Categories: C-H Bond Formation >
A Fukuzumi acridinium photooxidant with phenyldisulfide as a redox-active cocatalyst enable a direct, catalytic hydrodecarboxylation of primary, secondary, and tertiary carboxylic acids as well as a double decarboxylation of malonic acid derivatives. Substoichiometric quantities of Hünig’s base are used to reveal the carboxylate. Use of trifluoroethanol as a solvent allowed for significant improvements in substrate compatibilities.
J. D. Griffin, M. A. Zeller, D. A. Nicewicz, J. Am. Chem. Soc., 2015, 137, 11340-11348.
The Krapcho decarboxylation of alkyl malonate derivatives has been adapted to aqueous microwave conditions. For salt additives, a strong correlation was found between the pKa of the anion and the reaction rate, suggesting a straightforward base-catalyzed hydrolysis. Lithium sulfate gave the best results, obviating the need for DMSO as co-solvent.
J. D. Mason, S. S. Murphree, Synlett, 2013, 24, 1391-1394.
A base-catalyzed Michael-type addition of sodium diethyl malonate to N-Boc-α-amidoalkyl-p-tolyl sulfones in tetrahydrofuran followed by hydrolysis of the adducts in refluxing 6 M aqueous hydrochloric acid affords β3-amino acid hydrochlorides in high yield and excellent purity.
M. Nejman, A. Śliwińska, A. Zwierzak, Tetrahedron, 2005, 61, 8536-8541.
A mild decarboxylative reduction of naturally abundant carboxylic acids such as α-amino acids and α-hydroxy acids has been achieved via visible-light photoredox catalysis using an organocatalytic photoredox system. This method allows the synthesis of high-value compounds including medicinally relevant scaffolds and a monodecarboxylation of differently substituted dicarboxylic acids.
C. Cassani, G. Bergonzini, C.-J. Wallentin, Org. Lett., 2014, 16, 4228-4231.
An effective protocol allows the smooth protodecarboxylation of diversely functionalized aromatic carboxylic acids within 5-15 min under microwave irradiation. In the presence of an inexpensive catalyst generated in situ from copper(I) oxide and 1,10-phenanthroline, even nonactivated benzoates were converted in high yields.
L. J. Goossen, F. Manjolinho, B. A. Khan, N. Rodríguez, J. Org. Chem., 2009, 74, 2620-2623.
The combination of Pd(OAc)2/Et3SiH enables ligand-controlled non-decarbonylative and decarbonylative conversions of acyl fluorides. When tricyclohexylphosphine (PCy2) was used as the ligand, aldehydes were obtained as simple reductive conversion products, whereas 1,2-bis(dicyclohexylphosphino)ethane (Cy2P(CH2)2PCy2, DCPE) as the ligand favored the formation of hydrocarbons as decarbonylative reduction products.
Y. Ogiwara, Y. Sakuria, H. Hattori, N. Sakai, Org. Lett., 2018, 20, 4164-4167.
A simple and highly efficient protodecarboxylation of various heteroaromatic carboxylic acids is catalyzed by Ag2CO3 and AcOH in DMSO. This methodology enables also a selective monoprotodecarboxylation of several aromatic dicarboxylic acids.
P. Lu, C. Sanchez, J. Cornella, I. Larrosa, Org. Lett., 2009, 11, 5710-5713.
A copper-catalyzed aerobic oxidative decarboxylation of phenylacetic acids and α-hydroxyphenylacetic acids enables the synthesis of aromatic carbonyl compounds via decarboxylation, dioxygen activation, and C-H bond oxidation steps in a one-pot protocol with molecular oxygen as the sole terminal oxidant.
Q. Feng, Q. Song, J. Org. Chem., 2014, 79, 1867-1871.
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 use of FeCl3 as catalyst enables a rapid decarboxylation of methylene tethered cyclic 1,3-diesters in the presence of water to yield α,β-unsaturated acids with high E-stereoselectivity under both microwave and conventional heating conditions. This powerful approach proved to be scalable to gram scale synthesis.
