Recent Advances in Palladium-Catalyzed Asymmetric Hydroesterification of Alkenes

doi:10.6023/cjoc202509035

Abstract

Asymmetric hydroesterification has become one of the most attractive pathways for synthesizing chiral carboxylic acid derivatives due to its atom economy and step simplicity. The core challenge of this reaction lies in the simultaneous achievement of synergistic control over high chemo-, regio-, and enantioselectivity. Chiral ligands, as key components of the catalytic system, directly govern the catalytic efficiency and stereochemical control of the reaction by precisely modulating the stereoelectronic properties and coordination environment of the transition metal active center. This review systematically summarizes the research progress over decades in palladium-catalyzed asymmetric hydroesterification of alkenes, critically evaluates the breakthrough contributions of innovative chiral ligand design to selectivity control, and discusses the challenges and future development directions in this field.

Key words: chiral ligands, asymmetric, hydroesterification, palladium-catalyzed

Cite this article

Kai Feng, Zhaobo He, Zhen Wang. Recent Advances in Palladium-Catalyzed Asymmetric Hydroesterification of Alkenes[J]. Chinese Journal of Organic Chemistry, 2026, 46(5): 1897-1915.

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Fig. & Tab. 28

Figure 1. Asymmetric hydroesterification reactions

Figure 2. Research progress on asymmetric hydroesterification of styrene

Figure 3. Application of chiral catalysts in asymmetric hydroesterification reactions

Figure 4. Synthesis of 2-arylpropionic acid phenyl ester using phenyl formate as carbonyl source

Figure 5. Asymmetric hydroesterification of α-aryl acrylic acid

Figure 6. Asymmetric hydroesterification of intracyclic alkenes

Figure 7. β-Carbonyl-assisted asymmetric hydroesterification of alkenes

Figure 8. Thiol-involved asymmetric hydroesterification of conjugated dienes

Figure 9. Thiol-involved asymmetric hydroesterification of aryl olefins

Figure 10. Asymmetric hydroesterification involving tert-butyl mercaptan

Figure 11. Hydroesterification of allylic alcohols

Figure 12. Asymmetric hydroesterification of polysubstituted allylic alcohols with (－)-BPPM

Figure 13. Asymmetric hydroesterification of polysubstituted allylic alcohols with BICP

Figure 14. Synthesis of chiral THF-fused bicyclic γ-lactone

Figure 15. Control experiments

Figure 16. Asymmetric hydroesterification of allylic alcohols with (S,S)-DIOP

Figure 17. Asymmetric hydroesterification of alkenylphenols with phenyl formate

Figure 18. Mechanism of asymmetric hydroesterification between alkenylphenols and phenyl formate

Figure 19. Asymmetric hydroesterification between alkenylphenols and (R,R,R,R)-WingPhos

Figure 20. Asymmetric hydroesterification reaction of tertiary alcohols

Figure 21. Asymmetric hydrocarboxylation catalyzed by PdCl2/CuCl2

Figure 22. Asymmetric hydrocarboxylation catalyzed by water-soluble palladium complexes

Figure 23. Application of chiral catalysts in asymmetric hydrocarboxylation

Figure 24. Asymmetric hydrocarboxylation reaction involving chiral spirocyclic ligand

Figure 25. Asymmetric hydrocarboxylation reaction for the synthesis of chiral drug molecules.

Figure 26. Asymmetric hydrocarboxylation of cyclic olefins

Figure 27. Auxiliary group-promoted asymmetric hydrocarboxylation

Figure 28. Palladium relay-catalyzed asymmetric double hydro-carbonylation of alkynes

