Alkyl-alkyl Suzuki cross-couplings of unactivated secondary alkyl halides at room temperature

Journal of the American Chemical Society

Volumn 129, Issue 31, 2007, Pages 9602-9603

  Saito, Bunnai ^a   Fu, Gregory C ^a  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKYL GROUP; HALIDE;

ARTICLE; CATALYSIS; CATALYST; COMPLEX FORMATION; QUANTUM YIELD; REACTION ANALYSIS; ROOM TEMPERATURE; SUZUKI REACTION;

ALKYLATION; ELECTRONS; HALOGENS; LIGANDS; MOLECULAR STRUCTURE; TEMPERATURE;

EID: 34547789922     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja074008l     Document Type: Article

References (20)

1. For general reviews of metal-catalyzed cross-coupling reactions, see: (a) Metal-Catalyzed Cross-Coupling Reactions; de Meijere, A., Diederich, F., Eds.; Wiley-VCH: New York, 2004.
2. (b) Handbook of Organopalladium Chemistry for Organic Synthesis; Negishi, E.-i., Ed.; Wiley-Interscience: New York, 2002.
3. For reviews of cross-coupling reactions of alkyl electrophiles, see: (a) Frisch, A. C.; Beller, M. Angew. Chem., Int. Ed. 2005, 44, 674-688.
4. (b) Netherton, M. R.; Fu, G. C. Topics in Organometallic Chemistry: Palladium in Organic Synthesis; Tsuji, J., Ed.; Springer: New York, 2005.
5. (c) Netherton, M. R.; Fu, G. C. Adv. Synth. Catal. 2004, 346, 1525-1532.
6. For two pioneering investigations of palladium- and nickel-catalyzed cross-couplings of alkyl electrophiles, see: (a) Ishiyama, T.; Abe, S.; Miyaura, N.; Suzuki, A. Chem. Lett. 1992, 691-694.
7. (b) Devasagayaraj, A.: Stüdemann, T.; Knochel, P. Angew. Chem., Int. Ed. Engl. 1995, 34, 2723-2725.
8. For additional leading references, see: Terao, J.; Kambe, N. Bull. Chem. Soc. Jpn. 2006, 79, 663-672.
9. Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 14726-14727.
10. For reviews of the Suzuki reaction, see: (a) Reference 1.
11. (b) Miyaura, N. Top. Curr. Chem. 2002, 219, 11-59.
12. (a) Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2004, 126, 1340-1341.
13. (b) González-Bobes, F.; Fu, G. C. J. Am. Chem. Soc. 2006, 128, 5360-5361.
14. Notes: (a) Certain other alcohols (2,2-dimethyl-1-propanol, 2-ethyl-1-butanol, and s-BuOH) furnish comparable or slightly diminished yields, (b) In the presence of KOi-Bu (1.2 equiv), rather than KOt-Bu/i-BuOH, the desired product is generated in 74% yield.
15. For discussions of transmetalation in the context of palladium-catalyzed Suzuki reactions, see: (a) Matos, K.; Soderquist, J. A. J. Org. Chem. 1998, 63, 461-470.
16. (b) Miyaura, N. J. Organomet. Chem. 2002, 653, 54-57.
17. A competition experiment among secondary alkyl halides revealed the following reactivity order: I > Br ≫ Cl.
18. Preliminary experiments indicate that, under our standard reaction conditions, alkylboranes derived from the hydroboration of more highly substituted olefins, as well as alkylboron reagents that bear certain nitrogen-containing functional groups, are not suitable cross-coupling partners. Furthermore, couplings of activated secondary alkyl halides (i.e., a benzylic bromide and an α-bromoester) have not proceeded cleanly. We intend to explore the use of different ligands and reactions conditions to address these limitations.
19. In the case of the coupling depicted in entry 9 of Table 2, we have determined that undesired products from elimination, reduction, or homocoupling of the alkyl bromide are not formed in significant yields.
20. 2(9-BBN) proceeds in <5% yield).