Synthesis of Coumarins
Methods are reported for the efficient assembly of a series of phenol-derived propiolates and their Au(I)-catalyzed cyclization (intramolecular hydroarylation) to give the corresponding coumarins. Simple syntheses of natural products such as ayapin and scoparone have been realized.
A. Cervi, Y. Vio, C. L. L. Chai, M. G. Banwell, P. Lan, A. C. Willis, J. Org. Chem., 2021, 86, 178-198.
An efficient annulation of phenolic acetates with acrylates in the presence of [Rh2(OAc)4] as catalyst and formic acid as reducing agent provides high yield of coumarin derivatives via C-H bond activation. The addition of NaOAc as a base increased the yield of the products. The reaction is quite successful for both electron-rich as well as electron-deficient phenolic acetates, affording coumarins with excellent regioselectivity.
S. K. Gadakh, S. Dey, A. Sudalai, J. Org. Chem., 2015, 80, 11544-11550.
A benzannulation reaction of siloxy alkynes and salicylaldehydes efficiently provides a wide range of coumarins in the presence of NTf2 as catalyst. The polarized electron-rich triple bond might react sequentially with the aldehyde and hydroxy group by polarity switching in the stepwise formation of the C-C and C-O bonds.
H. Qian, J. Sun, Synlett, 2021, 32, 207-210.
The combination of palladium catalysis and iridium photocatalysis enables a general catalytic anti-hydroarylation of electron-deficient internal alkynes with a broad range of arylboronic acids. The reaction of ortho-substituted boronic acids provides pharmaceutically relevant heterocyclic cores via a cascade process.
J. Corpas, P. Mauleón, R. G. Arrayás, J. C. Carretero, Org. Lett., 2020, 22, 6473-6478.
Palladium-catalyzed oxidative Heck coupling reaction of coumarins and arylboronic acids allows a direct synthesis of 4-arylcoumarins in good yields. The reaction also showed tolerance toward functional groups such as hydro, methoxy, diethylamino, nitro, and chloro groups.
Y. Li, Z. Qi, H. Wang, X. Fu, C. Duan, J. Org. Chem., 2012, 77, 2053-2057.
The use of alkyl N-hydroxyphthalimide esters as alkylation reagents enables an efficient photocatalytic decarboxylative 3-position alkylation of coumarins in good yield. This protocol offers mild conditions, readily available starting materials, operational simplicity, and wide functional group tolerance.
C. Jin, Z. Yan, B. Sun, J. Yang, Org. Lett., 2019, 21, 2064-2068.
A facile iron-catalyzed decarboxylative radical coupling of alkyl diacyl peroxides with coumarins or chromones provides α-alkylated coumarins and β-alkylated chromones containing a wide scope of functional groups in good yields. The reaction proceeds smoothly without adding any ligand or additive and offers high regioselectivity, readily available starting materials, and operational simplicity.
C. Jin, X. Zhang, B. Sun, Z. Yan, T. Xu, Synlett, 2019, 30, 1585-1591.
Low loadings of inexpensive ZnBr2 catalyze a highly efficient synthesis of coumarins in very good yields from ynamides and salicylaldehydes. The sulfonamide moiety serves as an effective traceless directing group for high regioselectivity. The protocol offers good functional group tolerance, broad substrate scope, and recovery/reuse of the sulfonamides.
H. J. Yoo, S. W. Youn, Org. Lett., 2019, 21, 3422-3426.
The two discrete photochemical activation modes of (-)-riboflavin sequentially induce isomerization and cyclization by energy transfer (ET) and single-electron transfer (SET) activation pathways in an emulation of the coumarin biosynthesis pathway via a key photochemical E → Z isomerization step. The ensuing SET-based cyclization eliminates the need for a prefunctionalized aryl ring.
J. B. Metternich, R. Gilmour, J. Am. Chem. Soc., 2016, 138, 1040-1045.
A Ph3P/I2-Et3N-mediated one-pot two-step esterification-cyclization provides 3-aryl coumarins and 3-aryl-4-methylcoumarins from aryl acetic acids containing a steric or reactive group and 2-hydroxybenzaldehydes or 2′-hydroxyacetophenones smoothly at room temperature in good to excellent yields.
W. Phadhodee, C. Duangkamol, D. Yamano, M. Pattarawarapan, Synlett, 2017, 28, 825-830.
The employment of hydrophobic ionic liquids dramatically enhanced the activity of metal triflates in Friedel-Crafts alkenylations of aromatic compounds with various alkyl- and aryl-substituted alkynes.
