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Synthesis of substituted carboxylic acids, esters and amides


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An efficient cobalt-catalyzed reductive coupling reaction of alkyl halides with alkenes bearing electron-withdrawing groups in the presence of water and zinc powder in acetonitrile gave the corresponding Michael-type addition products in high yields. The mechanism is discussed.
P. Shukla, Y.-C. Hsu, C.-H. Cheng, J. Org. Chem., 2006, 71, 655-658.

Tin-free Giese reaction of alkyl iodides with electron-deficient alkenes and the related radical carbonylation process proceeded efficiently in the presence of sodium cyanoborohydride and tetrabutylammonium cyanoborohydride. Transfer of iodine followed by hydride reduction of the resulting carbon-iodine bond is proposed as a possible mechanism.
I. Ryu, S. Uehara, H. Hirao, T. Fukuyama, Org. Lett., 2008, 10, 1005-1008.

Formation of alkyl radicals via activation of alkyl bromides through cobalt/iridium catalysis enables a reductive radical conjugate addition under mild and less toxic conditions. The reaction conditions tolerate benzylic halides and halides containing free alcohols, silanes, and chlorides.
R. A. Escobar, J. W. Johannes, Org. Lett., 2021, 23, 6046-6051.

TiIII catalysis enables a radical addition of unactivated 2° and 3° alkyl chlorides to electron-deficient alkenes, while primary alkyl chlorides or aryl bromides remain untouched. This method offers a new route to C-C bond formation that is complementary to existing protocols.
X. Wu, W. Hao, K.-Y. Ye, B. Jiang, G. Pombar, Z. Song, Song Lin, J. Am. Chem. Soc., 2018, 140, 14836-14843.

A direct dehydroxylative radical alkylation reaction of tertiary alcohols with activated alkenes enables a facile and precise construction of all-carbon quaternary centers. The reaction tolerates a wide range of electrophilic coupling partners, including allylic carboxylates, aryl and vinyl electrophiles, and primary alkyl chlorides/bromides and leaves secondary/primary alcohols and phenols intact.
H. Xie, J. Guo, Y.-G. Wang, K. Wang, P. Guo, P.-F. Su, X. Wang, X.-Z. Shu, J. Am. Chem. Soc., 2020, 142, 16787-16794.

The formation of an alkyl thianthrenium salt/Hantzsch ester electron donor-acceptor complex enables a photocatalyst- and metal-free generation of an alkyl radical and a subsequent C(sp3)-C(sp3) bond formation with activated olefins. This protocol tolerates a broad range of functionality and can successfully be used in late-stage functionalization of pharmaceuticals.
X. Li, W. Si. Z. Liu, H. Qian, T. Wang, S. Leng, J. Sun, Y. Jiao, X. Zhang, Org. Lett., 2022, 24, 4070-4074.

CuCl2 catalyzes a coupling of unactivated C(sp3)-H bonds of numerous feedstock chemicals with electron-deficient olefins. The active cuprate catalyst undergoes Ligand-to-Metal Charge Transfer (LMCT) to enable the generation of a chlorine radical which acts as a powerful hydrogen atom transfer reagent capable of abstracting strong electron-rich C(sp3)-H bonds.
S. M. Treacy, T. Rovis, J. Am. Chem. Soc., 2021, 143, 2729-2735.

Photoredox catalysis enables a decarbonylation of alkyl-substituted acyl radicals. In a photoredox 1,4-conjugate addition of alkyl ketoacids to electrophilic alkenes, tertiary alkyl ketoacids have proved to be good precursors.
J.-Q. Chen, R. Chang, Y.-L. Wei, J.-N. Mo, Z.-Y. Wang, P.-F. Xu, J. Org. Chem., 2018, 83, 253-259.

Under mild and redox-neutral reaction conditions, a photocatalytic dehydroxymethylation in the presence of a cerium catalyst enabled the direct utilization of primary alcohols as unconventional alkyl nucleophiles for radical-mediated 1,4-additions with Michael acceptors. The modularity of this catalytic system has been demonstrated in hydrogenation, amination, alkenylation, and oxidation.
K. Zhang, L. Chang, Q. An, X. Wang, Z. Zuo, J. Am. Chem. Soc., 2019, 141, 10556-10564.

Anatase titanium dioxide (TiO2) mediates a versatile method for the hydromethylation and hydroalkylation of alkenes at room temperature. The photoexcitation of TiO2 with 390 nm light in the presence of acetic acid and other carboxylic acids generates methyl and alkyl radicals, respectively.
Q. Zhu, D. G. Nocera, J. Am. Chem. Soc., 2020, 142, 17913-17918.

