlorides) with malonates provides versatile
α-aryl-esters. The reactions are smoothly conducted in the presence of a low
CuCl loading, an oxalamide ligand, and a green solvent. A variety of
functional groups are tolerated.
F. Cheng, T. Chen, Y.-Q. Huang, J.-W. Li, C. Zhou, X. Xiao, F.-E. Chen, Org. Lett.,
2022, 24, 115-120.
The merger of aerobic oxidative Cu catalysis with decarboxylative enolate
interception enables a decarboxylative carbonyl α-arylation of arylboron
nucleophiles with malonic acid derivatives. This method converts substrates
containing electrophilic functional groups that are incompatible with existing
α-arylation methods.
P. J. Moon, S. Yin, R. J. Lundgren, J. Am. Chem. Soc., 2016,
138, 13826-13829.
A palladium-catalyzed coupling of aryl halides and ester enolates produced
α-aryl esters in high yields at room temperature. The reaction was highly
tolerant of functionalities and substitution patterns on the aryl halide.
Improved protocols for the selective monoarylation of tert-butyl
acetate and the efficient arylation of α,α-disubstituted esters were
developed with LiNCy2 as base and P(t-Bu)3 as ligand.
M. Jørgensen, S. Lee, X. Liu, J. P. Wolkowski, J. F. Hartwig, J. Am. Chem. Soc., 2002,
124, 12557-12565.
Palladium-catalyzed α-arylations of chloroarenes with the sodium enolates of
tert-butyl propionate and methyl isobutyrate occur in high yields using P(t-Bu)3
as ligand. The reactions of chloroarenes with the Reformatsky reagent of tert-butyl
acetate were most challenging but occurred in high yields for chlorobenzene and
electron-poor chloroarenes.
T. Hama, J. F. Hartwig, Org. Lett., 2008,
10, 1549-1552.
A catalyst system, consisting of [Pd(2-butenyl)Cl]2 and MorDalPhos,
exhibited high catalytic reactivity toward a mono-α-arylation of aryl and
heteroaryl ketones with aryl phosphates. A wide range of aryl phosphates were
efficiently coupled with aryl and heteroaryl ketones with good selectivity and
very good yields.
X. Chen, Z. Chen, C. M. So, J. Org. Chem., 2019, 84,
6337-6346.
An easily available NHC-Pd(II)-Im complex is an efficient catalyst for the
α-arylation reaction between ketones and aryl chlorides. Under the optimal
conditions, all reactions proceeded smoothly to give the desired products in
very good yields within hours.
Z.-K. Xiao, L.-X. Shao, Synthesis, 2012, 44,
711-716.
Enhanced steric congestion of an indolyl-derived phosphine ligand enables a
Pd-catalyzed mono-α-arylation of aryl- and heteroarylketones with aryl mesylates
and tosylates. This protocol is suitable for modifications of biological
phenolic compounds, rendering it amenable for functionalization of phenolic (pro)drugs.
W. C. Fu, C. M. So, O. Y. Yuen, I. T. C. Lee, F. Y. Kwong, Org. Lett., 2016, 18,
1872-1875.
A cobalt-catalyzed enantioconvergent cross-coupling of α-bromoketones with
aryl zinc reagents provides chiral ketones bearing α-tertiary stereogenic
centers with high enantioselectivities. Adjusting the electronic effect of
chiral unsymmetric N,N,N-tridentate ligands is critical for improving the
reactivity and selectivity of this transformation.
J. Wang, X. Shen, X. Chen, Y. Bao, J. He, Z. Lu, J. Am. Chem. Soc.,
2023, 145, 24958-24964.
A simple one-pot procedure for the palladium-catalyzed intermolecular
α-arylation of esters with a wide range of aryl bromides using Pd(OAc)2 or
Pd2(dba)3, bulky electron-rich o-biphenyl phosphines and LiHMDS as a base
provides monoarylated products at room temperature or at 80 °C with very good
yields. A catalyst system for the α-arylation of esters using aryl chlorides is
also described.
W. A. Moradi, S. L. Buchwald, J. Am. Chem. Soc., 2001,
123, 7996-8002.
An efficient monoarylation of acetate esters and aryl
methyl ketones with aryl chlorides is easily accomplished under mild conditions,
that tolerate a wide array of heterocyclic substrates, using recently reported palladium precatalysts.
