Reactivity of the triple ion and separated ion pair of tris(trimethylsilyl) methyllithium with aldehydes: A RINMR study

Article abstract of DOI:10.1021/ja8003528

Low-temperature rapid-injection NMR (RINMR) experiments were performed on tris(trimethylsilyl)methyllithium. In THF/Me₂O solutions, the separated ion (1S) reacted faster than can be measured at -130 °C with MeI and substituted benzaldehydes (k ≥ 2 s^-1), whereas the contact ion (1C) dissociated to 1S before reacting. Unexpectedly, the triple ion reacted faster with electron-rich benzaldehydes relative to electron-deficient ones. The addition of HMPA had no effect on the rate of reaction of the triple ion with p-diethylaminobenzaldehyde, and the immediate product of the reaction was the HMPA-solvated separated ion 1S, with the Peterson product forming only slowly. Thus, the aldehyde is catalyzing the dissociation of the triple ion. HMPA greatly decelerated the reaction of 1S (<10^-10), providing an estimate of the Lewis acid activating effect of a THF-solvated lithium cation in an organolithium addition to an aldehyde. Copyright

Full text of DOI:10.1021/ja8003528

Published on Web 04/18/2008
Reactivity of the Triple Ion and Separated Ion Pair of
Tris(trimethylsilyl)methyllithium with Aldehydes: A RINMR Study
Amanda C. Jones, Aaron W. Sanders, William H. Sikorski, Kristin L. Jansen, and
Hans J. Reich*
Department of Chemistry, UniVersity of Wisconsin, 1101 UniVersity AVenue, Madison, Wisconsin 53706
Received January 15, 2008; E-mail: reich@chem.wisc.edu
Scheme 1. Tris(trimethylsilyl)methyllithium DNMR dynamics in 3:2
The high steric hindrance of tris(trimethylsilyl)methyllithium
THF/Et2O1a
(1) results in unique structural features that allow mechanistic
probes not possible with normal lithium reagents. In THF
solution below -100 °C, 1 exists as three species in slow
exchange on the NMR time scale, the monomeric contact ion
pair 1C, the solvent-separated ion pair 1S, and the dimeric triple
ion 1T (Scheme 1).1a,2 The unprecedented high barriers to
interconversion allowed us to test their individual reactivity
under non-Curtin-Hammet conditions using low-temperature
rapid-injection NMR (RINMR).1b
Injection of methyl iodide into solutions of 1 (Figure 1)
showed no reaction of 1T at -132 °C, but disappearance of
the signals for 1S in less than the time scale of injection and
mixing (1 s, k1S-MeI > 2 s-1),1b and a measurable rate for 1C
(k1C-MeI ) 0.04 s-1). A similar experiment at -86 °C resulted
in immediate (<1 s) disappearance of 1C and 1S and the decay
of 1T over a period of several hours (k1T-MeI ) 3·10-5 s-1).
1T and 1C reacted at rates independent of electrophile concen-
tration,3 thus both must first dissociate to 1S.
From these data, we can calculate that 1S is g50 times as
reactive as 1C toward MeI. An upper limit on the rate MeI reacts
with 1T at -132 °C of k1T-MeI e 4 × 10-10 s-1 can be calculated
from the temperature dependence of the reaction. Thus, 1S is at
least 5 × 1010 times as reactive as 1T. These relative rates are
likely large underestimates since the reaction of 1S is faster and
the reactions of 1T and 1C are slower than the measured rates.
The reaction with aldehydes is more complex.4 The reactivity
profile of 2 and 3 with 1S and 1C was nearly identical to that
of MeI. Conversely, the reaction of 1C in the presence of 4b is
slowed by a factor of 100 compared to the “normal” dissociation
of 1C to 1S. This unexpected effect was not studied.
Since competition experiments are routinely used to measure
relative rates, and from them absolute rates, this reversal merited
some attention. We were aided in this endeavor by observations
on the effect of the strong coordinating solvent HMPA.1c Under
equilibrium conditions, addition of excess HMPA converts 1
+
completely to the separated ion pair 1S (with Li(HMPA)4 as
counterion).1a HMPA solvation resulted in a notable reduction in
reactivity toward aldehydes. The reaction of 1S-HMPA with 2 at
-131 °C was still too fast to measure (k > 2 s-1), but that with 3
was observable (k ) 0.012 s-1). Extrapolation of the observed rates
for 4b from measurements at T > -84 °C gave a k1S-HMPA-4b
)
2.3 × 10-10 s-1 at -131 °C. The aldehydes have the expected
However, all three aldehydes did appear to react with 1T.
Direct rate measurements showed that 1T displayed a reaction
order of 0.8 in 2 due to competitive dissociation to 1S and 1C.
Interestingly, the electron-rich 4 reacts faster than the deficient
2 (krel[direct] in Figure 2). Activation parameters for reaction
of 1T with 2, 3, and 4b were determined from the temperature
dependences of the rates. Extrapolation to -131 °C gave
estimates of k1S/k1T g 220 000 for 4b, g 3.7 × 107 for 3, and
g1.4 × 109 for 2.
1
Figure 1. Selected H NMR spectra (trimethylsilyl signals) and rate plot
of a RINMR experiment of MeI (0.10 mL neat) injected into a solution of
1 (0.02 M) in 1:3 THF/Me2O at ca. -132 °C.
To confirm the inverse of the normally expected Hammett
relationship for the reaction of aldehydes with 1T, we performed