A. R. Mohite, R. G. Bhat, Org. Lett., 2013, 15, 4564-4567.
A palladium-catalyzed chemoselective protodecarboxylation of polyenoic acids provides the desired polyenes in good yields under mild conditions using either a Pd(0) or Pd(II) catalyst. The reaction tolerates a variety of aryl and aliphatic substitutions.
M. H. Al-Huniti, M. A. Perez, M. K. Garr, M. P. Croatt, Org. Lett., 2018, 20, 7375-7379.
Diethyl N-Boc-iminomalonate, prepared on multi-gram scale, served as a stable and highly reactive electrophilic glycine equivalent which reacted with organomagnesium compounds affording substituted aryl N-Boc-aminomalonates. Subsequent hydrolysis produced arylglycines.
P. Cali, M. Begtrup, Synthesis, 2002, 63-64.
A practical one-step method for the preparation of α-chloroketones from readily available, inexpensive phenylacetic acid derivatives utilizes the unique reactivity of an intermediate Mg-enolate dianion, which displays selectivity for the carbonyl carbon of chloromethyl carbonyl electrophiles. Decarboxylation of the intermediate occurs spontaneously during the reaction quench.
M. J. Zacuto, R. F. Dunn, M. Figus, J. Org. Chem., 2014, 79, 8917-8925.
Enolizable carboxylic acids were converted in a single step to trifluoromethyl ketones. Treatment of the acid with LDA generated an enediolate that was trifluoroacetylated with EtO2CCF3. Quenching the reaction mixture with aqueous HCl resulted in rapid decarboxylation and provided the trifluoromethyl ketone product in good yield.
J. T. Reeves, J. J. Song, Z. Tan, H. Lee, N. K Yee, C. H. Senanayake, J. Org. Chem., 2008, 73, 9476-9478.
Malonic acid derivatives undergo unusually mild decarboxylation in the presence of N,N′-carbonyldiimidazole (CDI) at room temperature to generate a carbonyl imidazole intermediate in high yield. Subsequent reactions with various nucleophiles in an efficient one-pot process leads to amides, esters or carboxylic acids.
D. Lafrance, P. Bowles, K. Leeman, R. Rafka, Org. Lett., 2011, 13, 2322-2325.
A straightforward route allows the synthesis of 2-(hetero)arylated and 2,5-di(hetero)arylated oxazoles through regiocontrolled palladium-catalyzed direct (hetero)arylation of ethyl oxazole-4-carboxylate with iodo-, bromo-, and chloro(hetero)aromatics.
C. Verrier, T. Martin, C. Hoarau, F. Marsais, J. Org. Chem., 2008, 73, 7383-7386.
PPh3 catalyzes the iododecarboxylation of aliphatic carboxylic acid derived N-(acyloxy)phthalimide with lithium iodide as an iodine source under irradiation of 456 nm blue light-emitting diodes to provide primary, secondary, and bridgehead tertiary alkyl iodides.
M.-C. Fu, J.-X. Wang, R. Shang, Org. Lett., 2020, 22, 8572-8577.
A novel electrolytic system for non-Kolbe electrolysis based on the acid-base reaction between carboxylic acids and solid-supported bases in MeOH provide the corresponding methoxylated products in excellent yields. The acid-base reaction between carboxylic acids and solid-supported bases preferentially takes place to reduce the cell voltage in MeOH.
T. Tajima, H. Kurihara, T. Fuchigami, J. Am. Chem. Soc., 2007, 129, 6680-6681.
A cobalt-catalyzed decarboxylative methylation of primary and secondary aliphatic redox-active esters with trimethylaluminum provides methylated products without redox fluctuation under mild conditions. The use of triethylaluminum enables a decarboxylative ethylation.
Z.-Z. Wang, G.-Z. Wang, B. Zhao, R. Shang, Y. Fu, Synlett, 2020, 31, 1221-1225.
Using NaNO2 as the nitrogen source and Fe(OTf)3 as a promoter at 50°C, a series of arylacetic acids provides aromatic nitriles in good yields. The reaction is compatible with a broad range of functional groups.