C. E. Song, D.-U. Jung, S. Y. Choung, E. J. Roh, S.-G. Lee, Angew. Chem., 2004, 116, 6309-6311.
Visible-light-driven hydrocarboxylations as well as carbocarboxylations of alkynes using CO2 via an iridium/cobalt dual catalysis provide access to various pharmaceutically important heterocycles in a one-pot procedure from readily available alkynes. Coumarins, 2-quinolones, and 2-benzoxepinones were directly accessed through a one-pot alkyne hydrocarboxylation/alkene isomerization/cyclization sequence.
J. Hou, A. Ee, W. Feng, J.-H. Xu, Y. Zhao, J. Wu, J. Am. Chem. Soc., 2018, 140, 5257-5263.
Arylpropionic acid methyl esters having a MOM-protected hydroxy group at the ortho position underwent hydroarylation with various arylboronic acids in MeOH at ambient temperature in the presence of a catalytic amount of CuOAc, resulting in the formation of 4-arylcoumarins in high yields after the acidic workup.
Y. Yamamoto, N. Kirai, Org. Lett., 2008, 10, 5513-5516.
The use of cyanuric chloride (2,4,6-trichloro-1,3,5-triazine) and N-methyl morpholine enables an efficient and general protocol for a rapid synthesis of substituted 3-aryl coumarins. A series of substituted phenyl acetic acids have been successfully reacted with substituted 2-hydroxy benzaldehydes to afford 3-aryl coumarins in good to excellent yields.
K. V. Sashidhara, G. R. Palnati, S. R. Avula, A. Kumar, Synlett, 2012, 23, 611-621.
A direct carboxylation of alkenyl C-H bonds of 2-hydroxystyrenes in the presence of a catalytic amount of Pd(OAc)2 and Cs2CO3 as base under atmospheric pressure of CO2 afforded coumarins in good yield. The reaction undergoes a reversible nucleophilic addition of the alkenylpalladium intermediate to CO2.
K. Sasano, J. Takaya, N. Iwasawa, J. Am. Chem. Soc., 2013, 135, 10954-10957.
Palladium-catalyzed oxidative cyclocarbonylation of 2-vinylphenols enables a direct synthesis of various coumarins in good yields in the presence of low pressures of CO, and air or 1,4- benzoquinone as the oxidant. The reaction conditions are attractive in terms of environmental considerations and operational simplicity.
J. Ferguson, F. Zeng, H. Alper, Org. Lett., 2012, 14, 5602-5605.
Various aryl alkynoates and alkynanilides undergo fast intramolecular reaction at room temperature in the presence of a catalytic amount of Pd(OAc)2 and trifluoroacetic acid (TFA) as solvent to afford coumarins and quinolinones in good yields. The reaction tolerates a number of functional groups such as Br and CHO.
C. Jia, D. Piao, T. Kitamura, Y. Fujiwara, J. Org. Chem., 2000, 65, 7516-7522.
The reaction of in situ generated ortho-alkynyl quinone methides and a synthetic equivalent of acyl carbene provides a variety of alkynyl coumarins in very good yields. This versatile method enables also the preparation of β-alkenyl coumarins.
X. He, R. Li, P. Y. Choy, T. Liu, O. Y. Yuen, M. P. Leung, Y. Shang, F. Y. Kwong, Org. Lett., 2020, 22, 7348-7352.
Solvent-free conditions for the synthesis of coumarins via Pechmann and Knoevenagel condensation reactions offer waste minimization, simple operation and easier product work-up.
T. Sugino, K. Tanaka, Chem. Lett., 2001, 110-111.
The application of sonochemistry for the synthesis of different coumarins from active methylene compounds and 2-hydroxybenzaldehydes or resorcinol was very effective on a multigram scale with a higher yield, higher amount of crystalline compound, and shorter reaction time compared with the compounds obtained using the classical procedures.
L. S. da Silveira Pinto, M. V. N. de Souza, Synthesis, 2017, 49, 2555-2561.
The basic ionic liquid 1-butyl-3-methylimidazolium hydroxide, [bmIm]OH, efficiently catalyzes the Knoevenagel condensation of various aliphatic and aromatic aldehydes and ketones with active methylenes at room temperature without requirement of any organic solvent.
B. C. Ranu, R. Jana, Eur. J. Org. Chem., 2006, 3767-3770.
A facile, convenient, efficient, and high yielding synthesis of a combinatorial library of 3-aroylcoumarins has been developed by the condensation of easily available -aroylketene dithioacetals and 2-hydroxybenzaldehydes in the presence of catalytic amount of piperidine in THF reflux.
H. S. P. Rao, S. Sivakumar, J. Org. Chem., 2006, 71, 8715-8723.
The ionic liquid 1-butyl-3-methylimidazonium tetrafluoroborate [bmim]BF4 was used for ethylenediammonium diacetate (EDDA)-catalyzed Knoevenagel condensation between aldehydes or ketones with active methylene compounds. Catalyst and solvent can be recycled.
