Reversible enolization of beta-amino carboxamides by lithium hexamethyldisilazide.
The enolization of beta-amino carboxamides by lithium hexamethyldisilazide (LiHMDS) in THF/toluene and subsequent diastereoselective alkylation with CH(3)I are reported. In situ IR spectroscopic studies reveal that beta-amino carboxamides coordinate to LiHMDS at -78 degrees C before enolization. Comparison with structurally similar carboxamides suggests that the beta-amino group promotes the enolization. IR spectroscopic studies also show that the enolization is reversible. Efficient trapping of the enolate by CH(3)I affords full conversion to products. (6)Li and (15)N NMR spectroscopic studies reveal that lithium enolate-LiHMDS mixed dimers and trimers as well as a homoaggregated enolate are formed during the reaction. At ambient temperature, racemization of the beta-position through a putative reversible Michael addition was observed.
McNeil
Anne J
AJ
Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853-1301, USA.
Collum
David B
DB
D000478:Alkylation; D000577:Amides / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry*; D007700:Kinetics; D018020:Lithium Compounds / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D012821:Silanes / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism
D000577:Amides; D000596:Amino Acids; D018020:Lithium Compounds; D012821:Silanes; C442341:lithium hexamethyldisilazide