Selective lithiation of 2-methyloxazoles. Applications to pivotal bond constructions in the phorboxazole nucleus.
[formula: see text] The lithiation of 2-methyloxazoles with alkyllithium and hindered lithium amide bases generally results in the competitive formation of a mixture of 5-lithio- and 2-(lithiomethyl)oxazole isomers. Herein a synthetically useful lithiation method which allows for the selective formation of 2-(lithiomethyl)oxazole is described. Diethylamine has been found to be a kinetically competent proton source that will mediate the equilibration of the kinetically formed 5-lithiooxazole to its more stable 2-(lithiomethyl)oxazole counterpart. Application of this metalation strategy with lithium diethylamide to two important bond constructions relevant to a projected phorboxazole synthesis is presented.
Evans
D A
DA
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. evans@chemistry.harvard.edu
Cee
V J
VJ
Smith
T E
TE
Santiago
K J
KJ
D000478:Alkylation; D007700:Kinetics; D018020:Lithium Compounds / Q000737:chemistry*; D010080:Oxazoles / Q000737:chemistry*
D018020:Lithium Compounds; D010080:Oxazoles