Inexpensive and readily available Grignard reagents and stable dinuclear Cu complexes can be used for the catalytic enantioselective conjugate addition to simple acyclic α,β-unsaturated methyl esters providing β-substituted chiral esters in good yields and with excellent enantioselectivities.
F. Lopez, S. R. Harutyunyan, A. Meetsma, A. J. Minnaard, B. L. Feringa, Angew. Chem. Int. Ed., 2005, 44, 2752-2756.

F. Lopez, S. R. Harutyunyan, A. Meetsma, A. J. Minnaard, B. L. Feringa, Angew. Chem. Int. Ed., 2005, 44, 2752-2756.

A highly efficient regio- and enantioselective catalytic asymmetric addition of Grignard regeants to α,β-unsaturated esters is promoted by the CuI-Tol-BINAP system.
S.-Y. Wang, S.-J. Ji, T.-P. Loh, J. Am. Chem. Soc., 2007, 129, 276-277.

A highly efficient regio- and enantioselective catalytic asymmetric addition of Grignard regeants to α,β-unsaturated esters is promoted by the CuI-Tol-BINAP system.
S.-Y. Wang, S.-J. Ji, T.-P. Loh, J. Am. Chem. Soc., 2007, 129, 276-277.

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.

A nickel catalyst system for 1,4-addition of trialkylboranes to α,β-unsaturated esters has been developed. For the alkylation reaction with 9-alkyl-9-BBNs, addition of methanol was found to be essential.
K. Hirano, H. Yorimitsu, K. Oshima, Org. Lett., 2007, 9, 1541-1544.

Pyrimidopteridine N-oxides as organic photoredox-active catalysts mediate a metal-free photoinduced decarboxylative Giese-type addition of carboxylic acids to a variety of electron-deficient alkenes.
F. El-Hage, C. Schöll, J. Pospech, J. Org. Chem., 2020, 85, 13853-13867.

When used with photocatalysis, bench-stable, commercially available collidinium salts are excellent radical precursors with a broad scope, that can substitute alkyl halides. Furthermore, all of the reaction components are water-soluble, which facilitates product isolation.
M. D. Rathnayake, J. D. Weaver III, Org. Lett., 2021, 23, 2036-2041.

A photoredox/nickel dual catalytic protocol enables a regioselective three-component carboacylation of alkenes with tertiary and secondary alkyltrifluoroborates as well as acyl chlorides. This redox-neutral protocol can be applied to the rapid synthesis of ketones with high diversity and complexity via a radical relay process. Many functional groups are tolerated under the mild conditions.
Z.-K. Wang, Y.-P. Wang, Z.-W. Rao, C.-Y. Liu, X.-H. Pan, L. Guo, Org. Lett., 2023, 25, 1673-1677.

Copper(II)-mediated ring opening/alkynylation of cyclopropanols with inexpensive and commercially available terminal alkynes proceeded efficiently to afford synthetically useful alk-4-yn-1-ones in good yields with good functional group tolerance.
B.-Q. Cheng, S.-X. Zhang, Y.-Y. Cui, X.-Q. Chu, W. Rao, H. Xu, G.-Z. Han, Z.-L. Shen, Org. Lett., 2020, 22, 5456-5461.

NHC/palladium cooperative catalysis enables a highly stereoselective umpolung 1,4-addition of vinyl bromides to enals to provide various valuable γ,δ-unsaturated carbonyl derivatives in excellent yields. The NHC acts as both organocatalyst and ligand for palladium.
B. Ling, W. Yang, Y.-E. Wang, J. Mao, Org. Lett., 2020, 22, 9603-9608.

A nickel-catalyzed three-component reductive alkylacylation of electron-deficient activated alkenes with acid anhydrides and tertiary alkyl bromides enables the efficient preparation of a variety of ketones with broad substrate scope and high functionality tolerance starting from simple precursors.
L. Wang, C. Wang, Org. Lett., 2020, 22, 8829-8835.

In a synergistical combination of photoredox catalysis and organocatalysis for the direct β-alkylation of saturated aldehydes, photon-induced enamine oxidation provides an activated β-enaminyl radical intermediate, which readily combines with a wide range of Michael acceptors to produce β-alkyl aldehydes in a highly efficient manner. This redox-neutral, atom-economical C–H functionalization can be achieved both inter- and intramolecularly.
J. A. Terrett, M. D. Clift, D. W. C. MacMillan, J. Am. Chem. Soc., 2014, 136, 6858-6861.

Depending on the Lewis base catalyst, a Michael addition of α-aminonitriles to simple activated alkenes provides functionalized γ-amino acid esters or γ-lactams. The scope, versatility, and efficiency of the methods were demonstrated.
Z.-Y. He, H.-C. Jang, L.-S. Teng, Z.-L. Wei, W.-W. Liao, Synthesis, 2021, 53, 1833-1841.