References 56

[1]	(a) Moen M. D.; Keam S. J. CNS Drugs 2009, 23, 1057. doi: 10.2165/11201140-000000000-00000
	(b) Butler A. R.; Wu Y.-L. Chem. Soc. Rev. 1992, 21, 85. doi: 10.1039/cs9922100085
	(c) Xia J. Y.; Yang D. Q.; Long Y. H. Chin. J. Org. Chem. 2011, 31, 593 (in Chinese).
	(夏九云, 杨定乔, 龙玉华, 有机化学, 2011, 31, 593.)
	(d) Wang J. G.; Xu C. C.; Wong Y. K.; Li Y. J.; Liao F. L.; Jiang T. L.; Tu Y. Y. Engineering 2019, 5, 32.
	(e) Halama A.; Zapadlo M. Org. Process Res. Dev. 2019, 23, 102. doi: 10.1021/acs.oprd.8b00350
	(f) Ma K. Q.; Martin B. S.; Yin X. L.; Dai M. J. Nat. Prod. Rep. 2019, 36, 174. doi: 10.1039/C8NP00033F
	(g) Iacoviello M.; Palazzuoli A.; Gronda E. Eur. J. Clin. Invest. 2021, 51, e13624. doi: 10.1111/eci.v51.11
	(h) Li J. H.; Shi Y. A. Chem. Soc. Rev. 2022, 51, 6757. doi: 10.1039/D2CS00150K
	(i) Kuai C.-S.; Wang Y. R.; Yang T.; Wu X.-F. J. Am. Chem. Soc. 2025, 147, 7950. doi: 10.1021/jacs.5c00032
[2]	(a) Yang H.; Tang W. J. Chem. Rec. 2020, 20, 23. doi: 10.1002/tcr.v20.1
	(b) Mas-Roselló J.; Herraiz A. G.; Audic B.; Laverny A.; Cramer N. Angew. Chem. Int. Ed. 2021, 60, 13198. doi: 10.1002/anie.v60.24
	(c) Margalef J.; Biosca M.; de la Cruz Sánchez P.; Faiges J.; Pàmies O.; Diéguez M. Coord. Chem. Rev. 2021, 446, 214120. doi: 10.1016/j.ccr.2021.214120
	(d) Wang H.; Wen J. L.; Zhang X. M. Chem. Rev. 2021, 121, 7530. doi: 10.1021/acs.chemrev.1c00075
[3]	(a) Knowles W. S.; Sabacky M. J. J. Chem. Soc., Chem. Commun. 1968, 20, 1445.
	(b) Horner L.; Sieged H.; Buthe H. Angew. Chem. Int. Ed. 1968, 7, 942.
	(c) Ni H. Z.; Chan W.-L.; Lu Y. X. Chem. Rev. 2018, 118, 9344. doi: 10.1021/acs.chemrev.8b00261
	(d) Xu G. Q.; Senanayake C. H.; Tang W. J. Acc. Chem. Res. 2019, 52, 1101. doi: 10.1021/acs.accounts.9b00029
	(e) Imamoto T. Proc. Jpn. Acad., Ser. B 2021, 97, 520. doi: 10.2183/pjab.97.026
	(f) Stephan M.; Jeran M.; Mohar B. Org. Process Res. Dev. 2024, 28, 11. doi: 10.1021/acs.oprd.3c00333
	(g) Chen W.; Cai P.; Zhou H. C.; Madrahimov S. T. Angew. Chem. Int. Ed. 2024, 63, e202315075. doi: 10.1002/anie.v63.12
	(h) Su L.; Gao S.; Liu J. W. Nat. Commun. 2024, 15, 7248. doi: 10.1038/s41467-024-51717-8
	(i) Ye B. H.; Su L.; Zheng K. T.; Gao S.; Liu J. W. Angew. Chem. Int. Ed. 2025, 64, e202413949.
[4]	(a) Zhou Y. R.; Gong Y. F. Eur. J. Org. Chem. 2011, 6092.
	(b) Shen X. Z.; Chen X.; Chen J. P.; Sun Y. F.; Cheng Z. Y.; Lu Z. Nat. Commun. 2020, 11, 783. doi: 10.1038/s41467-020-14459-x
	(c) Liu W.; Jiang Q. W.; Yang X. Y. Angew. Chem. Int. Ed. 2020, 59, 23598. doi: 10.1002/anie.v59.52
