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1,4-Addition and similar reactions

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A mild and efficient Pd(II)-catalyzed conjugate addition of arylboronic acids to α,β-unsaturated carbonyl compounds, aldehydes, esters, and amides in the presence of 2,2'-bipyridine was developed. The mechanism and the role of the bipyridine are discussed.
X. Lu, S. Lin, J. Org. Chem., 2005, 70, 9651-9653.

A practical method for the one-step preparation of 3-arylpropionic acids through rhodium-catalyzed 1,4-addition of arylboronic acids to acrylic acid is applicable to a broad scope of aryl boronic acids and displays a wide functional group tolerance operating in water as the optimal reaction medium.
N. R. Vautravers, B. Breit, Synlett, 2011, 2517-2520.

A chelated Pd(II) complex catalyzes a coupling of organoborane reagents with cyclopropanol-derived β-ketone enolates to provide synthetically important β-aryl ketone intermediates in a chemoselective fashion.
T. Ramar, M. A. M. Subbaiah, A. Ilangovan, J. Org. Chem., 2020, 85, 7711-7727.

A mild and convenient Pd(II)/bipyridine-catalyzed conjugate addition of arylboronic acids to α,β-unsaturated carboxylic acids provides β-substituted carboxylic acids including highly challenging β-quaternary carbons.
R. Liu, Z. Yang, Y. Ni, K. Song, K. Shen, S. Lin, Q. Pan, J. Org. Chem., 2017, 82, 8023-8030.

2-methyl-1,3-propenylene-bridged (η5-diarylphosphinocyclopentadienyl)(phosphine)manganese(I) dicarbonyl complexes show better robustness as well as higher enantioselectivity over phosphine-olefin ligands with a planar-chiral (η6-arene)chromium(0) framework in rhodium-catalyzed 1,4-additions of arylboronic acids to various cyclic/acyclic enones and asymmetric 1,2-additions of arylboron nucleophiles to imines or aldehydes.
K. Kamikawa, Y.-Y. Tseng, J.-H. Jian, T. Takahashi, M. Ogasawara, J. Am. Chem. Soc., 2017, 139, 1545-1553.

Anionic four-electron donor-based palladacycles were highly efficient, practical catalysts for 1,4-additions of arylboronic acids with α,β-unsaturated ketones and 1,2-additions of arylboronic acids with aldehydes and α-ketoesters.
P. He, Y. Lu, C.-G. Dong, Q.-S. Hu, Org. Lett., 2007, 9, 343-346.

A simple and efficient Ru-catalyzed conjugate addition reaction of arylboronic acids to α,β-unsaturated ketones under neutral conditions without any additional ligands both fulfilled the inhibition of the β-hydride elimination in the catalytic cycle and minimized the protonolysis of arylboronic acids.
L. Zhang, X. Xie, L. Fu, Z. Zhang, J. Org. Chem., 2013, 78, 3434-3437.

An air-stable phosphinito complex of palladium(II) catalyzed the Heck coupling of aryl bromides with primary and secondary allylic alcohols to give carbonyl compounds. Reactions with tertiary allylic alcohols under the same conditions generated the aromatic conjugated alcohols.
A. Sauza, J. A. Morales-Serna, M. García-Molina, R. Gaviño, J. Cárdenas, Synthesis, 2012, 44, 272-282.

Copper complexes of phosphoramidites efficiently catalyzed asymmetric addition of arylboron reagents to acyclic enones. 1,4-Insertion of arylcopper(I) led directly to O-bound copper enolates, which makes the mechanism fundamentally different from classical oxidative addition/reductive elimination.
C. Wu, G. Yue, C. D.-T. Nielsen, K. Xu, H. Hirao, J. Zhou, J. Am. Chem. Soc., 2016, 138, 742-745.

