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Synthesis of 1,4-keto carboxylic acids, esters and amides


Recent Literature

Various oxo acid derivatives were obtained directly from the reaction of aliphatic and aromatic aldehydes with ω-alkenoic acid derivatives in the presence of rhodium(I) complexes and 2-amino-3-picoline.
E.-A. Jo, C.-H. Jun, Eur. J. Org. Chem., 2006, 2504-2507.

A photochemical process for the preparation of carboxylic acids from formate salts and alkenes proceeds in high yields across diverse functionalized alkene substrates with excellent regioselectivity. This operationally simple and redox-neutral hydrocarboxylation can be readily scaled in batch at low photocatalyst loading (0.01% photocatalyst).
S. N. Alektiar, Z. K. Wickens, J. Am. Chem. Soc., 2021, 143, 13022-13028.

Visible-light photoredox-catalyzed fragmentation of methyl N-phthalimidoyl oxalate allows direct construction of a 1,4-dicarbonyl structural motif by a regioselective conjugate addition of the methoxycarbonyl radical to reactive Michael acceptors.
Y. Slutskyy, L. E. Overman, Org. Lett., 2016, 18, 2564-2567.

An umpoled electrophilic 1,4-addition of CO2 to enones was achieved under photocatalytic conditions in the presence of an iridium photocatalyst and a benzimidazoline reductant under blue-light irradiation to give the corresponding γ-keto carboxylic acids. Aldehydes also coupled with enones to afford γ-keto alcohols (homoaldols) that were transformed into dihydrofurans and tetrahydrofurans.
S. Okumura, K. Torii, Y. Uozumi, Org. Lett., 2023, 25, 5226-5230.

A Rh/(S,S)-DTBM-YanPhos complex catalyzes an asymmetric anti-Markovnikov hydroformylation of α-substituted acrylates/acrylamides to provide a series of β-chiral linear aldehydes in high yields and enantioselectivities.
S. Li, Z. Li, C. You, X. Li, J. Yang, H. Lv, X. Zhang, Org. Lett., 2020, 22, 1108-1112.

Magnesium mediates a direct reductive carboxylation of easily prepared aryl vinyl ketones to provide γ-keto carboxylic acids in good yields under an atmosphere of carbon dioxide. The reaction offers eco-friendly reaction conditions, a short reaction time and wide substrate scope and provided a useful and convenient alternative to access biologically important γ-keto carboxylic acids.
S. Zheng, T. Zhang, H. Maekawa, J. Org. Chem., 2022, 87, 7343-7349.

A cationic rhodium(I)/dppb complex catalyzed direct intermolecular hydroacylation of N,N-dialkylacrylamides with both aliphatic and aromatic aldehydes represents a versatile route to γ-ketoamides in view of high atom economy and commercial availability of substrates.
K. Tanaka, Y. Shibata, T. Suda, Y. Hagiwara, M. Hirano, Org. Lett., 2007, 9, 1215-1218.

A cationic rhodium(I)/(R,R)-QuinoxP* complex catalyzes a highly enantioselective direct intermolecular hydroacylation of α-substituted acrylamides with unfunctionalized aliphatic aldehydes to yield the corresponding γ-ketoamides in high yields with excellent ee values.
Y. Shibata, K. Tanaka, J. Am. Chem. Soc., 2009, 131, 12552-12553.

Iridium photoredox catalysis enables a decarboxylative 1,4-addition of 2-oxo-2-(hetero)arylacetic acids to various Michael acceptors including α,β-unsaturated ester, ketone, amide, aldehyde, nitrile, and sulfone at room temperature. 2-Oxo-2-(hetero)arylacetic acids are easily accessible precursors of acyl anions through photoredox-catalyzed radical decarboxylation.
G.-Z. Wang, R. Shang, W.-M. Cheng, Y. Fu, Org. Lett., 2015, 17, 4830-4833.

Photoredox catalysis achieves a hydroacylation reaction of alkenes using readily available carboxylic acids as the acyl source and hydrosilanes as a hydrogen source. The protocol offers extremely mild conditions, broad substrate scope, and good functional group tolerance.
M. Zhang, R. Ruzi, J. Xi, N. Li, Z. Wu, W. Li, S. Yu, C. Zhu, Org. Lett., 2017, 19, 3430-3433.

Conjugated addition of primary nitroalkanes to α,β-unsaturated ketones or α,β-unsaturated esters, in the presence of two equivalents of DBU, allows the one-pot prepration of γ-diketones or γ-keto esters, respectively. The reaction of 2-aryl-1-nitroethane derivatives with α,β-unsaturated ketones gives cyclopentenones.
R. Ballini, L . Barboni, G. Bosica, D. Fiorini, Synthesis, 2002, 2725-2728.