Physical properties
Lithium 2,2,6,6-Tetramethylpiperidide exists in THF solution as a dimer-monomer equilibrium mixture; additives such as HMPA
increase monomer concentration. X-ray structure determination shows that LiTMP crystallizes as a
tetramer from hexane/pentane mixtures.
Uses
Lithium 2,2,6,6-tetramethylpiperidide is a strong base and can be used:
- For the synthesis of enamines from terminal epoxides through trans-α-lithiated epoxide as an intermediate.
- For ortholithiation of arenes such as 1,3-bis(trifluoromethyl)benzene, 4,4-dimethyl-2-phenyl-2-oxazoline, 1,4-bis(trifluoromethyl)benzene and 1,3-dimethoxybenzene.
- In combination with Lewis donor ligand, N,N,N′,N′-tetramethylethylenediamine (TMEDA) for deprotonative metalation of methoxy-substituted arenes.{21]
Application
Lithium 2,2,6,6-Tetramethylpiperidide (LTMP) is a strong, highly hindered, nonnucleophilic base (pKa = 37.3) capable of selective deprotonation of aromatics,
heteroaromatics, and aliphatic C-H acidic sites in the presence of a variety of functional groups; also
compatible with several electrophiles for in situ quenching of kinetically derived lithiated species.
Preparation
Preparative Method of Lithium 2,2,6,6-Tetramethylpiperidide: prepared in Et2O or THF solutions immediately before use by treatment of
commercially available dry 2,2,6,6-Tetramethylpiperidine with n-Butyllithium (1:1). Tetramethylpiperidine
is dried by heating a mixture of the base with CaH2 at reflux for 4 h in a preflamed flask, followed by
distillation at atmospheric pressure (bp 152 °C). It should be stored in a septum sealed bottle.
storage
LiTMP solutions are pyrophoric, can cause severe burns, and should
always be handled and transferred under an inert atmosphere. Solutions of LiTMP show a loss of activity
(50% in THF; 60% in Et2O) after 12 h at 24 °C. Use in a fume hood.
