A R T I C L E S
Zhao and Collum
most useful Bronsted bases in organic chemistry.13 In addition,
the coordination chemistry of LiHMDS solvated by a wide range
of mono- and polydentate ligands has been investigated in
considerable depth, providing sound structural foundations on
which to build an understanding of structure-reactivity relation-
ships.
for example, amine-concentration-dependent reversals in the
relative reactivities that appear quite irrational by normal metrics.
Spectroscopically observable LiHMDS dimer-monomer equi-
10
10,16,20,21
libria,
often ascribed to major changes in reactivity, have
1
5b
no effect on the enolizations.
We traced these baffling reactivities to the relatively simple
dimer-based mechanism depicted in Scheme 1. From a tactical
perspective, it is notable how spectroscopic and kinetic methods
combine to provide insight into weak solvent-lithium interac-
tions and other elusive phenomena. On a practical level, the
rate increases caused by adding low concentrations of simple
trialkylamines to LiHMDS/toluene solutions may be useful to
synthetic organic chemists. A summary of the structural and
rate studies is presented at the beginning of the discussion for
the convenience of the reader.
We report detailed investigations of the LiHMDS-mediated
enolization of 2-methylcyclohexanone (1; eq 1) in the presence
14,15a
of a broad range of di- and trialkyl-amines (Charts 1 and 2).
The selected relative rate constants (krel) shown in eq 1 set the
tenor of this paper by highlighting a number of unusual effects.
Results
Structures of LiHMDS and Amine Classifications. Exten-
6
15
22
sive structural studies of [ Li, N]LiHMDS solvated by di-
and trialkylamines using a combination of one- and two-
6
15
dimensional Li and N NMR spectroscopies provide an
1
6
For example, the marked rate accelerations affiliated with the
excellent foundation for the rate studies. Although additional
NMR spectroscopic studies were required to fill in some details,
the methods are now well established and the results are
incremental. Accordingly, some new results are simply archived
in the Supporting Information. A few key observations are
mentioned in the appropriate context below.
poorly coordinating1
6,17
trialkylamines may be somewhat sur-
prising given that high reactivity is often associated with strongly
coordinating solvents.1 (By comparison, the analogous eno-
lization of 1 using 6.0 equiv of THF affords krel ) 20.) The
apparent inverse correlation of the enolization rate with increas-
ing steric demand and rate maxima when amines of intermediate
steric requirements are used seems especially difficult to
explain.19 The 300-fold decline in the rate caused by replacing
n-Bu3N with n-Bu2Ni-Bu is stunning. Other oddities not
captured by the data in eq 1 are also noteworthy. We will show,
1,18
The widely varying solvent effects described in this paper
derive from only a few underlying principles. Nonetheless,
maintaining adequate perspective during the presentation can
be daunting. Consequently, we have classified the amines into
four general types to clarify the results and discussion. We
summarize results from prior studies of LiHMDS in solution
in the context of the amine classifications as follows.
(
9) For reviews of structural investigations of lithium amides, see: Gregory,
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(1) Type I. Additions of g1.0 equiv of relatively unhindered
amines quantitatively convert a mixture of higher oligomer 7
(
(
(
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(
13) For selected examples in which LiHMDS is used on large scale, see:
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19, 4765. Also, see ref 36.
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5
3
73. (b) The results for LiHMDS/Et N-mediated enolization have been
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(
(
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