Lithium t-Butyl-t-octylamide

[90702-60-6]  · C12H26LiN  · Lithium t-Butyl-t-octylamide  · (MW 191.33)

(relatively accessible hindered amide base)

Alternate Name: LOBA.

Preparative Methods: a variety of di-t-alkylamines which are more hindered than the commercially available 2,2,6,6-Tetramethylpiperidine can be prepared by multistep routes;1-4 the precursor to LOBA, 1,1,3,3-tetramethylbutyl-t-butylamine, is obtained in three steps from commercially available materials in an overall yield of 73%;4 LOBA is prepared by metalation of this amine with Methyllithium; metalation with BuLi occurs sluggishly, if at all.

Handling, Storage, and Precautions: lithium amide bases are reactive to air and water; use in a fume hood.

Selective Enolate Formation.

In a comparison with Lithium Diisopropylamide, LOBA exhibits greater regioselectivity (eq 1) and greater stereoselectivity (eq 2) in the formation of ketone and ester enolates, as judged by an in situ quenching procedure using Chlorotrimethylsilane (TMSCl).5,6

Ester (1), an intermediate in a synthesis of pseudomonic acid C,7 is converted by the Ireland-Claisen rearrangement,8 using LDA, into a 4:1 mixture of epimers (2) and (3) (eq 3). Lithium 2,2,6,6-Tetramethylpiperidide and LOBA give higher selectivities (6:1 and 7:1, respectively) but the yield is much lower (<30%).

Related Reagents.

See entries for similar amide bases, e.g. Lithium Amide, Lithium Diethylamide, Lithium Diisopropylamide, Lithium 2,2,6,6-Tetramethylpiperidide, Potassium Diisopropylamide.

1. Schwartz, M. A.; Hu, X. TL 1992, 33, 1689.
2. Klusener, P. A. A.; Tip, L.; Brandsma, L. T 1991, 47, 2041.
3. Kopka, I. E.; Fataftah, Z. A.; Rathke, M. W. JOC 1980, 45, 4616.
4. Corey, E. J.; Gross, A. W. TL 1984, 25, 491.
5. Corey, E. J.; Gross, A. W. TL 1984, 25, 495.
6. For an explanation of the changes in selectivity observed with in situ quenching compared to external quenching in related systems, see: Hall, P. L.; Gilchrist, J. H.; Collum, D. B. JACS 1991, 113, 9571.
7. Barrish, J. C.; Lee, H. L.; Mitt, T.; Pizzolato, G.; Baggiolini, E. G.; Uskokovic, M. R. JOC 1988, 53, 4282.
8. Ireland, R. E.; Mueller, R. H.; Willard, A. K. JACS 1976, 98, 2868.

Michael Rathke & Robert Elghanian

Michigan State University, East Lansing, MI, USA

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