M. R. Biscoe, S. L. Buchwald, Org. Lett., 2009,
11, 1773-1775.
M. R. Biscoe, S. L. Buchwald, Org. Lett., 2009,
11, 1773-1775.
The complex (IPr)Pd(acac)Cl has proven to be a highly active PdII
precatalyst in Buchwald-Hartwig reactions and α-ketone arylations of a wide
range of substrates including unactivated, sterically
hindered, and heterocyclic aryl chlorides.
N. Marion, E. C. Ecarnot, O. Navarro, D. Amoroso, A. Bell, S. P. Nolan, J. Org. Chem., 2006,
71, 3816-3821.
β-Diketones can undergo a reaction with aryl halides in the presence of Cu(I) or
Cu(II) salts in DMSO using K3PO4 • 3 H2O
without ligands to form various α-aryl ketones. H2O assists the C-C
activation. This simple, practical method complements classic methods for the
rapid construction of C-C bonds to a carbonyl moiety.
C. He, S. Guo, L. Huang, A. Lei, J. Am. Chem. Soc., 2010,
132, 8273-8275.
The use of gem-bis(boronates) as precursors enables a construction of
quaternary α-aryl aldehydes, in which both groups are installed simultaneously.
This methodology provides a general strategy to produce quaternary α-aryl
aldehydes with broad scopes and synthetic convenience. In addition, gem-bis(boronates)
are readily available from ketones.
P. Zheng, Y. Zhai, X. Zhao, T. Xu, Org. Lett.,
2019, 21, 393-396.
An improved protocol for the Pd-catalyzed α-arylation of aldehydes with aryl
halides allows the coupling of
an array of substrates including challenging electron-rich aryl bromides and
less reactive aryl chlorides. The utility of this method has been demonstrated
in a total synthesis of (±)-sporochnol.
R. Martín, S. L. Buchwald, Org. Lett.,
2008,
10, 4561-4564.
A palladium-catalyzed α-arylation of ketones with readily available
nitroarenes and nitroheteroarenes provides α-aryl and α-heteroaryl ketones. The
use of BrettPhos as ligand was crucial for high efficiency.
Z. Li, Y. Peng, T. Wu, A. Das, Org. Lett., 2021, 23,
881-885.
A Rh(I)-catalyzed cross-coupling of diazoesters with arylsiloxanes enables the
synthesis of α-aryl esters via Rh(I)-carbene migratory insertion. The reaction
represents the first example of utilizing arylsiloxane as the coupling partner
in a carbene-involved cross-coupling reaction.
Y. Xia, Z. Liu, S. Feng, F. Ye, Y. Zhang, J. Wang, Org. Lett.,
2015,
17, 956-959.
A general, chemoselective, and efficient synthesis of diarylacetate was
accomplished through rhodium catalyzed direct arylation of diazo compounds with
arylboronic acids. The reaction tolerates various boronic acid derivatives and
functional groups.
J. Ghorai, P. Anbarasan, J. Org. Chem.,
2015,
80, 3455-3461.
An enantioselective α-arylation of aldehydes has been accomplished using
diaryliodonium salts and a combination of copper and organic catalysts. These
mild catalytic conditions allow the enantioselective construction and retention
of enolizable α-formyl benzylic stereocenters, a valuable synthon for the
production of medicinal agents.
A. E. Allen, D. W. C. MacMillan, J. Am. Chem. Soc., 2011,
133, 4260-4263.
A catalytic asymmetric cross-coupling of α-halo carbonyl compounds with aryl
metal reagents generates synthetically useful α-aryl carboxylic acid derivatives
in good enantiomeric excess. The method can also be applied to enantioselective
alkenylation reactions.
X. Dai, N. A. Strotman, G. C. Fu, J. Am. Chem. Soc., 2008,
130, 3302-3303.
A Suzuki-Miyaura cross-coupling of α-pyridinium esters and arylboroxines
provides α-aryl esters and amides. Combined with formation of the pyridinium
salts, this method enables an efficient transformation of amino acid derivatives
under mild conditions and broad functional group tolerance.
M. E. Hoerrner, K. M. Baker, C. H. Basch, E. M. Bampo, M. P. Watson,
Org. Lett., 2019, 21, 7356-7360.
A palladium-catalyzed deprotonative cross-coupling process (DCCP) enables a
γ-arylation of aryl acetic acids with wide range of aryl bromides and chlorides.