	(d) Wu X. Q.; Turlik A. T.; Luan B. X.; He F.; Qu J. P.; Houk K. N.; Chen Y. F. Angew. Chem. Int. Ed. 2022, 61, e202207536. doi: 10.1002/anie.v61.36
	(e) Wu X. Q.; Qu J. P.; Chen Y. F. J. Am. Chem. Soc. 2020, 142, 15654. doi: 10.1021/jacs.0c07126
	(f) Wu X. Q.; Li H. Y.; He F.; Qu J. P.; Chen Y. F. Chin. J. Chem. 2023, 41, 1673. doi: 10.1002/cjoc.v41.14
	(g) Jin L.; Li Y.; Mao Y. H.; He X.-B.; Lu Z.; Zhang Q.; Shi B.-F. Nat. Commun. 2024, 15, 4908. doi: 10.1038/s41467-024-48582-w
	(h) Cui B.; Zheng Y. T.; Sun H.; Shang H. J.; Du M.; Shang Y. X.; Yavuz C. T. Nat. Commun. 2024, 15, 6647. doi: 10.1038/s41467-024-50757-4
[5]	(a) Hiroi K.; Sone T. Curr. Org. Synth. 2008, 5, 305. doi: 10.2174/157017908786241608
	(b) Liu Z. Q.; Feng X. Q.; Du H. F. Org. Lett. 2012, 14, 3154. doi: 10.1021/ol301248d
	(c) Trost B. M.; Rao M. Angew. Chem. Int. Ed. 2015, 54, 5026. doi: 10.1002/anie.v54.17
	(d) Otocka S.; Kwiatkowska M.; Madalinska L.; Kiełbasiński P. Chem. Rev. 2017, 117, 4147. doi: 10.1021/acs.chemrev.6b00517
	(e) Li X.; Zheng S.-C.; Zhao X.-M. Eur. J. Org. Chem. 2025, 28, e202401172. doi: 10.1002/ejoc.v28.5
[6]	(a) Su B.; Zhou T.-G.; Xu P.-L.; Shi Z.-J.; Hartwig J. F. Angew. Chem. Int. Ed. 2017, 56,7205. pmid: 40711534
	(b) Babu K. N.; Kinthada L. K.; Das P. P.; Bisai A. Chem. Commun. 2018, 54, 7963. doi: 10.1039/C8CC04338H pmid: 40711534
	(c) Zhang S. T.; Wu S. J.; Wang Q.; Xu S. J.; Han Y.; Yan C.-G.; Zhang J. L.; Wang L. Angew. Chem. Int. Ed. 2023, 62, e202300309. doi: 10.1002/anie.v62.20 pmid: 40711534
	(d) Tu Y. S.; Xu B.; Wang Q.; Dong H. L.; Zhang Z.-M.; Zhang J. L. J. Am. Chem. Soc. 2023, 145, 4378. doi: 10.1021/jacs.2c12752 pmid: 40711534
	(e) Liao G.; Shi B.-F. Acc. Chem. Res. 2025, 58, 1562. doi: 10.1021/acs.accounts.5c00173 pmid: 40711534
	(f) Yan X.; Feng W.; Ng J. X.; Li J. X.; Liu Y.; Zhang B.; Shao P.-L.; Zhao Y. Chem. Soc. Rev. 2025, 54, 7966. doi: 10.1039/d4cs00966e pmid: 40711534
[7]	(a) Lin G.-Q.; Li Y.-M.; Chan A. S. C. Principles and Applications of Asymmetric Synthesis, Wiley, New York, 2001.
	(b) Xie J.-H.; Zhou Q.-L. Acta Chim. Sinica 2012, 70, 1427 (in Chinese). doi: 10.6023/A12060268
	(谢建华, 周其林, 化学学报, 2012, 70, 1427.) doi: 10.6023/A12060268
	(c) Zhao W. X.; Yang D. Y.; Zhang Y. H. Chin. J. Org. Chem. 2016, 36, 2301 (in Chinese). doi: 10.6023/cjoc201603006
	(赵文献, 杨代月, 张玉华, 有机化学, 2016, 36, 2301.) doi: 10.6023/cjoc201603006
[8]	(a) Yu X. H.; Wang W. Chem. Asian J. 2008, 3, 516. doi: 10.1002/asia.v3:3 pmid: 18506834