C. Su, Z.-C. Chen, Q.-G. Zhen, Synthesis, 2003, 555-559.
Upon activation with manganese powder, a cobalt-catalyzed C-H bond activation of coumarins with aryl halides or pseudohalides in the presence of carbon monoxide provides various 3-aroylcoumarin derivatives under mild conditions.
R. Pashazadeh, S. Rajai-Daryasarei, S. Mirzaei, M. Soheilizad, S. Ansari, M. Shabanian, Synthesis, 2019, 51, 3014-3020.
An efficient metal-free tandem acylation/cyclization of alkynoates with aldehydes enables the synthesis of 3-acyl-4-arylcoumarins via addition of acyl radical to alkynes and a C-H bond functionalization to form two new C-C bonds simultaneously.
X. Mi, C. Wang, M. Huang, Y. Wu, Y. Wu, J. Org. Chem., 2015, 80, 148-155.
Photocatalysis enables the construction of 3-acyl-4-arylcoumarins in good yields from simple aldehydes and ynoates in the presence of inexpensive 2-tBu-anthraquinone as catalyst. The reaction proceeds through generation of an acyl radical intermediate, that reacts with ynoate, and then cyclization.
K. Kawaai, T. Yamaguchi, E. Yamaguchi, S. Endo, N. Tada, A. Ikari, A. Itoh, J. Org. Chem., 2018, 83, 1988-1996.
4-Carboxyalkyl-8-formyl coumarins can be synthesized from 2-hydroxybenzaldehydes, triphenylphosphine and dialkyl acetylenedicarboxylate in good yields via vinyltriphenylphosphonium salt mediated aromatic electrophilic substitution.
K. C. Majumdar, I. Ansary, S. Samanta, B. Roy, Synlett, 2011, 694-698.
A new carbamoyl Baker-Venkataraman rearrangement allows a general synthesis of substituted 4-hydroxycoumarins in good overall yields. Intermediate arylketones are efficiently prepared via a Directed ortho Metalation - Negishi cross coupling protocol from arylcarbamates. The overall sequence provides a regiospecific anionic Friedel-Crafts complement for the construction of ortho-acyl phenols and coumarins.
A. V. Kalinin, A. J. M. Da Silva, C. C. Lopes, R. S. C. Lopes, V. Snieckus, Tetrahedron. Lett., 1998, 39, 4995-4998.
The use of Koser's reagent enables an efficient synthesis of 3-tosyloxy-4-hydroxycoumarins under mild conditions. The reaction tolerates various functional groups.
B. Xu, Y. Gao, J. Han, Z. Xing, S. Zhao, Z. Zhang, R. Ren, L. Wang, J. Org. Chem., 2019, 84, 10136-10144.
A chlorinative cyclization of aryl alkynoates in the presence of N-chlorosuccinimide (NCS) and Mes-Acr-MeClO4 as photocatalyst provides 3-chlorocoumarins under visible-light irradiation. The radical initiated reaction proceeds via Cl- addition, 5-exo-trig spirocyclization and subsequent 1,2-ester migration.
M. Pramanik, A. Mathuri, S. Sau, M. Das, P. Mal, Org. Lett., 2021, 23, 8088-8092.
An exclusive 6-endo-dig iodocyclization of 3-ethoxy-1-(2-alkoxyphenyl)-2-yn-1-ols gives 4-substituted 3-iodocoumarins, whereas a 5-endo-dig iodocyclization of 1-alkoxy-4-ethoxy-3-yn-1,2-diols gives 3-iodobutenolides respectively. The reactions are carried out under very mild conditions using I2 in DCM or toluene at room temperature.
M. S. Reddy, N. Thirupathi, M. H. Babu, S. Puri, J. Org. Chem., 2013, 78, 5878-5888.
C3-N-substituted coumarins can be synthesized in good yields directly from coumarins and azides in the presence of Pr(OTf)3 without additives or ligands.
J.-l. Li, D.-c. Hu, X.-p. Liang, Y.-C. Wang, H.-S. Wang, Y.-m. Pan, J. Org. Chem., 2017, 82, 9006-9001.
The use of CF3SO2Cl as the trifluoromethyl radical source enables a highly efficient synthesis of 3-trifluoromethyl coumarins in very good yields from ester 3-arylpropiolates under visible light irradiation. The reaction incorporates a cascade cyclization/dearomatization/ester migration/oxidization/rearomatization process.
L. Chen. L. Wu, W. Duan, T. Wang, L. Li, K. Zhang, J. Zhu, Z. Peng, F. Xiong, J. Org. Chem., 2018, 83, 8607-8614.