Chiral anion phase transfer enables an asymmetric Heck-Matsuda reaction of acyclic alkenyl alcohols to provide various chiral ketones in high levels of enantioselectivity. A catalytic amount of dimethyl sulfoxide (DMSO) as an additive is crucial to suppress palladium-hydride-mediated side reactions.
T. Zhang, W.-A. Li, H.-C. Shen, S.-S. Chen, Z.-Y. Han, Org. Lett., 2021, 23, 1473-1477.

A nickel complex of isoquinox promoted enantioselective conjugate arylation and heteroarylation of enones using aryl and heteroaryl halides directly. Experiments and calculations supported an insertion of an arylnickel(I) complex to enones via an elementary 1,4-addition.
L. Zhang, M. Zhao, M. Pu, Z. Ma, J. Zhou, C. Chen, Y.-D. Wu, Y. R. Chi, J. S. Zhou, J. Am. Chem. Soc., 2022, 144, 20249-20257.

Palladium-phosphinous acids catalyze the microwave-assisted conjugate addition of arylsiloxanes to a wide range of α,β-unsaturated substrates in water. The described procedure eliminates the need for stoichiometric additives and an excess of arylsiloxane, and does not require an inert atmosphere.
R. Lerebours, C. Wolf, Org. Lett., 2007, 9, 2737-2740.

Photoredox/nickel dual catalysis enables a cross-coupling of secondary alkyl β-trifluoroboratoketones and -esters with aryl bromides. Reactions occur under mild conditions, and various functional groups and sterically and electronically diverse reaction partners are tolerated.
J. C. Tellis, J. Amani, G. A. Molander, Org. Lett., 2016, 18, 2994-2997.

Ketone-, ester-, and amide-containing potassium trifluoroboratohomoenolates were prepared in good yields from the corresponding unsaturated carbonyl compounds. They are effective coupling partners in the Suzuki-Miyaura reaction with various electrophiles including electron-rich and electron-poor aryl bromides and -chlorides.
G. A. Molander, D. E. Petrillo, Org. Lett., 2008, 10, 1795-1798.

A mild palladium catalyzed coupling of reactive aldehyde homoenolates, that are generated by ring opening of cyclopropanols, with aryl bromides gives aldehyde products at room temperature in good yield.
K. Cheng, P. J. Walsh, Org. Lett., 2013, 15, 2298-2301.

A Pd-catalyzed arylation of 1,2-amino alcohols with aryl halides provides β-arylated aldehydes via in situ generated enamine intermediates. The protocol is characterized by its exquisite regioselectivity profile and broad substrate scope - including challenging substrate combinations - even in an enantioselective manner.
M. Sau, M. A. Pericàs, R. Martin, Synlett, 2022, 33, 52-56.

Conjugate addition of α,β-unsaturated ketones with arylzinc species, that were formed in situ from diethylzinc and a series of arylboronic acids by boron-zinc exchange reactions, gave 1,4-addition products in good yields.
L. Dong, Y.-J. Xu, L.-Z. Gong, A.-Q. Mi, Y.-Z. Jiang, Synthesis, 2004, 1015-1020.

A conjugate addition of various aryl halides and triflates to Michael acceptors is efficiently catalyzed by CoBr2(2,2'-bipyridine). The described procedure allows for the synthesis of 1,4-addition products in good yields.
M. Amatore, C. Gosmini, J. Périchon, J. Org. Chem., 2006, 71, 6130-6134.

M. Amatore, C. Gosmini, J. Périchon, J. Org. Chem., 2006, 71, 6130-6134.

The compatibility of two metal complexes (Au/Rh) and their orthogonal ligand systems (NHC/diene) in a bimetallic catalytic system enables an asymmetric one-pot tandem Au/Rh-catalyzed synthesis of highly enantioenriched β-disubstituted ketones starting from racemic propargyl alcohols.
M. M. Hansmann, A. S. K. Hashmi, M. Lautens, Org. Lett., 2013, 15, 3226-3229.

