[55259-70-6]  · C4H8LiNO  · Lithio-N,N-dimethylacetamide  · (MW 93.05)

(relatively stable enolate;1 used for aldol condensations1,2 and conjugate addition;3 reacts with epoxides;1 can be alkylated1,2 and silylated4)

Physical Data: white solid; 1H NMR (pyridine): 3.15 (d, 1H), 2.93 (d, 1H), 2.63 (s, 6H).

Preparative Methods: by deprotonation of N,N-dimethylacetamide with a variety of bases, most efficiently with Lithium Diisopropylamide in THF at -78 °C or at 0 °C.

Handling, Storage, and Precautions: air and moisture sensitive; solid can be stored for several weeks in sealed bottle; THF solutions are stable for at least several hours at 65 °C.

Aldol Condensations.

Lithio-N,N-dimethylacetamide reacts with a variety of aldehydes or ketones to give b-hydroxy amides in generally good yields,2,5 especially at -78 °C.1 Superior yields, compared to related ester enolates, were obtained with a hindered ketone (eq 1).5b

Asymmetric induction (up to 99% ee) has been reported for condensations with a chiral sulfoxide adjuvant.5c Condensation with an aldehyde imine has been described.5d

Conjugate Addition.

Conjugate addition of the reagent has been reported for nitrostyrenes,3a unsaturated thioamides,3b,c and a vinyl sulfone.3d

Reaction with Epoxides.

The reagent reacts with epoxides in refluxing THF to give g-hydroxy amides.1 Reaction of epoxides with related ester enolates gave lower yields, presumably because of the lesser stability of these enolates.

Alkylation and Silylation Reactions.

The reagent reacts with primary and secondary organic halides to give C-alkylated products without competing dialkylation.1,2 The reagent gives primarily the C-silylated product with Chlorotrimethylsilane and a mixture of O- and C-silylated products with t-Butyldimethylchlorosilane.4

Related Reagents.

t-Butyl a-Lithioisobutyrate; Dilithioacetate; N,N-Dimethyl-2-(trimethylsilyl)acetamide; Ethyl Bromozincacetate; Ethyl Lithioacetate.

1. Woodbury, R. P.; Rathke, M. W. JOC 1977, 42, 1688.
2. Crouse, D. N.; Seebach, D. CB 1968, 101, 3113.
3. (a) Seebach, D.; Leitz, H. F. AG(E) 1971, 10, 501. (b) Tamaru, Y.; Harada, T.; Yoshida, Z. JACS 1979, 101, 1316. (c) Tamaru, Y.; Harada, T.; Nishi, S.; Yoshida, Z. TL 1982, 23, 2383. (d) Hamann, P. R.; Fuchs, P. L. JOC 1983, 48, 914.
4. (a) Hurdlik, P. F.; Peterson, D.; Chou, D. SC 1975, 5, 359. (b) Woodbury, R. P.; Rathke, M. W. JOC 1978, 43, 881.
5. (a) Cuvigny, T.; Hullot, P.; Larcheveque, M.; Normant, H. CR(C) 1974, 279, 569. (b) Sone, T.; Terashima, S.; Yamada, S. CPB 1976, 24, 1293. (c) Annunziata, R.; Cinquini, M.; Cozzi, F.; Montanari, F.; Restelli, A. CC 1983, 1138. (d) Mukaiyama, T.; Goto, Y.; Shoda, S. CL 1983, 671.

Michael Rathke & Robert Elghanian

Michigan State University, East Lansing, MI, USA

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