	(b) Lyubimov S. E.; Kalinin V. N.; Tyutyunov A. A.; Olshevskaya V. A.; Dutikova Y. V.; Cheong C. S.; Petrovskii P. V.; Safronov A. S.; Davankov V. A. Chirality 2009, 21, 2. doi: 10.1002/chir.20565 pmid: 18506834
	(c) Luo J.; Zhang T.; Wang L.; Liao G.; Yao Q. J.; Wu Y. J.; Zhan B. B.; Lan Y.; Lin X. F.; Shi B. F. Angew. Chem. Int. Ed. 2019, 58, 6708. doi: 10.1002/anie.v58.20 pmid: 18506834
	(d) Liu X.-R.; Cui P.-F.; Guo S.-T.; Lin Y.-J.; Jin G.-X. J. Am. Chem. Soc. 2021, 143, 5099. doi: 10.1021/jacs.1c00779 pmid: 18506834
	(e) Li P. P.; Zheng E.; Li G. L.; Luo Y. C.; Huo X. H.; Ma S. M.; Zhang W. B. Science 2024, 385, 972. doi: 10.1126/science.ado4936 pmid: 18506834
[9]	(a) Ren X. Y.; Wang Z.; Shen C. R.; Tian X. X.; Tang L.; Ji X. L.; Dong K. W. Angew. Chem. Int. Ed. 2021, 60,17693.
	(b) Wang Z.; Shen C. R.; Dong K. W. Angew. Chem. Int. Ed. 2024, e202410967.
	(c) Wang Z.; Dong K. W. Chin. J. Org. Chem. 2024, 44, 3249 (in Chinese). doi: 10.6023/cjoc202402003
	(王震, 董开武, 有机化学, 2024, 44, 3249). doi: 10.6023/cjoc202402003
[10]	(a) Clegg W.; Elsegood M. R. J.; Eastham G. R.; Tooze R. P.; Wang X. L.; Whiston K. Chem. Commun. 1999, 1877. pmid: 11840990
	(b) Kiss G. Chem. Rev. 2001, 101, 3435. pmid: 11840990
	(c) del Río I.; Ruiz N.; Claver C. Inorg. Chem. Commun. 2000, 3, 166. pmid: 11840990
	(d) Godard C.; Muñoz B. K.; Ruiz A.; Claver C. Dalton Trans. 2008, 853. pmid: 11840990
[11]	(a) Xu Z. S.; Shen C. R.; Zhang H. R.; Wang P.; Dong K. W. Org. Chem. Front. 2021, 8, 1163. doi: 10.1039/D0QO01486A
	(b) Peng J.-B.; Liu X.-L.; Li L.; Wu X.-F. Sci. China: Chem. 2022, 65, 441.
	(c) Cheng S. D.; Luo Y.; Yu T.; Li J.; Gan C. F.; Luo S.; Zhu Q. ACS Catal. 2022, 12, 837. doi: 10.1021/acscatal.1c05319
	(d) Shen C. R.; Dong K. W. Synlett 2022, 33, 815. doi: 10.1055/a-1796-2255
[12]	(a) Botteghi C.; Consiglio G.; Pino P. Chimia 1973, 27, 477. doi: 10.2533/chimia.1973.477
	(b) Consiglio G.; Pino P. Chimia 1976, 30, 193. doi: 10.2533/chimia.1976.193
	(c) Consiglio G. Helv. Chim. Acta 1976, 59, 124. doi: 10.1002/hlca.v59:1
	(d) Consiglio G. J. Organomet. Chem. 1977, 132, C26.
[13]	Hayashi T.; Tanaka M.; Ogata I. Tetrahedron Lett. 1978, 41, 3925. doi: 10.1016/S0040-4020(01)97174-1
[14]	Cometti G.; Chiusoli G. P. J. Organomet. Chem. 1982, 236, C31.
[15]	Zhou H. Y.; Hou J. G.; Cheng J.; Lu S. J.; Fu H. X.; Wang H. Q. J. Organomet. Chem. 1997, 543, 227. doi: 10.1016/S0022-328X(97)00241-6