Asymmetric Rh-catalyzed 1,4-addition of arylboronic acids to α,β-unsaturated carbonyl compounds proceeded smoothly to afford the corresponding β-arylated products in excellent yields and outstanding enantioselectivities with wide substrate scope. Remarkably, a chiral metal nanoparticle system showed performance in terms of yield, enantioselectivity, and catalytic turnover that was superior. This catalyst can be recovered and reused.
T. Yasukawa, A. Suzuki, H. Miyamura, K. Nishino, S. Kobayashi, J. Am. Chem. Soc., 2015, 137, 6616-6623.

Electron-poor chiral diphosphine ligands were synthesized for controlling a transition-metal catalyst electronically. A ligated Rh catalyst showed excellent catalytic activity with high % ee for asymmetric 1,4-addition of arylboronic acids to α,β-unsaturated carbonyls at 20°C.
T. Korenaga, K. Osaki, R. Maenishi, T. Sakai, Org. Lett., 2009, 11, 2325-2328.

The conjugate addition of arylboronic acids to α,β-unsaturated amides was carried out in the presence of a chiral rhodium catalyst prepared in situ from Rh(acac)(CH2CH2)2 and (S)-binap. Addition of an aqueous base was highly effective to improve the chemical yields via formation of a RhOH species, that is active for transmetalation with arylboronic acids.
S. Sakuma, N. Miyaura, J. Org. Chem., 2001, 66, 8944-8946.

A nickel-catalyzed conjunctive cross-coupling of simple alkenyl amides with aryl iodides and aryl boronic esters delivers the desired 1,2-diarylated products with excellent regiocontrol. The reaction is enabled by an electron-deficient olefin (EDO) ligand. Under optimized conditions, a wide range of amides derived from 3-butenoic acid, 4-pentenoic acid, and allyl amines are compatible substrates.
J. Derosa, R. Kleinmans, V. T. Tran, M. K. Karunananda, S. R. Wisniewski, M. D. Eastgate, K. M. Engle, J. Am. Chem. Soc., 2018, 140, 17878-17883.

A chiral bicyclic bridgehead phosphoramidite (briphos) ligand derived from 1-aminoindane was efficient for the Rh-catalyzed enantioselective 1,2-arylation of N-sulfonyl imines, while that derived from 1,2,3,4-tetrahydro-1-naphthylamine was efficient for 1,4-arylation of α,β-unsaturated cyclic ketones. For α,β-unsaturated N-tosyl ketimines, the briphos derived from 1-aminoindane selectively provided γ,γ-diaryl N-tosyl enamines.
A. Lee, H. Kim, J. Org. Chem., 2016, 81, 3520-3527.

A chiral diene possessing the bicyclo[2.2.2]octadiene framework substituted with a tertiary alcohol on one of the two double bonds is readily prepared in two steps and is highly effective as a chiral ligand for rhodium-catalyzed asymmetric conjugate addition reactions, giving the corresponding addition products with high enantioselectivity.
K. Okamoto, T. Hayashi, V. H. Rawal, Org. Lett., 2008, 10, 4387-4389.

An in situ generated chiral rhodium-binap-based catalyst enables a practical method for the asymmetric Michael addition of arylboronic acids to α,β-unsaturated carbonyl compounds, while maintaining high levels of enantioselectivity. Substantial reductions in both the boronic acid and the catalyst loads are achieved.
K. Lukin, Q. Zhang, M. R. Leanna, J. Org. Chem., 2009, 74, 929-931.

Various enantioenriched tert-butyl 3,3-diarylpropanoates are prepared via an asymmetric rhodium-catalyzed conjugate addition of arylboronic acids to unsaturated tert-butyl esters in the presence of chiral dienes as ligands.
J.-F. Paquin, C. R. J. Stephenson, C. Defieber, E. M. Carreira, Org. Lett., 2005, 7, 3821-3824.

