Categories: C-S Bond Formation >
Synthesis of thioesters and thioacids
An efficient, fast and convenient protocol for the synthesis of N-urethane-protected α-amino/peptide thioacids from their corresponding acids and Na2S is mediated by EDC. The chemistry is compatible with a wide variety of urethane protecting groups, side-chain functionalities, and sterically hindered amino acids.
T. M. Vishwanatha, M. Samarasimhareddy, V. V. Sureshbabu, Synlett, 2012, 23, 89-92.
A thiazolium precatalyst facilitates electrochemical oxidation of thiolate anions, leading to deleterious formation of disulfide byproducts. For the reaction of a broad range of aldehyde and thiol substrates, thioesters were obtained in very good yields . This approach provides an atom-efficient thioesterification that circumvents the need for stoichiometric exogenous oxidants, high cell potentials, or redox mediators.
K. A. Ogawa, A. J. Boydston, Org. Lett., 2014, 16, 1928-1931.
4,4′-azopyridine is a suitable electron-deficient reagent for Mitsunobu esterification and thioesterification reactions. This new reagent facilitates the isolation of its hydrazine byproduct without restricting the reaction scope. The pyridine hydrazine byproduct can be simply reoxidized. The stereochemistry of the reaction under the reported conditions is with perfect retention of configuration.
N. Iranpoor, H. Firouzabadi, D. Khalili, S. Motevalli, J. Org. Chem., 2008, 73, 4882-4887.
Reduction of ethanethiol esters of α-amino acids to α-amino aldehydes by triethylsilane and catalytic palladium-on-carbon is described. α-Amino aldehydes with Boc, Cbz, or Fmoc protection could be obtained without racemization in high yield.
H. Tokuyama, S. Yokoshima, S.-C. Lin, L. Li, T. Fukuyama, Synthesis, 2002, 1121-1123.
The photocatalytic activation of elemental sulfur enables a mild, rapid, and chemoselective three-component thioesterification in the presence of olefins and α-ketoacids. This novel reaction is characterized by high yields and a broad substrate scope.
S. Murakami, T. Nanjo, Y. Takemoto, Org. Lett., 2021, 23, 7650-7655.
Diverse thiol esters were synthesized in good yields by reactions of thiophenol, benzyl mercaptan, ethyl mercaptoacetate, and mercaptoacetic acid with N-acylbenzotriazoles under mild conditions. These results demonstrate the utility of N-acylbenzotriazoles as mild S-acylating agents.
A. R. Katritzky, A. A. Shestopalov, K. Suzuki, Synthesis, 2004, 1806-1813.
The addition of 3-10 mol-% DMAP accelerates the DCC-activated esterification of carboxylic acids with alcohols and thiols to such an extent that formation of side products is suppressed and even sterically demanding esters are formed in good yields at room temperature.
B. Neises, W. Steglich, Angew. Chem. Int. Ed., 1978, 17, 522-524.
A convenient procedure allows the synthesis of esters and thioesters from the corresponding carboxylic acid using TFFH as the coupling reagent. The preparation of N-acyl-dithiocarbamates from carboxylic acids and 1,3-thiazolidine-2-thione is also described.
M. Pittelkow, F. S. Kamounah, U. Boas, B. Pedersen, J. B. Christensen, Synthesis, 2004, 2485-2492.
A copper-catalyzed oxidative coupling of readily available aroylhydrazides with disulfides enables an alternative thioesterification reaction, in which oxidative expulsion of N2 overcomes the activation barrier between the carboxylic acid derivatives and the products. The reaction produces various thioesters in good to excellent yields with good functional group tolerance.
S. Xie, L. Su, M. Mo, W. Zhou, Y. Zhou, J. Dong, J. Org. Chem., 2021, 86, 739-749.
A nickel-catalyzed thiocarbonylation of arylboronic acid with sulfonyl chlorides in the presence of Mo(CO)6 as CO source and reductant provides a broad range of thioesters in good yields with good functional group tolerance.
X. Qi, Z.-P. Bao, X.-T. Yao, X.-F. Wu, Org. Lett., 2020, 22, 6671-6676.
The facile and efficient conversion of a tert-butyl protecting group to an acetyl protecting group by catalytic amounts of bromine in acetyl chloride and the presence of acetic acid has been developed. The fairly mild reaction conditions are of particular interest for new protecting group strategies for sulfur functionalised target structures.
A. Blaszczyk, M. Elbing, M. Mayor, Org. Biomol. Chem., 2004, 2, 2722-2724.
Various alcohols, thiols, phenols, and amines can be acetylated using acetic anhydride in the presence of catalytic quantity of silver triflate. The method proceeds under mild conditions, does not involve cumbersome workup, and the resulting products are obtained in high yields within a reasonable time.
R. Das, D. Chakraborty, Synthesis, 2011, 1621-1625.
Various alcohols, phenols, amines and thiols may easily be converted into acetate derivatives by treatment with acetic anhydride in the presence of acetonyltriphenylphosphonium bromide in good yields at room temperature. With the same precatalyst, both aliphatic and aromatic aldehydes can be transformed into the corresponding gem-diacetates under reflux conditions.
