New experimental conditions for tandem hydroalumination/Cu-catalyzed asymmetric conjugate additions to β-substituted cyclic enones

Organic Letters

Volumn 13, Issue 12, 2011, Pages 3040-3043

  Müller, Daniel ^a   Tissot, Matthieu ^a   Alexakis, Alexandre ^a  

^a UNIVERSITY OF GENEVA   (Switzerland)

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Indexed keywords

EID: 79958853047     PISSN: 15237060     EISSN: 15237052     Source Type: Journal    
DOI: 10.1021/ol200898c     Document Type: Article

References (28)

1. Wilke, G.; Müller, H. Justus Liebig Ann. Chem. 1960, 629, 222-240
2. For two examples of racemic conjugate addition reactions, see: Ireland, R. E.; Wipf, P. J. Org. Chem. 1990, 55, 1425-1426
3. Wipf, P.; Smitrovich, J. H.; Moon, C. J. Org. Chem. 1992, 57, 3178-3186 For two examples of tandem hydroalumination-ACA reactions affording products in 50-73% ee, see: Vuagnoux-d'Augustin, M.; Alexakis, A. Chem.-Eur. J. 2007, 13, 9647-9662
4. Palais, L.; Alexakis, A. Chem.-Eur. J. 2009, 15, 10473-10485
5. Zweifel, G.; Miller, J. A. Org. React. 1984, 32, 375
6. For observations of the harmful effect of acetylides in ACA reactions, see: Corey, E. J.; Kwak, Y. Org. Lett. 2004, 6, 3385-3388
7. May, T. L.; Dabrowski, J. A.; Hoveyda, A. H. J. Am. Chem. Soc. 2011, 133, 736-739
8. The use of Si-protected alkynes to circumvent Al-acetylide formation is a well-known strategy; see ref 3.
9. For one example using (E)-1-iodohex-1-ene as a nucleophile precursor, see: Hawner, C.; Li, K.; Cirriez, V.; Alexakis, A. Angew. Chem., Int. Ed. 2008, 47, 8211-8214 For a more general disclosure affording product in up to 96% ee, see: Müller, D.; Hawner, C.; Tissot, M.; Palais, L.; Alexakis, A. Synlett 2010, 1694-1698
10. 2Al-vinylalanes and therefore show higher reactivity.
11. For formation of <2% of Al-acetylide, see ref 3.
12. 6% of Al-acetylide formation for the hydroalumination of hexyne; see ref 3.
13. For instance, such a substance might be LiCl, which was shown to decrease enantioselectivities; see ref 7b.
14. Gao, F.; Hoveyda, A. H. J. Am. Chem. Soc. 2010, 132, 10961-10963
15. In the absence of a Ni catalyst usually high levels of Al-acetylide formation (>20%) is observed; see ref 12.
16. See the Supporting Information for details.
17. For the synthesis of SimplePhos Ligands, see: Palais, L.; Mikhel, I. S.; Bournaud, C.; Micouin, L.; Falciola, C. A.; Vuagnoux-d Augustin, M.; Rosset, S.; Bernardinelli, G.; Alexakis, A. Angew Chem. Int. Ed. 2007, 46, 7462-7465
18. Reference 2d.
19. Bournaud, C.; Falciola, C.; Lecourt, T.; Rosset, S.; Alexakis, A.; Micouin, L. Org. Lett. 2006, 8, 3581-3584
20. This has been observed previously; see ref 2c.
21. Concerning the selectivities of L2 and L3a, most of the reactions showed differences in enantioselectivities of <15%. However, L3a gives higher enantioselectivities for 5- and 7-membered substrates, whereas L2 affords particularly high enantioselectivities for sterically demanding substrates or nucleophiles.
22. Unpublished results.
23. 3 did not accelerate such reactions; see ref 2b.
24. Cycloheptenones prooved to be inefficient in catalysis with Si-protected alkenyl alanes; see ref 5.
25. L2 and L4 afforded inferior enantioselectivities for the addition of trialkylaluminum to β-substituted cyclopentenones compared to the cyclohexenone counterparts; see refs and 2d.
26. Alexakis, A.; Duffault, J. M. Tetrahedron Lett. 1988, 29, 6243-6246
27. For the β-styrenyl adduct there has been only precedence for Si-protected alkenyl alanes; see ref 5.
28. As previously observed, β-styrenylalane adds much faster than the α-styrenylalane, see ref 7b.