[16]	Oi S.; Nomura M.; Aiko T.; Inoue Y. J. Mol. Catal. A: Chem. 1997, 115, 289. doi: 10.1016/S1381-1169(96)00282-8
[17]	Beller M.; Comils B.; Frohning C. D.; Kohlpaintner C. W. J. Mol. Catal. A: Chem. 1995, 104, 17. doi: 10.1016/1381-1169(95)00130-1
[18]	Nozaki K.; Kantam M. L.; Horiuchi T.; Takaya H. J. Mol. Catal. A: Chem. 1997, 118, 247. doi: 10.1016/S1381-1169(96)00385-8
[19]	Wang L. L.; Kwok W. H.; Chan A. S.; Tu T.; Hou X. L; Dai L. X. Tetrahedron: Asymmetry 2003, 14, 2291.
[20]	Kawashima Y.; Okano K.; Nozaki K.; Hiyama T. Bull. Chem. Soc. Jpn. 2004, 77, 347. doi: 10.1246/bcsj.77.347
[21]	Muñoz B. K.; Marinetti A.; Ruiz A.; Castillon S.; Claver C. Inorg. Chem. Commun. 2005, 8, 1113. doi: 10.1016/j.inoche.2005.09.006
[22]	Marinetti A.; Kruger V.; Buzin F.-X. Coord. Chem. Rev. 1998, 178-180, 755. doi: 10.1016/S0010-8545(98)00149-0
[23]	Muñoz B. K.; Godard C.; Marinetti A.; Ruiz A.; Benet-Buchholz J.; Claver C. Dalton Trans. 2007, 47, 5524.
[24]	Godard C.; Ruiz A.; Claver C. Helv. Chim. Acta 2006, 89, 1610. doi: 10.1002/hlca.v89:8
[25]	Guiu E.; Caporali M.; Munoz B.; Müller C.; Lutz M.; Spek A. L.; van Leeuwen P. W. Organometallics 2006, 25, 3102. doi: 10.1021/om060121t
[26]	Yao Y.-H.; Zou X.-J.; Wang Y.; Yang H.-Y.; Ren Z.-H; Guan Z.-H. Angew. Chem. Int. Ed. 2021, 60, 23117. doi: 10.1002/anie.202107856 pmid: 34240535
[27]	Chelucci G.; Cabras M. A.; Botteghi C.; Chelucci M. Tetrahedron: Asymmetry 1994, 5, 299.
[28]	Konrad T. M.; Fuentes J. A.; Slawin A. M. Z.; Clarke M. L. Angew. Chem. Int. Ed. 2010, 49, 9197. doi: 10.1002/anie.201004415 pmid: 20979073
[29]	Konrad T. M.; Durrani J. T.; Cobley C. J.; Clarke M. L. Chem. Commun. 2013, 49, 3306. doi: 10.1039/c3cc41291a
[30]	Gallarati S.; Dingwall P.; Fuentes J. A.; Bühl M.; Clarke M. L. Organometallics 2020, 39, 4544. doi: 10.1021/acs.organomet.0c00613
[31]	Harkness G. J.; Clarke M. L. Eur. J. Org. Chem. 2017, 4859.
[32]	Li J. F.; Chang W. J.; Ren W. L.; Dai J.; Shi Y. A. Org. Lett. 2016, 18, 5456. doi: 10.1021/acs.orglett.6b02467
[33]	Li J. F.; Ren W. L.; Dai J.; Shi Y. A. Org. Chem. Front. 2018, 5, 75. doi: 10.1039/C7QO00622E
[34]	Pongrácz P.; Seni A. A.; Mika L. T.; Kollár L. Mol. Catal. 2017, 438, 15.
[35]	Ji X. L.; Shen C. R.; Tian X. X.; Dong K. W. Org. Lett. 2021, 23, 8645. doi: 10.1021/acs.orglett.1c03361
[36]	Zhou H. Y.; Lu S. J.; Hou J. G.; Chen J.; Fu H. X.; Wang H. Q. Chem. Lett. 1996, 339.
[37]	Blanco C.; Ruiz A.; Godard C.; Fleury-Bregeot N.; Marinetti A.; Claver C. Adv. Synth. Catal. 2009, 351, 1813. doi: 10.1002/adsc.v351:11/12