The C2-symmetric norbornadiene derivative (1R,4R)-2,5-dibenzylbicyclo[2.2.1]hepta-2,5-diene was used as ligand for the rhodium-catalyzed asymmetric 1,4-addition of organoboron and -tin reagents to α,β-unsaturated ketones, which gave high yields of the addition products with up to 99% enantioselectivity.
T. Hayashi, K. Ueyama, N. Tokunaga, K. Yoshida, J. Am. Chem. Soc., 2003, 125, 11508-11509.

An additive-free, clean conjugate addition reaction of organosiloxanes to α,β-unsaturated compounds is catalyzed by a cationic rhodium complex in dioxane/water. The mechanism involves a transmetalation step between the rhodium complex and the silicon reagent.
S. Oi, Y. Honma, Y. Inoue, Org. Lett., 2002, 4, 667-669.

A conjugate addition of organosiloxanes to α,β-unsaturated carbonyl compounds catalyzed by a cationic rhodium complex generated from [Rh(cod)(MeCN)2]BF4 and (S)-BINAP in dioxane/water gave products in good yields and excellent enantioselectivities.
S. Oi, A. Taira, Y. Honma, Y. Inoue, Org. Lett., 2003, 5, 97-99.

Rhodium-catalyzed conjugate addition of arylboronic acids to various 4-oxobutenamides provides oxobutanamides with high regio- and enantioselectivity and good yields in the presence of sterically demanding P-chiral diphosphines, such as Tangphos or Duanphos.
J. L. Zigterman, J. C. S. Woo, S. D. Walker, J. S. Tedrow, C. J. Borths, E. E. Bunel, M. M. Faul, J. Org. Chem., 2007, 72, 8870-8876.

A chiral bicyclic bridgehead phosphoramidite (briphos) is a highly efficient and selective ligand for Rh(I)-catalyzed asymmetric 1,4-addition of arylboronic acids to α,β-unsaturated N,N-dimethyl-sulfamoyl imino esters at ambient temperature providing chiral (Z)-γ,γ-diaryl-α,β-dehydroamino esters with excellent yield and enantioselectivity, that can be further converted to unnatural amino acids, hydroxy ketones, and keto acids.
A. Lee, H. Kim, J. Am. Chem. Soc., 2015, 137, 11250-11253.

The first enantioselective organocatalytic alkylation of electron-rich benzene rings with α,β-unsaturated aldehydes using iminium catalysis has provided a new strategy for the enantioselective construction of benzylic stereogenicity. The (2S,5S)-5-benzyl-2-tert-butylimidazolidinone amine catalyst has been found to mediate the conjugate addition of a wide variety of substituted and unsubstituted anilines to a diverse spectrum of unsaturated aldehydes.
N. A. Paras, D. W. C. MacMillan, J. Am. Chem. Soc., 2002, 124, 7894-7895.

A rhodium complex coordinated with (S,S)-2,5-dibenzylbicyclo[2.2.2]octa-2,5-diene (Bn-bod*) showed high catalytic activity and high enantioselectivity in the asymmetric 1,4-addition of arylboroxines to α,β-unsaturated ketones.
F.-X. Chen, A. Kina, T. Hayashi, Org. Lett., 2006, 8, 341-344.

An enantioselective, rhodium-catalyzed 1,4-addition of arylboronic acids to β-silyl α,β-unsaturated carbonyl compounds has been developed employing (R,R)-Bn-bod* as a ligand, which allows the synthesis of various β-silyl 1,4-adducts in very high enantiomeric excess.
R. Shintani, K. Okamoto, T. Hayashi, Org. Lett., 2005, 7, 4757-4759.

By using a hydrophilic bicyclo[3.3.0] diene ligand, a Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to α,β-unsaturated carbonyl compounds can be performed successfully in water at room temperature to afford the corresponding products in good yields and with very high enantioselectivities for both cyclic and linear substrates.
C.-G. Feng, Z.-Q. Wang, C. Shao, M.-H. Xu, G.-Q. Lin, Org. Lett., 2008, 10, 4101-4104.

