Catalytic asymmetric synthesis of a tertiary benzylic carbon center via phenol-directed alkene hydrogenation

Journal of Organic Chemistry

Volumn 76, Issue 13, 2011, Pages 5198-5206

  Caille, Seb ^a   Crockett, Rich ^a   Ranganathan, Krishnakumar ^a   Wang, Xiang ^a   Woo, Jacqueline C S ^a   Walker, Shawn D ^a  

^a AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKENE HYDROGENATION; ASYMMETRIC SYNTHESIS; ASYMMETRIC TRANSFORMATIONS; BENZYLIC CARBON; BUILDING BLOCKES; CYCLOPENTANONE; DRUG CANDIDATES; ENANTIOSELECTIVE HYDROGENATION; GRIGNARD ADDITION; PHENOL GROUPS; SYNTHETIC APPROACH;

HYDROGENATION; KETONES; OLEFINS; RARE EARTH ELEMENTS;

PHENOLS;

ALKENE; BENZYL DERIVATIVE; BUTYRONITRILE; CARBON; CYCLOPENTANONE DERIVATIVE; ISOBUTYRONITRILE; KETONE; LANTHANIDE; LITHIUM CHLORIDE; PHENOL; UNCLASSIFIED DRUG;

ARTICLE; ASYMMETRIC CATALYSIS; ASYMMETRIC SYNTHESIS; CHIRALITY; COST EFFECTIVENESS ANALYSIS; DRUG SYNTHESIS; GRIGNARD REACTION; HYDROGENATION; SCALE UP; STEREOSPECIFICITY;

ALKENES; CATALYSIS; HYDROGENATION; MOLECULAR STRUCTURE; PHENOLS; STEREOISOMERISM;

EID: 79959666316     PISSN: 00223263     EISSN: 15206904     Source Type: Journal    
DOI: 10.1021/jo200941r     Document Type: Article

References (25)

1. For examples of asymmetric arylation of ketones, see: Liao, X.; Weng, Z.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130, 195-200
2. Hamada, T.; Chieffi, A.; Ahman, J.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 1261-1268
3. Ahman, J.; Wolfe, J. P.; Troutman, M. V.; Palucki, M.; Buchwald, S. L. J. Am. Chem. Soc. 1998, 120, 1918-1919 For a review on asymmetric conjugate addition to enones, see: Hawner, C.; Alexakis, A. Chem. Commun. 2010, 46, 7295-7306
4. Application of the method described in this manuscript to the asymmetric synthesis of tolterodine has been reported by our group: Wang, X.; Guram, A.; Caille, S.; Hu, J.; Preston, J P.; Ronk, M.; Walker, S. Org. Lett. 2011, 13 (7) 1881-1883
5. Appell, R. A. Urology 1997, 50, 90-96
6. Price of 3 from Sigma-Aldrich: ∼$2.5/g on 5 g scale. We experienced difficulties sourcing 3 as several suppliers failed to deliver the requested material because of the use of inadequate synthetic routes (>20 g scale).
7. Synthesis of 11: Larcheveque, M.; Debal, A.; Cuvigny, T. Bull. Soc. Chim. Fr. 1974, 1710-1714
8. Synthesis of 3 from 11: Larcheveque, M.; Debal, A.; Cuvigny, T. J. Organomet. Chem. 1975, 87, 25-31
9. The preparation of the ethyl ester variant of 12 has been reported: Kopp, F.; Krasovskiy, A.; Knochel, P. Chem. Commun. 2004, 2288-2289
10. The rate of deprotonation of cyclopentanones by basic reagents has been shown to be higher than that associated with the deprotonation of cyclohexanones or acyclic ketones: Shechter, H.; Collis, M. J.; Dessy, R.; Okuzumi, Y.; Chen, A. J. Am. Chem. Soc. 1962, 84, 2905-2910 Consequently, this undesired reaction pathway is particularly problematic in the case of addition of basic nucleophiles to cyclopentanones.
11. Reported yields improve drastically for addition of Grignards reagents to cyclopentanone derivatives if the transformations are performed in the presence of lanthanide salts. For examples, see: Imamoto, T.; Takiyama, N.; Nakamura, K.; Hatajima, T.; Kamiya, Y. J. Am. Chem. Soc. 1989, 111, 4392-4398
12. Dimitrov, V.; Bratovanov, S.; Simona, S.; Kostova, K. Tet. Lett. 1994, 35, 6713-6716
13. Krasovskiy, A.; Kopp, F.; Knochel, P. Angew. Chem., Int. Ed. 2006, 45, 497-500
14. Lightfoot, A.; Schnider, P.; Pfaltz, A. Angew. Chem., Int. Ed. 1998, 37, 2897-2899
15. The cost of the Na salt of BARF is $100/g on a 100 g scale (SynQuest Fluorochemicals).
16. Burk, M. J.; Wang, Y. M.; Lee, J. R. J. Am. Chem. Soc. 1996, 118, 5142-5143
17. Under nonoptimized distillation conditions, dodecane was only partially separated from 3 and the isolated material contained 32.4 wt% of dodecane. High purity 3 (>96 wt%) from Aldrich was utilized to screen the lanthanide-catalyzed Grignard addition reaction.
18. Although n -butyllithium was also a suitable mediator, the byproduct octane (bp 126 °C) could not be readily separated from 3.
19. When benzaldehyde was added to the Grignard reagent instead of ketone 3, alcohol 18 was isolated in 72% yield.
20. Conlon, D. A.; Kumbe, D.; Moeder, C.; Hardiman, M.; Hutson, G.; Sailer, L. Adv. Synth. Catal. 2004, 346, 1307-1315
21. Due to the necessity to filter these solids, the stoichiometry of Ce relative to that of Li in the final lanthanide solution cannot be assessed with certainty.
22. Concentrations of La and Ce were measured by ICP-MS.
23. The Grignard addition performed at 23 °C with substrates 12a and 12b produced complex mixtures of products.
24. Limanto, J.; Shultz, C. S.; Dorner, B.; Desmond, R. A.; Devine, P. N.; Krska, S. W. J. Org. Chem. 2008, 73, 1639-1642
25. A complete substrate scope for this transformation has been reported separately: Wang, X.; Guram, A.; Caille, S.; Hu, J.; Preston, J P.; Ronk, M.; Walker, S. Org. Lett. 2011, 13 (7) 1881-1883