Diastereoselection in the formation of spirocyclic oxindoles by the intramolecular heck reaction

Journal of Organic Chemistry

Volumn 71, Issue 7, 2006, Pages 2587-2599

  Overman, Larry E ^a   Watson, Donald A ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIZATIONS; INSERTION TOPOGRAPHY; QUATERNARY STEREOCENTERS;

ATOMS; CARBONYLATION; CONFORMATIONS; HYDROGEN BONDS; MOLECULAR PHYSICS; STEREOCHEMISTRY; SUBSTRATES;

ORGANIC COMPOUNDS;

AMIDE; CARBON; CARBONYL DERIVATIVE; CYCLOHEXENE DERIVATIVE; DIAMIDE; HYDROGEN; OXINDOLE; PENTANE; SPIROOXINDOLE; UNCLASSIFIED DRUG; VINYL DERIVATIVE;

ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CHEMICAL BOND; CHEMICAL STRUCTURE; CYCLIZATION; DIASTEREOISOMER; HECK REACTION; PROTON NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS; STEREOCHEMISTRY; STRUCTURE ANALYSIS; SYNTHESIS;

CRYSTALLOGRAPHY, X-RAY; CYCLIZATION; INDOLES; MODELS, MOLECULAR; MOLECULAR CONFORMATION; SPIRO COMPOUNDS; STEREOISOMERISM;

EID: 33645516369     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo052335a     Document Type: Article

References (54)

