Low-temperature rapid injection NMR (RINMR) experiments were performed on two lithium reagents, n-butyllithium and 2-methoxy-6-(methoxymethyl)phenyllithium (5), with the goal of measuring the relative reactivity of the different aggregates (dimer, mixed dimer, and tetramer for n-BuLi, monomer and tetramer for 5) toward typical electrophiles. The reaction of the n-BuLi dimer with (trimethylsilyl)acetylene first forms the mixed dimer n-BuLi·Me3SiC⋮CLi, which is about 1/60 as reactive as the n-BuLi homodimer. The tetramer does not react. In the deprotonation of (phenylthio)acetylene, the n-BuLi dimer was found to be 3.5 × 108 as reactive as the tetramer, and in the addition to p-diethylaminobenzaldehyde, the relative reactivity was at least 2 × 104. In the deprotonation of (p-tolylsulfonyl)acetylene, the monomer of 5 was at least 1014 times as reactive as the tetramer. These measurements show that the difference in reactivity between the lower and higher aggregates of organolithium reagents can be many orders of magnitude higher than all previous estimates.
A kinetic study of the effect of added HMPA cosolvent on the reaction of 2-lithio-1,3-dithiane (1), bis(phenylthio)methyllithium (2), and bis(3,5-bistrifluoromethylphenylthio)methyllithium (3) with methyloxirane (propylene oxide), N-tosyl-2-methylaziridine, and the several alkyl halides (BuCl, BuBr, BuI, allyl chloride) was carried out. Widely varied rate effects of HMPA on these SN2 substitutions were observed, ranging from >108 rate increases for 1 and butyl chloride to >103 rate decreases for 3 and methyloxirane. These reactions appear to go through separated ion pair intermediates, so a key effect is the ease of ion pair separation of the lithium reagent (3 > 2 > 1). Because 3 is already almost fully separated in THF, HMPA has no effect on the rate of halide substitution, but a large reduction is observed with the epoxide as substrate, a consequence of strong lithium assistance to the ring opening which is suppressed when excess HMPA is present. When ion pair separation is difficult (1), modest rate increases (104) are seen for epoxide opening, but very large increases are seen for aziridine (106) and alkyl halide reactions (108), for which lithium assistance is much less important. Reagent 2 shows more complicated behavior in reaction with the epoxide: 1-2 equiv of HMPA causes a small rate increase, while larger amounts cause a large rate decrease. Here the rate-accelerating effects of SIP formation are more nearly balanced with the rate-retarding effects of suppression of lithium catalysis.
This paper is dedicated to Professor Dieter Seebach in honor of his 65th birthday Hypervalent ate complexes are presumptive intermediates in the metal-halogen, metal-tellurium, and related exchange reactions. The effect of o,o'-biphenyldiyl vs. diphenyl substitution on formation of tellurium ate complexes was studied by a kinetic technique and by NMR spectroscopy. Only a modest increase in the association constant (K ate ) was measured. When Li/M exchanges of o,o'-biphenyldiyl sulfides and selenides were made intramolecular by means of a m-terphenyl framework (12-S, 12-Se, 21), enormous increases (> 10 9 ) in the rate of Li/S and Li/Se exchange were observed compared to acyclic models. Apparently, these systems are ideally preorganized to favor the T-shaped geometry of the hypervalent intermediates. For the selenium systems, ate complex intermediates (20-Se, 26) were detected spectroscopically in THF-or THF/HMPA-containing solutions. A DNMR study showed that Li/Se exchange was substantially faster than exchange of the lithium reagents with the ate complex. Therefore, these ate complexes are not on the actual Li/Se exchange pathway.Introduction. ± The lithium-metalloid exchange reaction is the mildest and most general procedure for the preparation of organolithium reagents. The lithium-bromine [1] [2a] and lithium-iodine exchanges have been the most popular, but the reaction applies to many of the main-group third-, fourth-, and fifth-row elements. Tin [3a] [4], selenium (first studied by Seebach and Peleties [3b], and tellurium [3c] have been used extensively. The reaction fails with second-row CÀM bonds like those of chlorides, sulfides, and phosphines, except in exceptional circumstances, e.g., when there are no protons that can be metallated, when an unusually stable carbanion is being prepared, or when a strained ring is being cleaved [5] [6].Hypervalent ate complexes such as 1 ± 3 have been spectroscopically characterized and are likely intermediates in the degenerate phenyl-phenyl Li/I [7a] [7b] [8] [9], Li/Te [7b] [7c] [10a], and Li/Sn [7d] [11] [12] exchange reactions. Ate complexes of third-and even second-row metalloids Se, P, and Si can be detected in favorable structures, e.g., when the aryl groups are heavily substituted with electronegative halogen atoms (4, see [10b]) or when o,o'-biphenyldiyl ligands are present (5, see [13] and 6, see [14a]).
The lithium±metalloid exchange reaction is widely used to prepare synthetically valuable organolithium reagents. The full synthetic potential of one of the most important of these reactions, the Li/I exchange, was not realized (e.g., in the synthesis of alkyllithium reagents) until mechanistic studies showed that it was a well-behaved polar process without a significant radical component. [1a, b, 2] Ate complexes, first proposed by Wittig and Schˆllkopf, [3] are presumptive intermediates in these reactions [Eq. (1)]. Ate complexes of iodine, [1a,b, 4] tellurium, [1b, 5] selenium, [1c, 5] tin, [1d, 6] and silicon [7] having only alkyl and aryl ligands have been characterized in solution and in the solid state, and probed by high-level calculations. [8] Their presence, however, is not proof that they are intermediates in the exchange. No direct evidence has been reported for any Li/M exchange which shows that all of the exchange proceeds along path k ate , and none by the direct exchange path k d , which bypasses the ate complex [Eq. (1)]. To perform such an experiment with dynamic NMR (DNMR) spectroscopy, the three reactants (monomeric ArLi, ArM, and Ar 2 MLi) in the triangular equilibrium of Equation (1) must be present in detectable concentrations under conditions for which the rates k d , k ate , and k 0 ate can each be measured. A number of Li/I and Li/Te exchanges we investigated failed to provide a clear answer. Exchanges of PhI and Ph 2 Te with PhLi could not be analyzed because no solvent of appropriate polarity was found such that all species were detectable. In THF both monomer and dimer were observable, but the equilibrium constant K eq [Eq. (1)] for the ate complex was so high that insufficient PhLi and/or PhI/Ph 2 Te (whichever was stoichiometrically limiting) was present. [1b] In less polar, mixed solvents, the concentration of PhLi monomer was too low for proper line-shape analysis [1e, 9] (the dimer of PhLi is not active in the exchange process [1b] ). A problem which prevents kinetic analysis of Li/I exchanges is the fast reaction between ArI and the ate complex, in which the latter ZUSCHRIFTEN 3586
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