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PdII -Catalyzed Enantioselective C(sp3)-H Arylation of Cyclobutyl Ketones Using a Chiral Transient Directing Group.
Angew Chem Int Ed Engl. 2020 06 08; 59(24):9594-9600.AC

Abstract

The use of chiral transient directing groups (TDGs) is a promising approach for developing PdII -catalyzed enantioselective C(sp3)-H activation reactions. However, this strategy is challenging because the stereogenic center on the TDG is often far from the C-H bond, and both TDG covalently attached to the substrate and free TDG are capable of coordinating to PdII centers, which can result in a mixture of reactive complexes. We report a PdII -catalyzed enantioselective β-C(sp3)-H arylation reaction of aliphatic ketones using a chiral TDG. A chiral trisubstituted cyclobutane was efficiently synthesized from a mono-substituted cyclobutane through sequential C-H arylation reactions, thus demonstrating the utility of this method for accessing structurally complex products from simple starting materials. The use of an electron-deficient pyridone ligand is crucial for the observed enantioselectivity. Interestingly, employing different silver salts can reverse the enantioselectivity.

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Authors+Show Affiliations

Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA.

Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA.

Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA.

Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA.

Discovery Chemistry, Bristol-Myers Squibb, PO Box 4000, Princeton, NJ, 08543, USA.

Discovery Chemistry, Bristol-Myers Squibb Research and Development, 100 Binney Street, Cambridge, MA, 02142, USA.

Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA.

MeSH

BenzeneCatalysisCyclobutanesElectron TransportKetonesPalladiumStereoisomerism

Pub Type(s)

Journal Article

Research Support, N.I.H., Extramural

Language

eng

PubMed ID

32155313

Citation

Xiao, Li-Jun, et al. "PdII -Catalyzed Enantioselective C(sp3)-H Arylation of Cyclobutyl Ketones Using a Chiral Transient Directing Group." Angewandte Chemie (International Ed. in English), vol. 59, no. 24, 2020, pp. 9594-9600.

Xiao LJ, Hong K, Luo F, et al. PdII -Catalyzed Enantioselective C(sp3)-H Arylation of Cyclobutyl Ketones Using a Chiral Transient Directing Group. Angew Chem Int Ed Engl. 2020;59(24):9594-9600.

Xiao, L. J., Hong, K., Luo, F., Hu, L., Ewing, W. R., Yeung, K. S., & Yu, J. Q. (2020). PdII -Catalyzed Enantioselective C(sp3)-H Arylation of Cyclobutyl Ketones Using a Chiral Transient Directing Group. Angewandte Chemie (International Ed. in English), 59(24), 9594-9600. https://doi.org/10.1002/anie.202000532

Xiao LJ, et al. PdII -Catalyzed Enantioselective C(sp3)-H Arylation of Cyclobutyl Ketones Using a Chiral Transient Directing Group. Angew Chem Int Ed Engl. 2020 06 8;59(24):9594-9600. PubMed PMID: 32155313.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - PdII -Catalyzed Enantioselective C(sp3)-H Arylation of Cyclobutyl Ketones Using a Chiral Transient Directing Group. AU - Xiao,Li-Jun, AU - Hong,Kai, AU - Luo,Fan, AU - Hu,Liang, AU - Ewing,William R, AU - Yeung,Kap-Sun, AU - Yu,Jin-Quan, Y1 - 2020/04/01/ PY - 2020/01/12/received PY - 2020/02/11/revised PY - 2020/3/11/pubmed PY - 2021/3/25/medline PY - 2020/3/11/entrez KW - C−H activation KW - arylation KW - palladium KW - pyridone ligands KW - transient directing groups SP - 9594 EP - 9600 JF - Angewandte Chemie (International ed. in English) JO - Angew Chem Int Ed Engl VL - 59 IS - 24 N2 - The use of chiral transient directing groups (TDGs) is a promising approach for developing PdII -catalyzed enantioselective C(sp3)-H activation reactions. However, this strategy is challenging because the stereogenic center on the TDG is often far from the C-H bond, and both TDG covalently attached to the substrate and free TDG are capable of coordinating to PdII centers, which can result in a mixture of reactive complexes. We report a PdII -catalyzed enantioselective β-C(sp3)-H arylation reaction of aliphatic ketones using a chiral TDG. A chiral trisubstituted cyclobutane was efficiently synthesized from a mono-substituted cyclobutane through sequential C-H arylation reactions, thus demonstrating the utility of this method for accessing structurally complex products from simple starting materials. The use of an electron-deficient pyridone ligand is crucial for the observed enantioselectivity. Interestingly, employing different silver salts can reverse the enantioselectivity. SN - 1521-3773 UR - https://www.unboundmedicine.com/medline/citation/32155313/PdII__Catalyzed_Enantioselective_C_sp3__H_Arylation_of_Cyclobutyl_Ketones_Using_a_Chiral_Transient_Directing_Group_ DB - PRIME DP - Unbound Medicine ER -