Aminolithiation of carbon-carbon double bonds as a powerful tool in organic synthesis

Abstract

A conjugate amination of α,β-unsaturated carbonyl compounds with lithium amides has become a powerful method of N-C bond-forming reactions. Chiral ligand-controlled asymmetric version of the conjugate amination of enoates was developed for practical bench chemistry, giving the enantioenriched amination product with over 99 % ee. In situ diastereoselective alkylation of resulting lithium enolates allowed us to form vicinal N-C and C-C bonds in a one-pot operation. This protocol enabled us to realize a short-step asymmetric synthesis of otamixaban key intermediate. Treatment of product 3-benzylamino-and 3-allylaminoesters with tert-butyllithium gave five-or seven-membered lactams through [1,2]-or [2,3]-rearrangement of intermediate β-lactams. Isolated C-C double bonds were also found to accept intramolecular aminolithiation affording the corresponding hydroamination products. Chiral lithiophilic ligand-catalyzed reaction gave enantioenriched hydroamination products with high ee. Stereoselective intramolecular aminolithiation of allylaminoalkenes was coupled with subsequent carbolithiation to give doubly cyclized product amines.

Easy Routes towards Chiral Lithium Binaphthylamido Catalysts for the Asymmetric Hydroamination of Amino‐1,3‐dienes and Aminoalkenes

“…Since only rare examples of asymmetric hydroamination/cyclisation of aminoalkenes promoted by lithium base catalysts have been reported,5a–5c our next goal was to study the efficiency of the diaminobinaphthyllithium salts described above for such reactions (Scheme ). Catalysts prepared according to Methods A, B and C were first compared for the cyclisation of two substrates.…”