1. (a) Dounay, A. B.; Overman, L. E. Chem. Rev. 2003, 103, 2945-2964.
2. (b) Link, J. T. The Intramolecular Heck Reaction. In Organic Reactions; Overman, L. E., Ed.; John Wiley and Sons: New York, 2002; Vol. 60, pp 157-534.
3. (c) Overman, L. E.; Link, J. T. Intramolecular Heck Reactions in Natural Products Chemistry. In Metal Catalyzed Cross-Coupling Reactions; Stang, P. J., Diederich, F., Eds.; Wiley-VCH: New York, 1998.
4. (d) de Meijere, A.; Brase, S. Palladium-Catalyzed Coupling of Organyl Halides to Alkenes - The Heck Reaction. In Metal Catalyzed Cross-Coupling Reactions; Stang, P. J., Diederich, F., Eds.; Wiley-VCH: New York, 1998.
5. (e) de Meijere, A.; Meyer, F. E. Angew. Chem., Int. Ed. Engl. 1994, 33, 2379-2411.
6. Overman, L. E.; Paone, D. V.; Stearns, B. A. J. Am. Chem. Soc. 1999, 121, 7702-7003.
7. There are limited methods known for the construction of contiguous all-carbon quaternary centers. To our knowledge, the examples described from our laboratories are the only catalytic reactions reported for the synthesis of vicinal quaternary carbon stereocenters. See: Peterson, E. A.; Overman, L. E. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 11943-11948.
8. For general methods for the construction of quaternary carbon stereocenters, see: (a) Douglas, C. J.; Overman, L. E. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5363-5367.
9. (b) Denissova, I.; Barriault, L. Tetrahedron 2003, 59, 10105-10146.
10. (c) Christoffers, J.; Baro, A. Angew. Chem., Int. Ed. 2003, 42, 1688-1690.
11. (d) Christoffers, J.; Mann, A. Angew. Chem., Int. Ed. 2001, 40, 4591-4597.
12. (e) Corey, E. J.; Guzman-Perez, A. Angew. Chem., Int. Ed. 1998, 37, 388-401.
13. Stearns, B. A. A Formal Synthesis of Loracarbef and Total Synthesis of Polypyrrolidinoindoline Alkaloids. Ph.D. Thesis, University of California-Irvine, Irvine, CA, 2000.
14. Overman, L. E.; Watson, D. A. J. Org. Chem. 2006, 71, 2600-2608.
15. To allow complete conversion of intermediates produced from the ditriflate precursor to the observed final products 4 and 10-12, longer reaction times were required than those in the cyclizations of the corresponding diiodide.
16. See Supporting Information for additional details.
17. 6
18. Emerman, S. L.; Meinwald, J. J. Org. Chem. 1956, 21, 375.
19. Bald, E.; Saigo, K.; Mukaiyama, T. Chem. Lett. 1975, 1163-1166.
20. A minor byproduct from the competitive oxidation of the cyclohexadiene to the corresponding arene was observed also in the epoxidation step. This material proved difficult to separate from the desired product prior to conversion to diol 15.
21. Maier, G.; Sayrac, T.; Reisenauer, H. P. Chem. Ber. 1982, 115, 2202-2213.
22. Attempts to use other nucleophiles in this reaction, in particular anilines or their metal salts, led to complex mixtures of products.
23. Other activation strategies, such as the use of Mukaiyama's salt, provided the coupled product in low yield only. Increased steric crowding imparted by the proximity of the C2 ester likely makes amide formation more challenging in this series.
24. The choice of ethyl ether as the solvent proved critical in this sequence; the use of methylene chloride as solvent yielded only trace amounts of product.
25. (a) Basha, A.; Lipton, M.; Weinreb, S. M. Tetrahedron Lett. 1977, 48, 4171-4174.
26. (b) Willimas, J. M.; Jobson, R. B.; Yasuda, N.; Marchesini, G.; Dolling, U. H.; Grabowski, E. J. J. Tetrahedron Lett. 1995, 36, 5461-5464.
27. Watson, D. A. Investigation into the Origins of Diastereoselection in Spirocyclic Oxindole Forming Intramolecular Heck Cyclizations. Ph.D. Thesis, University of California-Irvine, Irvine, CA, 2004.
28. Alkyne 24a is available in one step from propiolic acid and N-benzylaniline.
29. Several reagents were examined as promoters for this coupling, but only carbodiimide reagents were successful.
30. 2AlCl did not promote the reaction at room temperature.
31. (b) Substoichiometric quantities of 2,6-di-tert-butyl-4-methylpyridine were added to prevent Brönsted acid-promoted side reactions such as alkene migration.
32. Crow, W. D.; Leonard, N. J. J. Org. Chem. 1965, 30, 2660-2665.
33. McMurry, J. E.; Scott, W. J. Tetrahedron Lett. 1983, 24, 979-982.
34. Cacchi, S.; Ciattini, P. G.; Morera, E.; Ortar, G. Tetrahedron Lett. 1986, 37, 3931-3934.
35. Collins, C. J.; Martinez, A. G.; Alvarez, R. M.; Aguirre, J. A. Chem. Ber. 1984, 117, 2815-2824.
36. This ratio matches the ratio previously observed in a similar reaction. See: Abelman, M. M.; Oh, T.; Overman, L. E. J. Org. Chem. 1987, 52, 4130-4133.
37. Resubjection of the isolated products to the cyclization conditions resulted in no further alkene migration.
38. 29
39. Available from Schrödinger, L. L. C., 101 SW Main Street, Suite 1300, Portland, OR 97204.
40. 18
41. 29 Transition states were characterized by a single imagery frequency. The energies reported were calculated at 373K, corresponding to the experimental reaction temperature for the Heck cyclizations.
42. For computational ease, a methylidene acetyl was used in place of the acetonide, the benzyl group was replaced with a hydrogen atom, and a phosphine replaced the triphenylphosphine.
43. 373 favored the transition state leading to the observed diastereomer by approximately the same energetic difference. Details of these additional calculations can be found in the Supporting Information.
44. Amatore, C.; Jutand, A. Acc. Chem. Res. 2000, 33, 314-321 and references therein.
45. For both methyl ester 20a and dimethyl amide 29c, X-ray crystallographic studies revealed two conformations in the solid state that differ in the orientation of the triflato anilide substituent about the C2-C7 bond (Figure 4). In both conformations, the amides adopt nonconjugated conformations. For clarity, Figure 8 shows only one of these conformations. Complete depictions of the unit cells of the compounds can be found in the Supporting Information.
46. X-ray crystallographic studies were also performed on ditriflate 1b and dianilide 29a. The results from these studies show similar amide conformations to that of 29c and are presented in the Supporting Information.
47. 18 as well as crystallographic data, show that the two possible conformations of the C2 amides have similar energies. Therefore, diastereoselection in the Heck cyclizations of these substrates does not derive from the ground-state conformational preferences of the amide.
48. This analysis assumes a relatively early transition state for the migratory insertion. As previously argued, the trend of increased diastereoselection with large C2 amides precludes a late transition state, as the developing 1,3-diaxial interaction between the amide and the C4 hydrogen atom would result in lowered diastereoselection.
49. The developing C-Pd bond in 58 and 59 is long and, therefore, the potential steric interactions between it and the adjacent hydrogen atoms are expected to be of minimal consequence.
50. Similar gearing effects have been previously noted in other systems, see, inter alia: (a) Roush, W. R.; Lane, G. C. Org. Lett. 1999, 1, 95-98.
51. (b) Walsh, P. J.; Lurain, A. E.; Balsells, J. Chem. Rev. 2003, 103, 3297-3344.
52. 2 More than this factor must be involved as disiloxy triflate 16b, which lacks a C2 substituent, cyclized with no stereoselectivity.
53. (a) General experimental details have been described: MacMillan, D. W. C.; Overman, L. E.; Pennington, L. D. J. Am. Chem. Soc. 2001, 123, 9033-9044.
54. (b) CCDC 288970-288975 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.