[38]	Andrieu J.; Braunstein P.; Naud F.; Adams R. D. J. Organomet. Chem. 2000, 601, 43. doi: 10.1016/S0022-328X(00)00019-X
[39]	Fuentes J. A.; Durrani J. T.; Leckie S. M.; Crawford L.; Bühl M.; Clarke M. L. Catal. Sci. Technol. 2016, 6, 7477. doi: 10.1039/C6CY01268J
[40]	(a) Castarlenas R.; Di Giuseppe A.; Pérez-Torrente J. J.; Oro L. A. Angew. Chem. Int. Ed. 2013, 52, 211. doi: 10.1002/anie.201205468 pmid: 23212844
	(b) Ai H. J.; Lu W. Y.; Wu X.-F. Angew. Chem. Int. Ed. 2021, 60, 17178. doi: 10.1002/anie.v60.31 pmid: 23212844
	(c) Wang L.-C.; Wu X.-F. Nat. Commun. 2025, 16, 4663. doi: 10.1038/s41467-025-58472-4 pmid: 23212844
[41]	Xiao W.-J.; Alper H. J. Org. Chem. 2001, 66, 6229. pmid: 11559167
[42]	Wang X. H.; Wang B.; Yin X. M.; Yu W. A.; Liao Y.; Ye J. L.; Wang M.; Hu L. R.; Liao J. Angew. Chem. Int. Ed. 2019, 58, 12264. doi: 10.1002/anie.v58.35
[43]	Alper H.; Hamel N. J. Chem. Soc., Chem. Commun. 1990, 135.
[44]	Yu W.-Y.; Bensimon C.; Alper H. Chem. Eur. J. 1997, 3, 417. doi: 10.1002/chem.v3:3
[45]	Cao P.; Zhang X. M. J. Am. Chem. Soc. 1999, 121, 7708. doi: 10.1021/ja991547k
[46]	Shi Z. L.; Shen C. R.; Dong K. W. Chem. Eur. J. 2021, 27, 18039. doi: 10.1002/chem.v27.72
[47]	Dong C.; Alper H. J. Org. Chem. 2004, 69, 5011. doi: 10.1021/jo040109f
[48]	Wang H. N.; Dong B.; Wang Y.; Li J. F.; Shi Y. A. Org. Lett. 2014, 16, 186. doi: 10.1021/ol403171p
[49]	Li J. F.; Chang W. J.; Ren W. L.; Liu W.; Wang H. N.; Shi Y. A. Org. Biomol. Chem. 2015, 13, 10341. doi: 10.1039/C5OB01431J
[50]	Tian D. S.; Xu R. H.; Zhu J. B.; Huang J. X.; Dong W.; Claverie J.; Tang W. J. Angew. Chem. Int. Ed. 2021, 60, 6305. doi: 10.1002/anie.v60.12
[51]	Alper H.; Hamel N. J. Am. Chem. Soc. 1990, 112, 2803. doi: 10.1021/ja00163a053
[52]	Jiang B.; Huang Z.-G.; Cheng K.-J. Heterocycles 2004, 63, 2797. doi: 10.3987/COM-04-10222
[53]	Miquel-Serrano M. D.; Aghmiz A.; Diéguez M.; Masdeu-Bultó A. M.; Claver C.; Sinou D. Tetrahedron: Asymmetry 1999, 10, 4463.
[54]	Huang Z. J.; Cheng Y. Z.; Chen X. P.; Wang H.-F.; Du C.-X.; Li Y. H. Chem. Commun. 2018, 54, 3967. doi: 10.1039/C8CC01190G
[55]	Ji X. L.; Shen C. R.; Tian X. X.; Zhang H. R.; Ren X. Y.; Dong K. W. Angew. Chem. Int. Ed. 2022, 61, e202204156. doi: 10.1002/anie.v61.29
[56]	Marcos-Ayuso G.; Quesada D.; Cobos-Abad M. Y.; Lendínez C.; Fernández-Moyano S.; Mauleón P.; Arrayás R. G. ACS Catal. 2025, 15, 20230. doi: 10.1021/acscatal.5c06941

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