A procedure for the palladium-catalyzed α-arylation of styryl acetic acids is
also described.
S.-C. Sha, J. Zhang, P. J. Walsh, Org. Lett.,
2015,
17, 410-413.
In a simple protocol for the synthesis of α-diarylacetic esters from benzoins,
in situ generated acetals assist rapid 1,2-aryl migration in a stereospecific
manner, paving the way to make enantioenriched α-diarylacetic esters from easily
accessible enantiopure benzoins.
R. B. Kothapalli, R. Niddana, R. Balmurugan, Org. Lett., 2014,
16, 1278-1281.
An iron-catalyzed oxidative dehydrogenation enables an α-arylation of
deoxybenzoins with non-prefunctionalized arenes with broad substrate scope and
functional group tolerance. The reaction provides efficient access to
synthetically useful 1,2,2-triarylethanones.
T. Chen, Y.-F. Li, Y. An, F.-M. Zhang, Org. Lett.,
2016, 18, 4754-4757.
2-aryl-1,3-dicarbonyl compounds are produced in good yields by a CuI/L-proline-catalyzed
arylation of activated methylene compounds with aryl iodides and aryl
bromides in DMSO at 40-50°C in the presence of Cs2CO3.
X. Xie, G. Cai, D. Ma, Org. Lett.,
2005,
7, 4693-4695.
In situ generated hypoiodite catalyzes an oxidative rearrangement of
chalcones under mild and metal-free conditions. This environmental-benign
protocol avoids the use of rare or toxic metals.
M. Zheng, C. Huang, J.-Z. Yan, S.-L. Xie, S.-J. Ke, H.-D. Xia, Y.-N. Duan, J. Org. Chem., 2023, 88,
1504-1514.
In a Pd-catalyzed formation of arylnitromethanes from readily available aryl
halides or triflates, 2-10 equiv of nitromethane in dioxane as solvent can be
employed in comparison to prior work that used nitromethane as solvent (185
equiv). The present transformation reduces the hazards associated with MeNO2,
provides high yields at relatively low temperatures, and tolerates an array of
functionality.
R. R. Walvoord, M. C. Kozlowski, J. Org. Chem., 2013,
78, 8859-8864.
An efficient cross-coupling reaction of aryl halides and nitromethane gives
arylnitromethane products, that are precursors for numerous useful synthetic
products. An efficient method for their direct conversion to the corresponding
oximes and aldehydes in a one-pot operation has been discovered. The process
exploits inexpensive nitromethane as a carbonyl equivalent, providing a mild and
convenient formylation method.
R. R. Walvoord, S. Berritt, M. C. Kozlowski, Org. Lett., 2012,
14, 4086-4089.
An efficient, mild, and metal-free arylation of nitroalkanes with diaryliodonium
salts has gives convenient access to tertiary nitro compounds in high yields
without the need for excess reagents. The C-arylation can be extended to
α-arylation of nitroesters and tolerates other easily arylated functional groups,
such as phenols and aliphatic alcohols.
C. Dey, E. Lindstedt, B. Olofsson, Org. Lett.,
2015,
17, 4554-4557.
A general method for the Suzuki-Miyaura and
carbonyl enolate coupling of unactivated arenesulfonates was developed
utilizing Pd(OAc)2 and XPhos as ligand. The catalyst system effects
the coupling of various aryl, heteroaryl, and extremely hindered arylboronic acids
and carbonyl enolates with
different aryl tosylates, under mild conditions.
H. N. Nguyen, X. Huang, S. L. Buchwald, J. Am. Chem. Soc., 2003,
125, 11818-11819.
The reaction between aryl- or vinylboroxines with
α-diazocarbonyl compounds offers an alternative approach for α-arylation and α-vinylation of carbonyl
compounds. α-Arylated or α-vinylated
carbonyl compounds are formed under mild conditions.
C. Peng, W. Zhang, G. Yan, J. Wang, Org. Lett., 2009,
11, 1667-1670.
Reaction of β-bromo alcohols with 0.6 equiv of Et2Zn forms a zinc
complex in CH2Cl2 at room temperature, followed by
1,2-migration to give the corresponding carbonyl compounds. This mild and clean
rearrangement is general for acyclic and cyclic bromohydrins, and a variety of
ring-expansive and -contractive carbonyl compounds were obtained in very good
yields.
