Zn-Catalyzed Enantio- and Diastereoselective Formal [4 + 2] Cycloaddition Involving Two Electron-Deficient Partners: Asymmetric Synthesis of Piperidines from 1-Azadienes and Nitro-Alkenes

Journal of the American Chemical Society

Volumn 137, Issue 13, 2015, Pages 4445-4452

  Chu, John C K ^a   Dalton, Derek M ^a,b   Rovis, Tomislav ^a  

^a Department of Environmental and Radiological Health Sciences   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HYDROCARBONS; ISOTOPES; LIGANDS; NITROGEN COMPOUNDS; SYNTHESIS (CHEMICAL); ZINC;

ASYMMETRIC SYNTHESIS; CHEMICAL EQUATIONS; CONCERTED MECHANISM; DIASTEREOSELECTIVE; KINETIC ISOTOPE EFFECTS; MICHAEL-TYPE ADDITIONS; ORTHO-SUBSTITUTION; [4 + 2] CYCLOADDITION;

COORDINATION REACTIONS;

1 AZADIENE DERIVATIVE; ALKENE; GLYCERYL TRINITRATE; IMINE; LEWIS ACID; PIPERIDINE DERIVATIVE; UNCLASSIFIED DRUG; ZINC; AMIDE; LIGAND; NITRO DERIVATIVE;

ARTICLE; ASYMMETRIC SYNTHESIS; CATALYSIS; CATALYST; CHEMICAL REACTION; CYCLIZATION; CYCLOADDITION; DIASTEREOISOMER; ELECTROPHILICITY; ENANTIOSELECTIVITY; ENVIRONMENTAL TEMPERATURE; HIGH TEMPERATURE; HYDROGEN BOND; LOW TEMPERATURE; MICHAEL ADDITION; REACTION TIME; STEREOCHEMISTRY; CHEMISTRY; ELECTRON; STEREOISOMERISM;

ALKENES; AMIDES; CATALYSIS; CYCLOADDITION REACTION; ELECTRONS; LIGANDS; NITRO COMPOUNDS; PIPERIDINES; STEREOISOMERISM; ZINC;

EID: 84926483685     PISSN: 00027863     EISSN: 15205126     Source Type: Journal    
DOI: 10.1021/jacs.5b00033     Document Type: Article

References (53)