competition experiments. Solutions containing only 1T were
prepared by first scavenging 1C and 1S by addition of MeI at
-78 °C (1T does not react with MeI on this time scale),
followed by the addition of a binary mixture of aldehydes.
Relative rates were calculated from product ratios and were
found to be in the normal order expected for nucleophilic
addition to aldehydes (krel[competition] in Figure 2).
Figure 2. Relative rates of reaction of 1T with aldehydes 2-4 at -78 °C,
measured directly by RINMR or by competition experiments
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6060 J. AM. CHEM. SOC. 2008, 130, 6060–6061
10.1021/ja8003528 CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
dissociation of 1T, but the formed monomers react preferentially
with the more electrophilic 2, giving k2 > k4. The high effectiveness
of 4 as a catalyst for dissociation of 1T can be ascribed to the
small size of the nucleophilic oxygen in 4 compared to that in
HMPA10a (which is an ineffective catalyst).
Using RINMR, competition experiments, and the remarkable
rate-retarding effect of the cosolvent HMPA,11 we have observed
differing rate- and product-determining steps that lead to contradic-
tory rate effects in an organolithium-aldehyde reaction. Given the
enormously greater reactivity of lower over higher aggregates seen
for several lithium reagents and the resultant tendency to dissociate
to lower aggregates prior to reaction,1b,10b,12 the phenomenon
described here is plausible for other reactions with Lewis basic
substrates that can actively participate in the deaggregation process.
This study also illustrates the critical role of lithium catalysis on
carbonyl reactivity.
Figure 3. Injection of an ethereal solution of 4a (1 equiv) and HMPA (5
equiv) into 1 (0.06 M) in 1:3 THF/Me2O at -80 °C.
Scheme 2. Proposed Mechanism
Acknowledgment. The authors wish to thank Dr. Bob Shanks
and Dr. Charlie Fry for NMR assistance, and the NSF for
financial support of this research. The spectrometers are funded
by the NSF (CHF 8306121) and the National Institutes of Health
(NIH 1 S10 RR02388).
Supporting Information Available: Additional experimental
details. This material is available free of charge via the Internet at
http://pubs.acs.org.
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order of reactivity toward 1S-HMPA based on their electrophi-
licities: 2 > 3 . 4b. HMPA retarded the reaction of 4b with 1S
by a factor of at least 1010. This is the first direct measurement of
the Lewis acid activating effect of a THF-solvated lithium cation
in an organometallic addition to an aldehyde.5
If HMPA was injected into a solution of 1 below -70 °C,
1C was rapidly converted to 1S-HMPA. 1T was also converted
to 1S-HMPA but at the same rate as the known dissociation
rate of 1T to 1S/1C in the absence of HMPA. Thus, HMPA
does not assist in the dissociation of 1T by coordination to the
central lithium6 nor does the dissociation involve electrophilic
attack on the triple ion by Li+. This observation, and the fact
that 1S-HMPA reacts only very slowly with 4, allowed a key
experiment that helped identify the source of the reactivity
reversal depicted in Figure 2. If HMPA was first injected into
1 at -94 °C, leading to a solution containing only 1S-HMPA
and 1T, followed by an injection of 4a, then 1T was smoothly
converted to 1S without significant formation of the Peterson
product 5a. The same results were obtained when HMPA and
4a or 4b were injected simultaneously (Figure 3), or when a
catalytic amount of the aldehyde was used. The rate is identical
to the rate of reaction of 4 with 1T in the absence of HMPA.7
Thus 4 catalyzes the dissociation of 1T, but the monomers
formed are inactivated by HMPA. In the absence of HMPA,
1S reacts rapidly with 4.
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substitutions, epoxide openings, and carbonyl additions:1d (a) Sauvetre, R.; Seyden-
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(7) The reaction of 2 with 1T was also unaffected by HMPA.
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to ketones: Asao, N.; Asano, T.; Yamamoto, Y. Angew. Chem., Int. Ed.
2001, 40, 3206.
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We can thus make the proposal shown in Scheme 2. In the
individual kinetic runs, the rate-determining step is aldehyde-
catalyzed dissociation of 1T to the monomers.6 The more basic 4
is a better catalyst than 2 and displays the faster rate by RINMR
kinetic measurements (k4 > k2).8 The likely first formed intermedi-
ate 6, which would normally be considered competent to form
product,9 does not do so but dissociates to 1S, which then adds to
the aldehyde. In competition experiments, the more basic 4 causes
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T. E. J. Am. Chem. Soc. 1973, 95, 8446. (b) Jackman, L. M.; Chen, X.
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(12) Abu-Hasanayn, F.; Streitwieser, A. J. Am. Chem. Soc. 1996, 118, 8136.
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