Dual mechanisms of an organocatalytic homodimerization reaction

Tetrahedron Letters

Volumn 51, Issue 38, 2010, Pages 5086-5090

  Guidi, Vanina ^a   Sandoval, Sergio ^a   McGregor, Michael A ^a   Rosen, William ^a  

^a University of Rhode Island   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 CYCLOHEXENONE; ENAMINE; IMINE; PROLINE;

ARTICLE; CATALYSIS; CHEMICAL REACTION KINETICS; CYCLOADDITION; DIELS ALDER REACTION; DIMERIZATION; ISOLATION PROCEDURE;

ALNUS;

EID: 78549262336     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2010.07.114     Document Type: Article

References (19)

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10. Ohkite, M.; Tsuji, T.; Nishida, S. Chem. Commun. 1991, 37.
11. General procedure for preparation of 1: Freshly distilled amine (1-10 mmol) and L-proline (0.1-0.5 equiv mmol) were stirred while 2-cyclohexenone (1- 10 mmol) was added. This mixture was stirred for the designated period of time and then an aliquot was withdraw, dissolved in diethyl-ether and analyzed by GC/ESI-MS to determine the intermediates. For the analysis of the ratio of homodimer isomers aq acid was added to the ether solution followed by the same analysis after drying the ether layer.
12. 3): σ = 22, 23, 28, 30, 44, 45, 60, 61, 110, 164, 166 ppm.
13. At the suggestion of a referee we have included the mass of intermediate molecular ions determined by GC/ESI-MS. These M+ mass values (amu) were characterized by their associated cracking patterns. [Note for example: Schmid, M.B.; Zeitler, K.; Gschwind, R.M. Angew. Chem., Int. Ed, 2010 49, 4997.]
14. 2) in the first step thus determines the ultimate stereochemical result of homodimerization.
15. Homodimers produced by hydrolysis of 6 and 60 may be one of several ratelimiting steps in the crude reaction mixture where the concentration of H2O is very low. [For example: Wiesner, M.; Upert, G.; Angelici, G.; Wennemers, H. J. Am. Chem. Soc. 2010, 132, 6.]
16. The L-proline organocatalyst must be present to derive either of the homodimeric isomers and thus it dictates the two-step mechanistic pathway that produces exo-1 initially in preference to endo-1. This two-step mechanism can in theory also deliver the endo-1 isomer [3 (Re) + E,S-5 (Re) first step9a] but this latter two-step pathway must surmount a higher barrier than the former mechanism. The one-step and energetically similar H-bond assisted Diels- Alder reaction to this latter pathway can derive endo-1 with pyrrolidine but an acid catalyst5,6a is required.
17. Westermann, B.; Ayaz, M.; van Berkel, S. S. Angew. Chem., Int. Ed. 2010, 49, 846;
18. Grondel, C.; Jeanty, M.; Enders, E. Nat. Chem. 2010, 2, 167.
19. The racemic nature of isolated 4.HCl is due to the excess base that was utilized in the organocatalytic reaction. Pyrrolidine, a fairly strong base (pκã 11.3), is able to initiate either an isomerization or racemization process during the course of the reaction. [For example: Blackmond, D.G.; Moran, A.; Hughes, M.; Armstrong, A. J. Am. Chem. Soc. 2010, 132, 7598.]