SELECTIVE NUCLEOPHILIC-ADDITION REACTIONS OF ALKYLLITHIUM REAGENTS WITH N-(TRIMETHYLSILYL)LACTAMS - SYNTHESIS OF CYCLIC KETIMINES

In our studies of the enantioselective synthesis of alkaloids via chiral a-sulfinyl ketimines,1'2 cyclic ketimines of various ring size and containing diverse substituents, e.g. la-h, were required. Four methods have been reported for the synthesis of cyclic ketimines: (1) additions of organolithium reagents to N-vinyllactams,3 (2) acid-catalyzed rearrangement of tertiary azides,4 (3) palladium-catalyzed oxidation of amino alkenes,5 and (4) additions of organo-lithium6 or Grignard reagents7 with lactim ethers. Method 1 requires N-vinyllactams of which, however, only N-vinylpyrrolidinone is commercially available. Bayer and Geckeler8 have noted the difficulty of obtaining N-vinyl-lactams in their report on the transvinylation of imides and e-caprolactam with vinyl acetate in the presence of sodium tetrachloropalladate. We found that under these conditions $-valerolactam (3d) was converted into N-vinyl-valerolactam in only a 20% yield (60% recovery of $-valerolactam). Method 2 requires a sequence of three steps, two of which utilize HN3-BF3.ether and H2S04, respectively. Acid-labile systems like tert-butyldi-methylsilyl ethers are incompatible with the reagents. Method 3 leads to a mixture of 2-ethyl-l-pyrroline and 2-methyl-1-piperidine (1d) in a ratio of 1:2. And, method 4 fails to provide Id and l-aza-2-methyl-l-cycloheptene (le). Herein, we describe a convenient method to prepare cyclic ketimines 1 in high yield from readily available N-(trimethylsilyl) lactams 2. © 1990, American Chemical Society. All rights reserved.