'Counter-intuitive' regioselectivity, subtle steric and solvation effects in lithiation of cyclic tertiary aralkylamines

Tetrahedron Letters

Volumn 46, Issue 39, 2005, Pages 6753-6755

  Kessar, Satinder V ^a   Singh, Paramjit ^a   Singh, Kamal Nain ^a   Venugopalan, P ^a   Kaur, Amarjit ^a   Mahendru, Manu ^a   Kapoor, Rajiv ^a  

^a PANJAB UNIVERSITY   (India)

Author keywords

Amines; Lithiation; Regioselectivity; Solvent effects; Steric effects

Indexed keywords

AMINE; BENZYL DERIVATIVE; COORDINATION COMPOUND; LITHIUM DERIVATIVE; NITROGEN; SOLVENT;

ARTICLE; LITHIATION; SOLVATION; STEREOSPECIFICITY;

EID: 23944455841     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2005.07.110     Document Type: Article

References (29)

1. H. Gilman, and R.V. Young J. Am. Chem. Soc. 56 1934 1415 1416
2. G. Wittig, and G. Fuhrmann Chem. Ber. 73 1940 1197 1218
3. H.W. Gschwend, and H.R. Rodriguez Org. React. 26 1979 1
4. Z. Rappoport I. Marek The Chemistry of Organolithium Compounds 2004 Wiley New York
5. C. Najera, M. Yus, and R. Chinchilla Tetrahedron 61 2005 3139 3176 (symposium in print on functionalized organolithium compounds)
6. M.C. Whisler, S. MacNeil, V. Snieckus, and P. Beak Angew. Chem., Int. Ed. 43 2004 2206 2225
7. The disinclination for intra-complex α-lithiation has been noted occasionally and considered 'counter-intuitive', see: H. Luitjes, M. Schakel, M.P. Aarnts, R.F. Schmitz, F.Z.J. de Kanter, and G.W. Klumpp Tetrahedron 53 1997 9977 9988
8. In freely folding systems coordination effects can be felt across a large number of bonds, see: P. Linnane, N. Magnus, and P. Magnus Nature 385 1997 799 801
9. K.M.B. Gross, and P. Beak J. Am. Chem. Soc. 123 2001 315 319
10. Electronic effects which include electronegativity, polarizability, low lying orbitals and lone pair repulsions are well known to fall off rapidly with distance.
11. D.B. Collum Acc. Chem. Res. 10 1992 448 454
12. J.M. Saà, G. Martorell, and A. Frontera J. Org. Chem. 61 1996 5194 5195
13. We use the term 'distal' for lithiations in which monomeric RLi complexed to the heteroatom remains, in less strained geometries, too distant from the C-H center for effective bonding in the transition state. In aggregate, different lithium atoms may participate in coordination and bonding, see: J.R. Nicolaas, V.E. Hommes, and P.v.R. Schleyer Tetrahedron 50 1994 5903 5916 and
14. D. Seebach Angew. Chem., Int. Ed. Engl. 27 1988 1624 1654
15. A cyclic aralkylamine framework is present in a large number of compounds with pharmacological activity: M. Shamma The Isoquinoline Alkaloids, Chemistry and Pharmacology 1972 Academic Press New York
16. J. Blagg, S.J. Coote, and G. Davies J. Chem. Soc., Perkin Trans. 1 1987 689 694
17. U.S. Patent 4,107,303, 1978; Chem. Abstr. 1978, 90, 87307.
18. N.S. Narasimha, P.S. Chandrachood, and N.R.T. Shete Tetrahedron 37 1981 825 827
19. S.V. Kessar, and P. Singh Chem. Rev. 97 1997 721 737
20. R.E. Gawley, and I. Coldham The Chemistry of Organolithium Compounds 2004 Wiley New York pp 997-1055
21. 3 activation route (Ref. 14). The question of kinetic versus thermodynamic control was not addressed. However, in reactions in which the temperature was not raised to 0 °C, yields were lower but no change in the product profile was detected.
22. Crystallographic data (excluding structure factors) for the structures 3c and 4c in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication numbers CCDC 266706 and 266707. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44 (0)12223 336033 or e-mail: deposit@ccdc.cam.ac.uk ].
23. N. Tomooka, T. Nakai, L.F. Wang, and F. Okazaki Tetrahedron Lett. 41 2000 6121 6125
24. In hydrocarbon solvents, tetramers of sec-BuLi are known to predominate, while in THF, dimers, and monomers are present roughly in a ratio of 1:4, see: W. Bauer, W.R. Winchester, and P.v.R. Schleyer Organometallics 6 1987 2371 2379
25. Y. Ito, M. Nakatsuka, and T. Saegusa J. Am. Chem. Soc. 104 1982 7609 7622
26. R. Maggi, and M. Schlosser J. Org. Chem. 61 1996 5430 5434
27. With 6a TMEDA suppresses the yield (Table 1, entry 7) and Schlosser's base gives an α-substitution product, see: H. Albrecht, J. Herbach, T. Hauck, and H.O. Kalinowski Chem. Ber. 125 1992 1753
28. Notably, eight-membered amine 3a is lithiated at the γ-position, in preference to the β-position, (Table 1, entry 3) while β-lithiated N,N-dimethylphenethylamine undergoes rapid fragmentation, see: D.W. Slocum, and C.A. Jennings J. Org. Chem. 41 1976 3653 3664
29. Exploratory studies with conformationally rigid or restricted systems to chart patterns of regioselectivity and in-depth spectroscopic, rate law, and computational studies are needed for further understanding.