Two new atropisomeric electron-poor chiral diphosphine ligand analogues of SYNPHOS were prepared, that allow a highly performant Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to α,β-unsaturated carbonyl compounds at room temperature.
F. Berhal, O. Esseiva, C.-H. Martin, H. Tone, J.-P. Genet, T. Ayad, V. Ratovelomanana-Vidal, Org. Lett., 2011, 13, 2806-2809.

Ligand-free cationic Pd(II) catalyst is a highly active catalytic system for conjugate additions of boroxines to sterically hindered γ-substituted cyclohexenones in the presence of NaNO3 as an additive. More challenging γγ- and βγ-substrates also react well to produce products with quaternary centers in a highly diastereoselective fashion.
J. A. Jordan-Hore, J. N. Sanderson, A.-L. Lee, Org. Lett., 2012, 14, 2508-2511.

C.-G. Feng, Z.-Q. Wang, C. Shao, M.-H. Xu, G.-Q. Lin, Org. Lett., 2008, 10, 4101-4104.

Cu-catalyzed enantioselective conjugate additions of alkyl- and arylzinc reagents to unactivated cyclic β-substituted enones are promoted in the presence of 2.5-15 mol% of a readily available chiral NHC-based Cu complex, affording the desired products bearing all-carbon quaternary stereogenic centers in good yield and enantioselectivity.
K.-S. Lee, M. K. Brown, A. W. Hird, A. H. Hoveyda, J. Am. Chem. Soc., 2006, 128, 7182-7184.

The reaction of different functionalised organolithium compounds prepared by DTBB-catalysed lithiation of isochromane, phthalane, 2,3-dihydrobenzofuran and 1-chloro-3,3-diethoxypropane with an equimolecular amount of zinc bromide, followed by reaction with an aryl or an alkenyl bromide in the presence of a palladium catalyst gives the expected cross-coupling products.
M. Yus, J. Gomis, Eur. J. Org. Chem., 2002, 1989-1995.

Potassium trifluoro(organo)borates, which are highly stable and easily prepared organoboron derivatives, were able to react with various dehydroamino esters to alanine derivatives in good to high yields. This reaction, catalyzed by rhodium complexes, tolerates a great variety of amino protecting groups.
L. Navarre, S. Darses, J.-P. Genet, Eur. J. Org. Chem., 2004, 69-73.

Rhodium-catalyzed conjugate addition of potassium trifluoro(organo)borates to dehydroalanine derivatives, using chiral ligands such as fluorophos and in situ enantioselective protonation with guaiacol (2-methoxyphenol), afforded a variety of protected α-amino esters with high yields and enantiomeric excesses up to 95%.
L. Navarre, R. Martinez, J.-P. Genet, S. Darses, J. Am. Chem. Soc., 2008, 130, 6159-6169.

iPr-IsoQuinox as a chiral ligand enables a palladium-catalyzed asymmetric addition of arylboronic acids to nitrostyrene in MeOH as solvent under an air atmosphere providing chiral diarylsubstituted products in high yields with good enantioselectivities. A broad range of substrates can be used.
Q. He, F. Xie, G. Fu, M. Quan, C. Shen, G. Yang, I. D. Gridnev, W. Zhang, Org. Lett., 2015, 17, 2250-2253.

An efficient enantioselective addition of an array of arylboronic acids to various β-nitrostyrenes is catalyzed by a novel and reactive rhodium-diene catalyst and provides β,β-diarylnitroethanes in very good yields with excellent enantioselectivities. Additions to 2-heteroarylnitroolefins and 2-cycloalkylnitroolefins similarly provide the desired products with high enantioselectivities and yields.
K.-C. Huang, B. Gopula, T.-S. Kuo, C.-W. Chiang, P.-Y. Wu, J. P. Henschke, Hsyueh-Liang Wu, Org. Lett., 2013, 15, 5730-5733.

