Autocatalysis in lithium diisopropylamide-mediated ortholithiations.
Ortholithiation of 3-fluorophenyl-N,N-diisopropyl carbamate by lithium diisopropylamide (LDA) in THF at -78 degrees C affords unusual rate behavior including linear decays of the carbamate, delayed formation of LDA-aryllithium mixed dimers, and evidence of autocatalysis. A mechanistic model in conjunction with numeric integration methods accounts for the time-dependent changes in concentration. The two critical rate-limiting steps in the model entail (1) an LDA dimer-based metalation of arylcarbamate, and (2) a rate-limiting condensation of the resulting aryllithium with the LDA dimer to form two isomeric LDA-ArLi mixed dimers. One isomer elicits a highly efficient (post-rate-limiting) metalation of aryl carbamate, in turn, regenerating aryllithium. The prevalence and implications of such autocatalysis are discussed.
Singh
Kanwal J
KJ
Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853-1301, USA.
Hoepker
Alexander C
AC
Collum
David B
DB
D002219:Carbamates / Q000737:chemistry*; D002384:Catalysis; D007700:Kinetics; D008094:Lithium / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009942:Organometallic Compounds / Q000138:chemical synthesis*; D011437:Propylamines / Q000737:chemistry*; D012996:Solutions
D002219:Carbamates; D009942:Organometallic Compounds; D011437:Propylamines; D012996:Solutions; D008094:Lithium; C007442:diisopropylamine