Regioselective Asymmetric α,α-Bisalkylation of Ketones via Complex-Induced Syn-Deprotonation of Chiral N-Amino Cyclic Carbamate Hydrazones

• DOI: 10.1021/ja202267k
• Publication Date: 2011-04-21T15:03:30Z
• Authors: Sarah E. Wengryniuk; Daniel Lim; Don M. Coltart
• Keywords: Lithium diisopropylamide; Diastereomer

The first general method for the asymmetric α,α-bisalkylation of ketones having both α- and α'-protons is described. Both excellent regio- stereoselectivity result. transformation enabled by complex-induced syn-deprotonation (CIS-D), which completely reverses inherent preference lithium diisopropylamide (LDA) to remove less sterically hindered two similarly acidic protons. CIS-D also overrides normal tendency LDA more strongly proton in a substrate protons differing significantly their acidity. regiochemical outcome is, thus, opposite that normally obtained kinetic LDA-mediated deprotonation (S)-1-amino-2-methoxymethylpyrrolidine/(R)-1-amino-2-methoxymethylpyrrolidine (SAMP/RAMP)hydrazones. Conveniently, this strategy allows access either ketone enantiomer using single auxiliary. utility demonstrated concise highly efficient formal synthesis (R)- (S)-stigmolone.