Enantioselective alkyl-alkyl suzuki cross-couplings of unactivated homobenzylic halides

Journal of the American Chemical Society

Volumn 130, Issue 21, 2008, Pages 6694-6695

  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; NICKEL; ORGANOBORON DERIVATIVE;

ARTICLE; CATALYSIS; CHIRALITY; ENANTIOMER; ENANTIOSELECTIVITY; SUZUKI REACTION;

BENZYL COMPOUNDS; CATALYSIS; HYDROCARBONS, HALOGENATED; NICKEL; PALLADIUM; STEREOISOMERISM;

EID: 44349182541     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja8013677     Document Type: Article

References (25)

1. For two of the pioneering investigations of palladium- and nickel-catalyzed cross-couplings of unactivated alkyl electrophiles, see: (a) Ishiyama, T; Abe, S.; Miyaura, N.; Suzuki, A. Chem. Lett. 1992, 691-694.
2. (b) Devasagayaraj, A.; Stüdemann, T.; Knochel, P. Angew. Chem., Int. Ed. Engl. 1995, 34, 2723-2725.
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. In 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 additional reports of non-asymmetric cross-couplings of unactivated electrophiles, see: (a) Powell, D. A.; Maki, T.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 510-511.
7. (b) González-Bobes, F.; Fu, G. C. J. Am. Chem. Soc. 2006, 128, 5360-5361.
8. (c) Strotman, N. A.; Sommer, S.; Fu, G. C. Angew. Chem., Int. Ed. 2007, 46, 3556-3558.
9. (d) Saito, B.; Fu, G. C. J. Am. Chem. Soc. 2007, 129, 9602-9603.
10. For asymmetric Negishi reactions of activated alkyl electrophiles, see: (a) α-Bromo amides: Fischer, C.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 4594-4595.
11. (b) Benzylic bromides and chlorides: Arp, F. O.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 10482-10483.
12. (c) Allylic chlorides: Son, S.; Fu, G. C. J. Am. Chem. Soc. 2008, 130, 2756-2757.
13. For asymmetric Hiyama reactions of α-bromo esters, see: Dai, X.; Strotman, N. A.; Fu, G. C. J. Am. Chem. Soc. 2008, 130, 3302-3303.
14. For reviews of the Suzuki reaction, see: (a) Miyaura, N. In Metal-Catalyzed Cross-Coupling Reactions; de Meijere, A., Diederich, F., Eds.; Wiley-VCH: New York, 2004; Chapter 2.
15. (b) Handbook of Organopalladium Chemistry for Organic Synthesis; Negishi, E.-i., Ed.; Wiley-Interscience: New York, 2002.
16. (c) Miyaura, N. Top. Curr. Chem. 2002, 219, 11-59.
17. 2O.
18. To the best of our knowledge, these are the first examples of nickel-catalyzed Suzuki reactions of unactivated alkyl electrophiles that proceed below room temperature.
19. Notes: (a) In a gram-scale reaction, the asymmetric Suzuki cross-coupling illustrated in entry 1 of Table 2 was accomplished in 89% ee and 95% yield,
20. (b) During the course of a coupling reaction, the ee of the starting material is less than 10%, and the ee of the product is essentially constant.
21. (c) The ee of the product correlates linearly with the ee of the ligand.
22. (d) For the cross-couplings depicted in Table 2, all of the alkyl bromide has been consumed.
23. For the substrate illustrated in entry 3 of Table 2, the catalyst is effectively differentiating between a benzyl and a homobenzyl substituent.
24. Under our standard conditions, alkylboranes derived from the hydroboration of disubstituted olefins are not suitable reaction partners, and the cross-coupling of a phthalimide-containing alkylborane proceeded in modest yield (∼40%).
25. We speculate that the modest ee observed in entry 4 of Table 3 may be due to competitive coordination of the ether oxygen to the catalyst. Studies directed at exploring this hypothesis are underway.