L. Li, P. Cai, Q. Guo, S. Xue, J. Org. Chem., 2008,
73, 3452-3459.
An efficient Pd-catalyzed direct intermolecular α-arylation of acetamide
derivatives with aryl chlorides offers chemoselectivities up to 10:1 in mono-
and diarylation by careful selection of bases, solvents, and stoichiometry.
Bis-arylated amides can be prepared in up to 95% yield.
B. Zheng, T. Jia, P. Walsh, Org. Lett., 2013,
15, 4150-4153.
The use of zinc enolates (isolated Reformatsky reagents or generated in situ
from α-bromo amides or lithium enolates) instead of alkali metal enolates,
greatly expands the scope of the palladium-catalyzed α-arylation of aryl
bromides and vinyl bromides.
T. Hama, D. A. Culkin, J. F. Hartwig, J. Am. Chem. Soc.,
2006,
128, 4976-4985.
Aryl radicals generated in situ from arene diazonium fluoroborates promoted by
ascorbic acid enable a convenient and general oxidative arylation of vinyl
arenes in air at room temperature in the absence of any additive and visible
light irradiation. Various 2-aryl acetophenones have been obtained in good
yields.
B. Majhi, D. Kundu, B. C. Ranu, J. Org. Chem.,
2015,
80, 7739-7745.
The copper-catalyzed highly regioselective reaction of aryl alkyl alkynes and
arylpropargylic alcohols with diaryliodonium salts gives α-arylketones in good
yields under mild conditions. Depending on the internal alkyne substrate,
two different arylation-oxygenation pathways under different reaction conditions
have been elaborated based on deuterated experiments, controlling experiments,
and spectroscopic analysis of reaction intermediates.
Z.-F. Xu, C.-X. Cai, J.-T. Liu, Org. Lett., 2013,
15, 2096-2099.
A protocol for Pd(II)-catalyzed asymmetric arylation of N-aryl imino
esters affords a practical and direct access to chiral arylglycine derivatives
in good yields and with high enantioselectivities.
J. Chen, X. Lu, W. Lou, Y. Ye, H. Jiang, W. Zeng, J. Org. Chem., 2012,
77, 8541-8548.
The coupling of aryl iodides and diethyl malonate in the presence of Cs2CO3 and catalytic amounts of CuI and 2-phenylphenol gave α-aryl malonates in good to excellent yields. This mild method tolerates various functional groups.
E. J. Hennessy, S. L. Buchwald, Org. Lett., 2002, 4, 269-272.
β-Ketoesters can directly be transformed to the corresponding α-hydroxymalonic
esters, tartronic esters, with molecular oxygen catalyzed by calcium iodide
under visible light irradiation from a fluorescent lamp. This convenient tandem
oxidation/rearrangement reduces consumption of energy, time, and solvents.
N. Kanai, H. Nakayama, N. Tada, A. Itoh, Org. Lett., 2010,
12, 1948-1951.
A one-pot procedure for the synthesis of 2-alkyl-2-arylcyanoacetates based on a
Pd(OAc)2/dppf-catalyzed enolate arylation followed by in situ
alkylation tolerates a diverse range of aryl and heteroaryl bromides, and
provides a rapid entry to a wide range of products in very good to yield.
X. Wang, A. Guram, E. Bunel, G.-Q. Cao, J. R. Allen, M. M. Faul, J. Org. Chem., 2008,
73, 1643-1645.
The use of tBuXPhos as ligand enabled palladium-catalyzed cross-coupling
of aryl bromides with very acidic nitroacetates to afford
2-aryl-2-nitroacetates.
A. E. Metz, S. Berritt, S. D. Dreher, M. C. Kozlowski, Org. Lett., 2012,
14, 760-763.
α-Aryl cyanoacetates are useful intermediates in the preparation of amino
alcohols, β-amino acids, and arylacetic acids. The discovery and
optimization of a new method for bond construction using high-throughput
screening provided a mild arylation of cyanoesters with broad reaction scope
and the ability to construct materials with highly hindered quaternary carbons.
S. R. Stauffer, N. A. Beare, J. P. Stambuli, J. F. Hartwig, J. Am. Chem. Soc., 2001,
123, 4641-4642.
