Synthesis 2011(6): 829-856  
DOI: 10.1055/s-0030-1258379
© Georg Thieme Verlag Stuttgart ˙ New York

Copper-Promoted Carbon-Heteroatom Bond Cross-Coupling with Boronic Acids and Derivatives

Jennifer X. Qiao*, Patrick Y. S. Lam
Research and Development, Bristol-Myers Squibb Company, P.O. Box 5400, Princeton, NJ 08543-5400, USA
Fax: 1(609)8186810; e-Mail:;
Further Information

Publication History

Received 13 September 2010
Publication Date:
22 December 2010 (online)


The discovery of the copper-promoted Chan-Lam coupling reaction with boronic acids more than ten years ago has greatly advanced the carbon-heteroatom cross-coupling chemistry. The N-arylation/O-arylation methodology is now a powerful new synthetic tool, made even more attractive by the mild conditions required. Significant progress has been made in expanding the scope and the applications as well as understanding the mechanism of this reaction. This review includes an examination of various C-X cross-couplings using boronic acids and their derivatives, and a survey of the mechanistic studies that have been carried out.

1 General Introduction

2 C-N Cross-Coupling

2.1 Original NH-Containing Substrates

2.2 Factor Xa Inhibitors

2.3 Selective N-Arylation of Nucleobases

2.4 Additional NH-Containing Substrates

3 C-O Cross-Coupling

3.1 Intermolecular C-O Cross-Coupling

3.2 Intramolecular C-O Cross-Coupling

4 Substrate Selectivity and Reactivity

5 Applications in Solid-Phase Synthesis

6 C-N and C-O Cross-Coupling with Boronic Acid Derivatives

6.1 Boroxines, Boronic Esters, and Trifluoroborate Salts

6.2 Alkenylboronic Acids and Alkynylboronic Acids

6.3 Alkylboronic Acids

7 C-S and C-Se/C-Te Cross-Coupling

8 C-Cl, C-Br, and C-I Cross-Coupling

9 C-C and C-H Cross-Coupling

10 Mechanistic Considerations

10.1 Empirical Observations

10.2 General Mechanistic Observations

10.3 Mechanistic Study of the Catalytic Reaction

11 Other Transition Metals

12 Other Organometalloids

13 Conclusion


Lam, P. Y. S.; Boone, D.; Clark, C. G. unpublished work.


Lam, P. Y. S.; Vincent, G.; Clark, C. G. unpublished work.


Search of natural product database in 1997.


Lam, P. Y. S.; Clark, C. G. unpublished work.


Galemmo, R. A.; Chang, R. K.; Lam, P. Y. S. unpublished work.


Combs, A. P.; Saubern, S.; Lam, P. Y. S. unpublished work.