Z. Shen, W. Liu, X. Tian, Z. Zhao, Y.-L. Ren, Synlett, 2020, 31, 1805-1808.
A catalytic decarboxylative halogenation of (hetero)aryl carboxylic acids accommodates an exceptionally broad scope of substrates. The generated aryl radical intermediate enables divergent functionalization pathways: (1) atom transfer to access bromo- or iodo(hetero)arenes or (2) radical capture by copper and subsequent reductive elimination to generate chloro- or fluoro(hetero)arenes.
T. Q. Chen, P. Scott Pedersen, N. W. Dow, R. Fayad, C. E. Hauke, M. S. Rosko, E. O. Danilov, D. C. Blakemore, A.-M. Dechert-Schmitt, T. Knauber, F. N. Castelano, D. W. C. MacMillan, J. Am. Chem. Soc., 2022, 144, 8296-8305.
A low-barrier photoinduced ligand to metal charge transfer (LMCT) enables a radical decarboxylative carbometalation strategy. Formation of a putative high-valent arylcopper(III) complex facilitates reductive eliminations to occur. This approach is suitable to address a previously unrealized general decarboxylative fluorination of benzoic acids at low temperature.
P. Xu, P. López-Rojas, T. Ritter, J. Am. Chem. Soc., 2021, 143, 5349-5354.
A highly enantioselective, general catalytic system for the facile synthesis of tertiary stereocenters adjacent to cyclic ketones relies on catalytic decarboxylative protonation of readily accessible racemic quaternary β-ketoesters.
J. T. Mohr, T. Nishimata, D. C. Behenna, B. M. Stoltz, J. Am. Chem. Soc., 2006, 128, 11348-11349.
Mild and selective heterobimetallic-catalyzed decarboxylative aldol reactions of allyl β-keto esters with aldehydes are promoted by Pd(0)- and Yb(III)-DIOP complexes at room temperature. The optimized reaction conditions require the addition of both metals.
S. Lou, J. A. Westbrook, S. E. Schaus, J. Am. Chem. Soc., 2004, 126, 11440-11441.
In the presence of as little as one mol-% of a Lewis acid catalyst, e.g. Mg(ClO4)2 or Cu(OTf)2, carboxylic acids can easily and near quantitatively be protected in a decarboxylative esterification at room temperature as methyl, benzyl, or t-butyl esters.
L. Goossen, A. Döhring, Adv. Synth. Catal., 2005, 345, 943-947.
A visible light-induced photocatalysis enables a general and practical decarboxylative hydroxylation of a broad range of carboxylic acids using molecular oxygen as the green oxidant. NaBH4 as additive reduces unstable peroxyl radical intermediates in situ.
S. N. Khan, M. K. Zaman, R. Li, Z. Sun, J. Org. Chem., 2020, 85, 5019-5026.
An efficient and practical approach to prepare phenols from benzoic acids using simple organic reagents at room temperature is compatible with various functional groups and heterocycles and can be easily scaled up. Mechanistic investigations suggest that the key migration step involves a free carbocation instead of a radical intermediate.
W. Xiong, Q. Shi, W. H. Liu, J. Am. Chem. Soc., 2022, 144, 15894-15902.
A photocatalytic direct decarboxylative hydroxylation of carboxylic acids enables the conversion of various readily available carboxylic acids to alcohols in good yields under extremely mild reaction conditions using molecular oxygen as a green oxidant and visible light as a driving force.
H.-T. Song, W. Ding, Q.-Q. Zhou, J. Liu, L.-Q. Lu, W.-J. Xiao, J. Org. Chem., 2016, 81, 7250-7255.
A hypervalent iodine reagent, (diacetoxyiodo)benzene, and catalytic amount of sodium azide in acetonitrile enable an oxidative decarboxylation of 2-aryl carboxylic acids into the corresponding aldehydes, ketones, and nitriles in good yields at room temperature. The advantages of this protocol are short reaction times and mild reaction conditions.
V. N. Telvekar, K. A. Sasane, Synlett, 2010, 2778-2779.