A Pd-catalyzed α-arylation of esters and protected amino acids provides a
short, general route to α-aryl carboxylic acids and α-aryl amino acids in good
yields. Glycinates are activated for direct coupling by unsaturated amine
protecting groups.
S. Lee, N. A. Beare, J. F. Hartwig, J. Am. Chem. Soc., 2001,
123, 8410-8411.
A direct α-arylation of secondary β-keto amides with arynes, generated by
fluoride-induced elimination of ortho-silyl aryltriflates, proceeds via
an interrupted insertion reaction of arynes and leads to densely functionalized
aromatic compounds exhibiting a chiral ‘all carbon’ quaternary center under
transition-metal-free conditions. An organocatalytic asymmetric version of the
reaction also proved possible.
K. Mohanan, Y. Coquerel, J. Rodriguez, Org. Lett., 2012,
14, 4686-4689.
A catalyst system derived from commercially available Pd2(dba)3
and PtBu3 enables the coupling of α-keto ester enolates and
aryl bromides to provide an array of β-stereogenic α-keto esters. The derived
products are of broad interest given the prevalence of the α-keto acid
substructure in biologically important molecules.
B. P. Zavesky, S. L. Bartlett, J. S. Johnson, Org. Lett.,
2017, 19, 2126-2129.
A protected pyruvate equivalent allows arylation and arylation/alkylation
reactions to be performed at the methyl group. For example, palladium catalyzed
arylation reactions of the OBO derivative of the pyruvate ester can be followed
by alkylation under basic conditions. Moreover, the OBO protecting group could
be easily removed in one step to provide access to a wide range of substituted
pyruvate derivatives.
C. H. A. Esteves, C. J. J. Hall, P. D. Smith, T. J. Donohoe, Org. Lett.,
2017, 19, 5248-5251.
A one-pot protocol for the cyanomethylation of aryl halides through a
palladium-catalyzed reaction with isoxazole-4-boronic acid pinacol ester
proceeds through Suzuki coupling, base-induced fragmentation, and deformylation.
Under optimized conditions (PdCl2dppf, KF, DMSO/H2O, 130
°C) a broad spectrum of aryl bromides could be converted into arylacetonitriles
in good yields.
J. Velcicky, A. Soicke, R. Steiner, H.-G. Schmalz, J. Am. Chem. Soc., 2011,
133, 6948-6951.
A general method for the direct α-arylation of nitriles with aryl chlorides
was developed. With a catalytic system generated from palladium and a commercially available
ligand, it is now possible to effect direct α-arylation using a wide variety of
starting materials.
J. You, J. G. Verkade, Angew. Chem., 2003,
115, 5205-5207.
TMPZnCl·LiCl as a kinetically highly active base enables a Pd-catalyzed
α-arylation of nitriles and esters under mild conditions. Remarkably, even a
regioselective γ-arylation or a γ-alkenylation of α,β- or β,γ-unsaturated
nitriles can be observed.
S. Duez, S. Bernhardt, J. Heppekausen, F. F. Fleming, P. Knochel, Org. Lett., 2011,
13, 1690-1693.
A palladium-catalyzed α-arylation of nitriles was developed by exploring the structure and reactivity of arylpalladium cyanoalkyl complexes. The high yields and short reaction times observed for BINAP-ligated complexes suggested that BINAP-ligated palladium catalysts might be appropriate for the arylation of nitriles. Initial results on a palladium-catalyzed process for the direct coupling of aryl bromides and primary, benzylic, and secondary nitrile anions to form α-aryl nitriles in good yields are reported.
D. A. Culkin, J. F. Hartwig, J. Am. Chem. Soc., 2002,
124, 9330-9331.
α-Cyanohydrin triflates undergo Pd-catalyzed cross-coupling with aryl and vinyl
boronic acids under mild conditions. Coupling proceeds with complete inversion
of configuration at the stereogenic carbon. The resultant nitrile can be easily
converted into a variety of alternative functional groups of value in organic
synthesis and thus a high level of molecular diversity can be achieved.
A. He, J. R. Falck, J. Am. Chem. Soc., 2010,
132, 2524-2525.
Palladium-N-heterocyclic carbene (NHC) complexes were found to be
active catalysts for the arylation of various ketones with aryl chlorides,
bromides, and triflates in short reaction times.
M. S. Viciu, R. F. Germaneau, S. P. Nolan., Org.
Lett., 2002, 4, 4053-4056.
