1,4-addition of lithium diisopropylamide to unsaturated esters: role of rate-limiting deaggregation, autocatalysis, lithium chloride catalysis, and other mixed aggregation effects.
Lithium diisopropylamide (LDA) in tetrahydrofuran at -78 °C undergoes 1,4-addition to an unsaturated ester via a rate-limiting deaggregation of LDA dimer followed by a post-rate-limiting reaction with the substrate. Muted autocatalysis is traced to a lithium enolate-mediated deaggregation of the LDA dimer and the intervention of LDA-lithium enolate mixed aggregates displaying higher reactivities than LDA. Striking accelerations are elicited by <1.0 mol % LiCl. Rate and mechanistic studies have revealed that the uncatalyzed and catalyzed pathways funnel through a common monosolvated-monomer-based intermediate. Four distinct classes of mixed aggregation effects are discussed.
Ma
Yun
Y
Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853-1301, USA.
Hoepker
Alexander C
AC
Gupta
Lekha
L
Faggin
Marc F
MF
Collum
David B
DB
D002384:Catalysis; D004952:Esters / Q000737:chemistry*; D005663:Furans / Q000737:chemistry; D007700:Kinetics; D008094:Lithium / Q000737:chemistry*; D018021:Lithium Chloride / Q000737:chemistry; D015394:Molecular Structure; D011437:Propylamines / Q000737:chemistry*
D004952:Esters; D005663:Furans; D011437:Propylamines; C018674:tetrahydrofuran; D008094:Lithium; C007442:diisopropylamine; D018021:Lithium Chloride