In an efficient rhodium/olefin-sulfoxide catalyzed asymmetric conjugate addition of organoboronic acids to nitroalkenes, 2-methoxy-1-naphthyl sulfinyl functionalized olefin ligands are highly effective and applicable to a broad scope of aryl, alkyl, and heteroaryl nitroalkenes.
F. Xue, D. Wang, X. Li, B. Wan, J. Org. Chem., 2012, 77, 3071-3081.

Asymmetric addition of arylboronic acids to α,β-unsaturated sulfonyl compounds proceeded in the presence of a rhodium catalyst coordinated with a chiral diene ligand to give high yields of the addition products with high enantioselectivity. The diene ligand was proved to be essential for the formation of the addition products.
T. Nishimura, Y. Takiguchi, T. Hayashi, J. Am. Chem. Soc., 2012, 134, 9086-9089.

An efficient asymmetric 1,4-addition of arylboronic acids to β-phthaliminoacrylate esters was realized by use of a hydroxorhodium/chiral diene complex to give high yields of β-aryl-β-amino acid esters with excellent enantioselectivity.
T. Nishimura, J. Wang, M. Nagaosa, K. Okamoto, R. Shintani, F.-y. Kwong, W.-y. Yu, A. S. C. Chan, T. Hayashi, J. Am. Chem. Soc., 2010, 132, 464-465.

The reaction of 3-sulfolene with arylboronic acids in the presence of a chiral diene-rhodium catalyst under highly basic conditions gave high yields of 3-arylsulfolanes with high enantioselectivity via a base-catalyzed isomerization to the more reactive 2-sulfolene.
K. M.-H. Lim, T. Hayashi, J. Am. Chem. Soc., 2015, 137, 3201-3204.

The precatalyst [{(P,Rs,Rs)-p-tol-BINASO}RhCl]2, which can be synthesized from relatively cheap, commercially available starting materials, shows both excellent reactivity and selectivity in the asymmetric 1,4-addition of arylboronic acids to cyclic α,β-unsaturated ketones and esters.
R. Mariz, X. Luan, M. Gatti, A. Linden, R. Dorta, J. Am. Chem. Soc., 2008, 130, 2172-2173.

Novel chiral phosphine-olefin ligands have been designed, which act as bidentates in an efficient rhodium-catalyzed asymmetric 1,4-addition of aryl boronic acids to maleimides.
R. Shintani, W.-L. Duan, T. Nagano, A. Okada, T. Hayashi, Angew. Chem. Int. Ed., 2005, 44, 4611-4614.

R. Shintani, W.-L. Duan, T. Nagano, A. Okada, T. Hayashi, Angew. Chem. Int. Ed., 2005, 44, 4611-4614.


A cooperative catalyst system enhances both yield and selectivity of an enantioselective N-heterocyclic carbene (NHC)-catalyzed β-protonation providing a broad range of aryl-oxobutenoates and highly enantioenriched succinate derivatives. The method demonstrates the benefits of combining different activation modes in organocatalysis.
M. H. Wang, D. T. Cohen, C. Benjamin Schwamb, R. K. Mishra, K. A. Scheidt, J. Am. Chem. Soc., 2015, 137, 5891-5894.

Very efficient reactions of Baylis-Hillman adducts with iodobenzenes using commercially available palladium-on-carbon as a catalyst under solvent-free conditions afforded α-benzyl-β-keto esters in very good yields.
H.-S. Kim, S.-J. Lee, B. Choi, C. M. Yoon, Synthesis, 2012, 44, 3161-3164.

An improved Heck reaction allows the synthesis of various α-benzyl-β-keto esters from aryl bromides and Baylis-Hillman adducts for use in the preparation of new pharmaceutical agents.
N. J. Bennett, A. Goldby, R. Pringle, Synlett, 2010, 1688-1690.