A convenient method has been developed for the palladium-catalyzed arylation of
malononitrile in high yields with aryl bromides and chlorides, respectively. The
influence of several reaction parameters such as base, ligand, solvent or
temperature were investigated.
A. Schnyder, A. F. Indolese, T. Maetzke, J. Wenger, H.-U. Blaser, Synlett, 2006,
3167-3168.
Potassium tert-butoxide promotes a direct arylation of
2-substituted malononitriles using diaryliodonium salts without transition-metal
catalysts. The desired 2-substituted α-arylmalononitriles derivatives were
synthesized in very good yields.
J. Han, X. Qian, B. Xu, L. Wang,
Synlett, 2017, 28, 2139-2142.
In a palladium catalyzed Negishi-type α-arylation of sulfones and sulfonamides
with a broad range of aryl bromides, the substrates are selectively metalated in
situ with tmp·ZnCl·LiCl base and cross-coupled in the presence of a catalyst
system that is generated from Pd(dba)2 and XPhos.
T. Knauber, J. Tucker, J. Org. Chem.,
2016,
81, 5636-5648.
Deprotonation of the weakly acidic α-protons of sulfoxides with LiOtBu and the
use of a palladium phosphine complex as catalyst facilitates an α-arylation of
various aryl methyl sulfoxides with aryl bromides. More challenging coupling
partners, such as alkyl methyl sulfoxides (including dimethyl sulfoxide) and
aryl chlorides proved to be suitable under optimized conditions.
T. Jia, A. Bellomo, K. El Baina, S. D. Dreher, P. J. Walsh, J. Am. Chem. Soc., 2013,
135, 3740-3743.
A nickel-catalyzed cross-electrophile coupling of aryl iodides with α-bromo
sulfoxide provides a diverse array of aryl benzyl sulfoxides under mild
conditions with excellent functional group tolerance. Optically enriched
sulfoxides could be coupled with aryl iodides to generate the corresponding
sulfoxides with excellent stereochemical integrity.
Q. Liu, T. Lin, Y.-e. Wang, W. Liang, L. Cao, X. Sheng, D. Xiong, J. Mao, Org. Lett., 2023, 25,
9153-9157.
A Pd(OAc)2/Xantphos-based catalyst enabled a deprotonative
cross-coupling process between benzyl diphenyl or dicyclohexyl phosphine oxide
derivatives and aryl bromides to prepare diarylmethyl phosphine oxides in very
good yields.
S. Montel, T. Jia, P. J. Walsh, Org. Lett., 2014,
16, 130-133.
A deprotonative cross-coupling process (DCCP) enables a new synthetic route to access diarylmethyl phosphonates
via introduction of aromatic groups on benzylic phosphonates. A catalytic system
based on Pd(OAc)2/CataCXium
A allows a reaction between benzyl diisopropyl phosphonate
derivatives and aryl bromides in very good isolated yields.
S. Montel, L. Raffier, Y. He, P. J. Walsh, Org. Lett., 2014,
16, 1446-1449.
A Rh(III)-catalyzed cascade arylation and chlorination of α-diazocarbonyl
compounds with arylboronic acids and N-chlorosuccinimide exhibits
excellent functional group tolerance on the organoboron and the diazo reagents.
Functionalized α-aryl-α-chlorocarbonyl compounds were obtained in good yields.
F.-N. Ng, Y.-F. Lau, Z. Zhou, W.-Y. Yu, Org. Lett.,
2015,
17, 1676-1679.
An efficient, mild, and general method for the C-arylation of β-enamino
esters and ketones with arynes provides a facile and direct access to various
substituted aromatic β-enamino compounds in good yield.
Y. K. Ramtohul, A. Chartrand, Org. Lett., 2007,
9, 1029-1032.
An efficient α-arylation of imino amides with arylboronic acids provides an
alternative approach for the synthesis of α-functionalized glycine derivatives.
Different substrates were examined for this arylation reaction.
L. Zhao, X. Liao, C.-J. Li, Synlett, 2009, 2953-2956.
CuO catalyzes a three-component reaction of α-ketoaldehydes, 1,3-dicarbonyl
compounds, and organic boronic acids in water to provide a wide range of
products containing 1,3- and 1,4-diketones. The method offers use of readily
available starting materials, wide substrate scope, excellent yields, gram-scale
synthesis, and mild reaction conditions.
