Asymmetric construction of quaternary carbon stereocenters: High stereoselection in Mukaiyama aldol reactions of 2-siloxyindoles with chiral aldehydes

Organic Letters

Volumn 7, Issue 13, 2005, Pages 2795-2797

  Adhikari, Susanta ^a   Caille, Sebastien ^a,b   Hanbauer, Martin ^a,c   Ngo, Vinh X ^a   Overman, Larry E ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b AMGEN INC   (United States)

^c DSM Fine Chemicals Austria Nfg GmbH & Co KG   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

ALDEHYDE; INDOLE ALKALOID; INDOLE DERIVATIVE; ORGANOMETALLIC COMPOUND; SILICON;

ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; STEREOISOMERISM; SYNTHESIS;

ALDEHYDES; INDOLE ALKALOIDS; INDOLES; MOLECULAR STRUCTURE; ORGANOMETALLIC COMPOUNDS; SILICON; STEREOISOMERISM;

EID: 29844452098     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol051172+     Document Type: Article

References (25)

1. For recent reviews of enantioselective generation of quaternary stereocenters, see: (a) Douglas, C. J.; Overman, L. E. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5363-5367.
2. (b) Denissova, I.; Barriault, L. Tetrahedron 2003, 59, 10105-10146.
3. (c) Christoffers, J.; Baro, A. Angew. Chem., Int. Ed. 2003, 42, 1688-1690.
4. (d) Christoffers, J.; Mann, A. Angew. Chem., Int. Ed. 2001, 40, 4591-4597.
5. (e) Corey, E. J.; Guzman-Perez, A. Angew. Chem., Int. Ed. 1998, 37, 388-401.
6. Takahashi, C.; Numata, A.; Ito, Y.; Matsumura, E.; Araki, H.; Iwaki, H.; Kushida, K. J. Chem. Soc., Perkin Trans. 1 1994, 1859-1864.
7. Takahashi, C.; Minoura, K.; Yamada, T.; Numata, A.; Kushida, K.; Shingu, T.; Hagishita, S.; Nakai, H.; Sato, T.; Harada, H. Tetrahedron 1995, 51, 3483-3498.
8. Klebe, J. F.; Finkbeiner, H.; White, D. M. J. Am. Chem. Soc. 1966, 88, 3390-3395.
9. Rh(II)-catalyzed reaction with a diazoketone: (a) Sawada, T.; Fuerst, D. E.; Wood, J. L. Tetrahedron Lett. 2003, 44, 4919-4921.
10. Mukaiyama aldol reaction with formaldehyde: (b) Nicolaou, K. C.; Hao, J.; Reddy, M. V.; Rao, P. B.; Rassias, G.; Snyder, S. A.; Huang, X.; Chen, D. Y.-K.; Brenzovich, W. E.; Giuseppone, N.; Giannakakou, P.; O'Brate, A. J. Am. Chem. Soc. 2004, 126, 12897-12906.
11. For a recent authoritative review, see: Carreira, E. Mukaiyama Aldol Reaction. In Comprehensive Asymmetric Catalysis; Jacobsen, E., Pfaltz, E., Yamamoto, Y., Eds.; Springer: Berlin, 1999; Vol. 3, pp 997-1065.
12. Mukaiyama, T.; Banno, K.; Narasaka, K. J. Am. Chem. Soc. 1974, 96, 7503-7509.
13. The closest analogy, of which we are aware, to the chemistry reported herein is the high selectivity reported for the reaction of silylketene acetals derived from methyl 2-methoxypropionate and (S)-2-(phenylmethoxy)-propanal in the Heathcock group's asymmetric synthesis of L-cladinose: Montgomery, S. H.; Pirrung, M. C.; Heathcock, C. H. Carbohydr. Res. 1990, 202, 13-32.
14. Garner, P.; Park, J. M. Organic Syntheses; Wiley: New York, 1998; Collect. Vol. IX, pp 300-305.
15. Muthusamy, S.; Gunanathan, C.; Babu, S. A.; Suresh, E.; Dastidar, P. J. Chem. Soc., Chem. Commun. 2002, 824-825.
16. Attempted aldol reaction of the lithium enolate of 6 (LDA, THF, -78°C, 1 h) and 8 (in the presence or absence of HMPA or DMPU) at temperatures from -78°C to room temperature resulted only in the recovery of starting materials.
17. 13
18. (b) A similar reaction was seen with congeners of 7 in which the siloxyindole nitrogen was protected with a p-methoxybenzyl or SEM group; however, the reaction failed if this substituent was Boc or TBDMS.
19. Carriera, E. M.; Singer, R. A. Tetrahedron Lett. 1994, 35, 4323-4326.
20. (a) Adduct 9 and related Mukaiyama aldol products having aryl substituents at C3 undergo rapid retro-aldolization in the presence of base and fragment slowly even under neutral conditions. This lability complicates purification of these products.
21. (b) No isomers were seen by HPLC analysis. Stereoselectivity is estimated to be at least 80:1 as isomer ratios of 90:1 could be measured in this way.
22. 13C NMR spectra because of carbamate rotamers. Confirmation by NMR of high isomeric purity of 9 (at least > 15: 1) is possible at the stage of 11, a derivative showing sharp NMR signals.
23. X-ray analysis carried out with ent-12 prepared from the reaction of 7 and ent-8.
24. A preference for forming the syn stereoisomer is observed also in condensations of 13 with achiral aldehydes such as 4-phenylbutanal. Stereoselection is substantial (15-40:1) when R = 3-(1-benzylindolyl) [relative configuration by X-ray analysis] and modest (3-4:1) when R = 3,4-dimethoxyphenyl.
25. 6 Further studies will be needed before a model for the stereoselective reactions reported herein can be advanced.