1. Funel, J.-A.; Abele, S. Angew. Chem., Int. Ed. 2013, 52, 3822 - 3863
2. Nicolaou, K. C.; Snyder, S. A.; Montagnon, T.; Vassilikogiannakis, G. Angew. Chem., Int. Ed. 2002, 41, 1668 - 1698
3. Kagan, H. B.; Riant, O. Chem. Rev. 1992, 92, 1007 - 1019
4. Corey, E. J. Angew. Chem., Int. Ed. 2002, 41, 1650 - 1667
5. Merino, P.; Marques-Lopez, E.; Tejero, T.; Herrera, R. P. Synthesis 2010, 1 - 26
6. Jiang, X.; Wang, R. Chem. Rev. 2013, 113, 5515 - 5546
7. Masson, G.; Lalli, C.; Benohoud, M.; Dagousset, G. Chem. Soc. Rev. 2013, 42, 902 - 923
8. Boger, D. L. Tetrahedron 1983, 39, 2869 - 2939
9. Kouznetsov, V. V. Tetrahedron 2009, 65, 2721 - 2750
10. Fochi, M.; Caruana, L.; Bernardi, L. Synthesis 2014, 135 - 157
11. Behforouz, M.; Ahmadian, M. Tetrahedron 2000, 56, 5259 - 5288
12. Daniels, P. H.; Wong, J. L.; Atwood, J. L.; Canada, L. G.; Rogers, R. D. J. Org. Chem. 1980, 45, 435 - 440
13. Jung, M. E.; Shapiro, J. J. J. Am. Chem. Soc. 1980, 102, 7862 - 7866
14. Jorgensen, K. A. Angew. Chem., Int. Ed. 2000, 39, 3558 - 3588
15. Clark, R. C.; Pfeiffer, S. S.; Boger, D. L. J. Am. Chem. Soc. 2006, 128, 2587 - 2593
16. Esquivias, J.; Arrayas, R. G.; Carretero, J. C. J. Am. Chem. Soc. 2007, 129, 1480 - 1481
17. He, L.; Laurent, G.; Retailleau, P.; Folleas, B.; Brayer, J.-L.; Masson, G. Angew. Chem., Int. Ed. 2013, 52, 11088 - 11091
18. He, M.; Struble, J. R.; Bode, J. W. J. Am. Chem. Soc. 2006, 128, 8418 - 8420
19. Zhao, X.; Ruhl, K. E.; Rovis, T. Angew. Chem., Int. Ed. 2012, 51, 12330 - 12333
20. Jian, T.-Y.; Shao, P.-L.; Ye, S. Chem. Commun. 2011, 47, 2381 - 2383
21. Han, B.; He, Z.-Q.; Li, J.-L.; Li, R.; Jiang, K.; Liu, T.-Y.; Chen, Y.-C. Angew. Chem., Int. Ed. 2009, 48, 5474 - 5477
22. Li, J.-L.; Liu, T.-Y.; Chen, Y.-C. Acc. Chem. Res. 2012, 45, 1491 - 1500
23. Jiang, X.; Shi, X.; Wang, S.; Sun, T.; Cao, Y.; Wang, R. Angew. Chem., Int. Ed. 2012, 51, 2084 - 2087
24. Simal, C.; Lebl, T.; Slawin, A. M. Z.; Smith, A. D. Angew. Chem., Int. Ed. 2012, 51, 3653 - 3657
25. Houk, K. N. Acc. Chem. Res. 1975, 8, 361 - 369
26. Beaudegnies, R.; Ghosez, L. Tetrahedron: Asymmetry 1994, 5, 557 - 560
27. Barluenga, J.; de la Rua, R. B.; de Saa, D.; Ballesteros, A.; Tomás, M. Angew. Chem., Int. Ed. 2005, 44, 4981 - 4983
28. Lin, H.; Tan, Y.; Liu, W.-J.; Zhang, Z.-C.; Sun, X.-W.; Lin, G.-Q. Chem. Commun. 2013, 49, 4024 - 4026
29. For results of the high-throughput screen, please see Supporting Information.
30. The 2:1 adduct is observed by 1H NMR of the unpurified reaction mixture and by MS but has, to date, resisted isolation and characterization.
31. For example, other bisoxazoline ligands such as BOX or PYBOX gives low enantioselectivity. See Supporting Information for details.
32. Lu, S. F.; Du, D.-M.; Xu, J. Org. Lett. 2006, 8, 2115 - 2118
33. Due to the sensitive nature of the tetrahydropyridine, we sought to adopt a reductive workup procedure to reduce the enamine functionality and found that the crude tetrahydropyridine can be reduced to stable 3-nitropiperidine with ZnCl2 and NaBH3CN in MeOH.
34. In constrast to the racemic reaction, ZnI2 does not give any product. Although DME and dioxane are the optimal solvents for the racemic reaction, their use gives lower ee than PhMe. See Supporting Information for the results of solvent screen.
35. Liu, H.; Lu, S.-F.; Xu, J.; Du, D.-M. Chem.-Asian J. 2008, 3, 1111 - 1121
36. The ee values for the Hammett plot were obtained from the average values of three experiments with each ligand.
37. Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165 - 195
38. Kooijman, H.; Spek, A. L.; Zondervan, C.; Feringa, B. L. Acta Crystallogr., Sect. E: Struct. Rep. Online 2002, 58 (8) m429 - 431
39. Nixon, T. D.; Ward, B. D. Chem. Commun. 2012, 48, 11790-11792.
40. There is likely a steric and electronic component to the impact of the ortho substituent given that H, Cl, MeO, and Me provide nearly identical enantioselectivities (68-71% ee).
41. Lykke, L.; Monge, D.; Nielsen, M.; Jorgensen, K. A. Chem.-Eur. J. 2010, 16, 13330 - 13334
42. Since azadiene 1 6 has a poor solubility in PhMe, 32 was used for the kinetic isotope effect studies. Azadiene 32 behaves similarly in all respects to azadiene 16.
43. Van Sickle, D. E.; Rodin, J. O. J. Am. Chem. Soc. 1964, 86, 3091 - 3094
44. Taagepera, M.; Thornton, E. R. J. Am. Chem. Soc. 1972, 94, 1168 - 1177
45. Gajewski, J. J.; Peterson, K. B.; Kagel, J. R.; Huang, Y. C. J. J. Am. Chem. Soc. 1989, 111, 9078 - 9081
46. The p K a's of 4-methoxyaniline and 3-methoxyaniline differ by more than 1 unit.
47. The reactions at rt gave no enantioselectivity.
48. Liu, H.; Li, W.; Du, D.-M. Sci. China, Ser. B: Chem. 2009, 52, 1321 - 1330
49. This observation is consistent with ref 39.
50. For the determination of absolute configuration, see Supporting Information.
51. Unlike the situation when ZnI2 is used as catalyst in absence of BOPA (see Table 1), stirring azadiene 16 with 3 equiv of nitro-alkene 17 with 10 mol % Zn(OTf)2 and F-BOPA ligand at rt for 16 h did not lead to the formation of the 2:1 adduct as judged by MS.
52. There is no reaction at rt without ZnII, so an uncatalyzed pathway can be ruled out. The reaction is also irreversible at rt since no nitro-alkene exchange takes place when the cycloadduct (no reductive workup) is subject to the reaction conditions with another nitro-alkene.
53. Nose, A.; Kudo, T. Chem. Pharm. Bull. 1981, 29, 1159 - 1161