A. T. Khan, L. H. Choudry, S. Ghosh, Eur. J. Org. Chem., 2005, 2782-2787.
Copper(II) tetrafluoroborate efficiently catalyzes acetylation of structurally diverse phenols, alcohols, thiols, and amines with stoichiometric amounts of Ac2O under solvent-free conditions at room temperature. Acid-sensitive alcohols are smoothly acetylated without competitive side reactions.
A. K. Chakraborti, R. Gulhane, Shivani, Synthesis, 2004, 111-115.
An atom efficient esterification could be achieved using hafnium(IV) or zirconium(IV) salts.
K. Ishihara, M. Nakayama, S. Ohara, H. Yamamoto, Tetrahedron, 2002, 58, 8179-8188.
Acylation of alcohols, thiols, and sugars were studied with a variety of Lewis acids, and it was found that Cu(OTf)2 was very efficient in catalyzing the reaction under mild conditions in CH2Cl2.
K. L. Chandra, P. Saravan, R. K. Singh, V. K. Singh, Tetrahedron, 2002, 58, 1369-1374.
Ground-state destabilization of amides enables an exceedingly mild method for the direct thioesterification and selenoesterification by selective N-C(O) bond cleavage in the absence of transition metals. Acyclic amides undergo N-C(O) to S/Se-C(O) interconversion to give the corresponding thioesters and selenoesters in excellent yields at room temperature via a tetrahedral intermediate pathway.
Md. M. Rahman, G. Li, M. Szostak, Synthesis, 2020, 52, 1060-1066.
A palladium-catalyzed desulfonative carbonylation of S-aryl/alkyl benzenesulfonothioates provides thioesters in good yields by SO2 extrusion and CO insertion under 1 bar of CO. Dimethylacetamide (DMAc) as solvent facilitated this desulfonative carbonylation due to its high absorbing ability of SO2.
J.-X. Xu, L.-C. Wang, X.-F. Wu, Org. Lett., 2022, 24, 4820-4824.
The thiocarbonylation of gem-difluoroalkenes with thiols provides acyethanethioates in good yields in the presence of water under mild conditions without the use of any additives.
X. Jiang, G. Wang, Z. Zheng, X. Yu, Y. Hong, H. Xia, C. Yu, Org. Lett., 2020, 22, 9762-9766.
The combination of thiols as nucleophiles and a bidentate ligand enable a palladium-catalyzed thiocarbonylation of styrene derivatives with high regioselectivity toward the more valuable branched isomer. The ambient reaction conditions (temperature, catalyst loading) and the use of a CO surrogate render this transformation a useful method for the synthesis of thioesters.
V. Hirschbeck, P. H. Gehrtz, I. Fleischer, J. Am. Chem. Soc., 2016, 138, 16794-16799.
A direct Csp3-H bond oxidative thioesterification of methyl ketones with aromatic thiols/disulfides is promoted by TBAI/K2S2O8 to provide functionalized α-ketothioesters. This efficient reaction offers large-scale applicability and broad functional group tolerance.
B. Hu, Pan Zhou, Q. Zhang, Y. Wang, S. Zhao, L. Lu, S. Yan, F. Yu, J. Org. Chem., 2018, 83, 14978-14986.
A Pd-catalyzed hydrothiocarbonylation of unactivated terminal alkenes provides aliphatic thioesters with exclusive linear selectivity under mild reaction conditions in very good yields, broad substrate scope, and broad functional group tolerance.
W. Yu, J. Han, D. Fang, M. Wang, J. Liao, Org. Lett., 2021, 23, 2482-2487.
Oxalic acid monothioesters (OAM) can be used as a thioester synthetic equivalent for palladium-catalyzed decarboxylative thiocarbonylation of organohalides and hydrothiocarbonylation of unsaturated carbon-carbon bonds at room temperature with high chemo- and regioselectivity.
B. Zhao, Y. Fu, R. Shang, Org. Lett., 2019, 21, 9521-9526.
A nickel-catalyzed reductive coupling of aryl triflates with O-tBu S-alkyl thiocarbonates provides thioesters in good yields via a chemoselective cleavage of the C-O bond of the thiocarbonate. This work broadens the scope of nickel-catalyzed reductive cross-electrophile coupling reactions.
Z. Zhu, Y. Gong, W. Tong, W. Xue, H. Gong, Org. Lett., 2021, 23, 2158-2163.
Simple thioesters undergo direct aldol addition to aldehydes in the presence of a Lewis acid and i-Pr2NEt. The reactions proceed extremely rapidly and in excellent yield.
J. M. Yost, G. Zhou, D. M. Coltart, Org. Lett., 2006, 8, 1503-1506.
Mild and Efficient Pentafluorophenylammonium Triflate (PFPAT)-Catalyzed C-Acylations of Enol Silyl Ethers or Ketene Silyl (Thio)Acetals with Acid Chlorides
A. Iida, J. Osada, R. Nagase, T. Misaki, Y. Tanabe, Org. Lett., 2007, 9, 1859-1862.
A Ti-crossed Claisen condensation between ketene silyl (thio)acetals and acid chlorides gave α-monoalkylated (thio)esters and thermodynamically unfavorable α,α-dialkylated β-keto (thio)esters in good yield. The protocol was extended to the direct condensation of ketene silyl acetals with carboxylic acids.
A. Iida, S. Nakazawa, T. Okabayashi, A. Horii, T. Misako, Y. Tanabe, Org. Lett., 2006, 8, 5215-5218.