Q. Xia, X. Li, X. Fu, Y. Zhou, Y. Peng, J. Wang, G. Song, J. Org. Chem., 2021, 86,
9914-9923.
Cu-catalyzed asymmetric conjugate reduction of
β-substituted ketones leads to enantiomerically enriched
diphenylsilyl enol ethers, which are utilized in a diastereoselective Pd-catalyzed
α-arylation of various aryl bromides to yield disubstituted cycloalkanones with
excellent levels of enantiomeric and diastereomeric purity. The procedure can be
carried out in one-pot.
J. Chae, J. Yun, S. L. Buchwald, Org. Lett., 2004, 6, 4809-4812.
A very simple method for the α-arylation of N-protected
2-piperidinones in high yield is described. Key factors are the use of ZnCl2 and
Pd(dba)2 and the nature of the base.
A. de Filippis, D. G. Pardo, J. Cossy, Tetrahedron, 2004,
60,
9757-9767.
Chiral N-heterocyclic carbene (NHC) ligands having a 2,2′-bisquinoline-based
C2 symmetric skeleton exhibited good enantioselectivity in
palladium-catalyzed intramolecular α-arylation of amides to give
3,3-disubsituted oxindoles.
L. Liu, N. Ishida, S. Ashida, M. Murakami, Org. Lett., 2011,
13, 1666-1669.
A catalyst generated from Pd(dba)2 and a bulky electron-rich phosphine
ligand is
effective for the α-arylation of oxindoles. Generation of the potassium-enolates
of a range of oxindoles enables the coupling with aryl chlorides, bromides, and
triflates.
M. J. Durbin, M. C. Willis, Org. Lett.,
2008, 10, 1413-1415.
A small library of α,β-unsaturated oxindoles was
prepared by an efficient microwave-assisted one-pot sequence comprising an
aromatic substitution followed by an ionic Horner-Wadsworth-Emmons olefination.
A. Teichert, K. Jantos, K. Harms, A. Studer, Org. Lett., 2004,
6, 3477-3480.
Related
The use of an oxazaborolidinium ion catalyst enables a highly stereoselective
synthesis of (Z)-silyl enol ethers from alkyl aryl ketones and
trimethylsilyldiazomethane (TMSD). The conversion of cyclic ketones gives
ring-expanded silyl enol ethers.
B. Chul, Kang, S. Y. Shim, D. H. Ryu, Org. Lett., 2014,
16, 2077-2079.
A sequential hydroboration/Suzuki-Miyaura coupling of ynol ethers allows a
highly regio- and stereoselective synthesis of stereodefined β,β-disubstituted
alkenyl ethers. A number of functional groups are well-tolerated under the
reaction conditions. Furthermore, the reaction enables a facile entry to labile
diarylacetaldehydes by TFA-mediated hydrolysis of the β,β-disubstituted vinyl
ethers.
W. Cui, M. Mao, Z. He, G. Zhu, J. Org. Chem., 2013,
78, 9815-9821.
DavePhos as ligand efficiently promotes a palladium-catalyzed Heck reaction
between 2-oxyacrylates and aryl bromides to provide 2-oxycinnamates, which serve
as excellent precursors for the synthesis of monoaryl pyruvates or ortho
ester-protected monoaryl pyruvates depending on the nature of the 2-oxy group.
K. Matcha, K. Chernichenko, K. Jouvin, S. B. Guduguntla, D. N. Tran, S. Bell,
W. Paden, M. Figlus, C. Muir, C. H. Diaz, J. Org. Chem., 2022, 87,
10736-10746.
Functionalized α-tertiary and -quaternary 2-arylcycloalkanones are rapidly
accessed by scandium(III) triflate-catalyzed diazoalkane-carbonyl homologations.
Pairing readily available bis- and tris(oxazoline) based ligands with scandium
triflate allows access to arylated medium ring carbocycles with high
enantioselectivities and excellent yield.
V. L. Rendina, H. Z. Kaplan, J. S. Kingsbury, Synthesis, 2012, 44,
686-693.
V. L. Rendina, H. Z. Kaplan, J. S. Kingsbury, Synthesis, 2012, 44,
686-693.
 |
Palladium-catalyzed
alpha-Arylation of Esters, Ketones, Amides and Imides |