1,2-Bis-boronic esters are versatile intermediates that enable the rapid elaboration of simple alkene precursors. A photoredox-catalyzed mono-deboronation generates primary β-boryl radicals that undergo rapid 1,2-boron shift to form thermodynamically favored secondary radicals, allowing for selective transformation of the more hindered boronic ester.
D. Kaiser, A. Noble, V. Fasano, V. K. Aggarwal, J. Am. Chem. Soc., 2019, 141, 14104-14109.

The use of Me-StackPhos as ligand enables a Cu-catalyzed enantioselective conjugate alkynylation of Meldrum’s acid acceptors. The reaction tolerates a wide range of alkynes furnishing highly useful β-alkynyl Meldrum's acid building blocks in high yields and excellent enantioselectivity.
S. Mishra, J. Liu, A. Aponick, J. Am. Chem. Soc., 2017, 139, 3352-3355.

An operationally simple and scalable Cu-catalyzed asymmetric conjugate addition of trialkenylboroxines to enone diesters proceeded at room temperature. Mechanistic studies revealed that two different catalytic species work synergistically in the reaction.
K. Yasumoto, N. Kunitomo, T. Kano, Org. Lett., 2023, 25, 1497-1502.

A (Salen)Al-Cl complex catalyzes the asymmetric conjugate addition of hydrogen cyanide to α,β-unsaturated imides in high yields and enantioselectivities. The cyanide adducts can readily be converted into a variety of useful chiral building blocks, including α-substituted-β-amino acids.
G. M. Sammis, E. N. Jacobsen, J. Am. Chem. Soc., 2003, 125, 4442-4443.

Chiral complexes of calcium promote asymmetric 1,4-addition reactions and [3+2] cycloaddition reactions of α-amino acid derivatives with α,β-unsaturated carbonyl compounds. The reactions proceeded smoothly in the presence of 5-10 mol % of the chiral calcium catalyst to afford the desired adducts in high yields with high diastereo- and enantioselectivities.
S. Saito, T. Tsubogo, S. Kobayashi, J. Am. Chem. Soc., 2007, 129, 5364-5365.

The conversion of β-keto esters into β-methylated and phenylated γ-keto esters can be achieved through treatment with zinc carbenoids derived­ from 1,1-diiodoethane and diiodotoluene, respectively.
W. Lin, R. J. McGinness, E. C. Wilson, C. K. Zercher, Synthesis, 2007, 2404-2408.

A TiCl4-Mg promoted coupling of various amides with CH2Cl2 and methyl acrylate allows an extremely simple and practical synthesis of 1,5-keto esters. The efficiency of this chemistry is illustrated by the very simple preparation of unusual 4,4-dideuterio-1,5-keto esters using CD2Cl2.
K.-W. Lin, C. Y. Chen, W.-F. Chen, T.-H. Yan, J. Org. Chem., 2008, 73, 4759-4761.

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.

An efficient and practical Cu-catalyzed asymmetric conjugate addition of dialkylzinc reagents to tetrasubstituted cyclic enones afforded quaternary all-carbon stereogenic centers in up to 95% ee. The products can be readily functionalized to afford various synthetically versatile compounds in high optical purity.
A. W. Hird, A. H. Hoveyda, J. Am. Chem. Soc., 2005, 127, 14988-14989.

The efficiency of the photoinduced radical addition of tertiary amines to olefinic double bonds is significantly enhanced and the stereoselectivity is influenced when thiocarbonyl compounds are added to the reaction mixture.
D. Harakat, J. Pesch, S. Marinkovic, N. Hoffmann, Org. Biomol. Chem., 2006, 4, 1202-1205.

Silyloxyallenes serve as highly useful α-acylvinyl anion equivalents, that undergo conjugate additions to alkylidene malonates in the presence of Sc(OTf)3 as catalyst. The reaction delivers intermolecular Rauhut-Currier products in excellent yields and regioselectivities for a wide scope of substrates.
T. E. Reynolds, M. S. Binkley, K. A. Scheidt, Org. Lett., 2008, 10, 2449-2452.

An efficient highly regio- and stereoselective iron-catalyzed conjugate addition of 2,3-allenoates with primary or secondary alkyl, phenyl, or vinyl Grignard reagents gives multi-substituted β,γ-unsaturated enoates in good yields. The in situ formed magnesium dienolate may readily react with different electrophilic reagents to construct an allylic quaternary carbon at the α-position of the ester group.
Z. Lu, G. Chai, S. Ma, J. Am. Chem. Soc., 2007, 129, 14546-14547.