A Relative Organolithium Stability Scale Derived from Tin−Lithium Exchange Equilibria. Substituent Effects on the Stability of α-Oxy- and α-Aminoorganolithium Compounds

Abstract

Quantitative thermodynamic stability scales of organolithium compounds can be derived from measurements of tin-lithium exchange equilibria. A DeltaG(eq) scale of alpha-oxy- and alpha-aminoorganolithium compounds was established, and quantitative stabilization effects of O-alkyl, O-alkoxyalkyl, O-carbamoyl, N-carbamoyl, and O-carbonyl groups of the alpha-carbanion are presented. It has been found that an alpha-oxycarbanion is far better stabilized by a carbonyl group as the O-substituent than by an alkyl or alkoxyalkyl group, while the anion-stabilizing effects of the different O-carbonyl substituents are comparable. An N-carbamoyl group was found to have a somewhat higher stabilizing effect than its O-carbamoyl counterpart. NMR data are presented that show that benzylic N- or O-substituted carbanions have highly planarized structures where the negative charge is highly delocalized. The stability data obtained from the tin-lithium exchanges can be easily converted into "effective pK" data that are useful for predicting the acid-base behavior of this type of organolithium species.

Quantitative Data on the Effects of Alkyl Substituents and Li–O and Li–N Chelation on the Stability of Secondary α‐Oxy‐Organolithium Compounds

“…From Fraser's original p K data in tetrahydrofuran we calculated the Δ G eq values8 shown in Figure 1. The reference level of 0.0 kcal mol −1 was assigned to 9‐xanthenyllithium, the most stable reference compound used in our previous study 2. As a first test of our method we chose to measure the relative stabilities of the reference aromatic and heteroaromatic compounds 1 – 6 in order to check if our measurements were congruent with Fraser's basicity scale.…”

“…The concentrations of the relevant stannanes and organolithium species at equilibrium were measured by NMR or GC after low‐temperature protonation with deoxygenated methanol (see ref. 2 for details). The reverse reaction was performed in every case to ensure that the equilibrium point had been reached.…”

“…A particularly interesting aspect of the chemistry of this type of compounds is how substituents (both proximate and remote to the carbanionic center) influence the stability of these organolithium species. Quantitative data on this fundamental question is still lacking for the most part, due to the difficulty of establishing a general quantitative thermodynamic stability scale of organolithium compounds 2. Traditionally, the stabilities of organolithium compounds have been determined by measuring the p K of the corresponding carbanions,3 but the application of this approach to the more basic, highly functionalized, more synthetically useful organolithium reagents is problematic, especially in ethereal solvents, despite of the fact that Streitwieser4 has provided data for several types of aromatic, heteroaromatic, and benzylic systems, obtained using this method.…”

“…We have recently reported the measurement of the relative stabilities of α‐heterosubstituted‐benzylic organolithium compounds in tetrahydrofuran, thus providing for the first time quantitative data on the effects of the heteroatom adjacent to the carbanionic center, as well as those of the heteroatom's substituents, on the stabilities of these type of highly functionalized organometallics 2. Our approach is based on the establishment of a Sn–Li exchange between the organolithium under study and a reference compound (as shown in Equation (1) (see below), an equilibrium reaction which favors the pairing of the most stable carbanion with the more electropositive Li atom 5.…”

Direct metalation of methoxymethyl arylmethyl ethers: A tin-free approach to the generation of α-alkoxyalkoxy-substituted aryllithiums

“…Indeed, the most widely employed procedure for the generation of these organometals involves condensation of lithium tributylstannane with an aromatic aldehyde, followed by protection of the resulting a-tributylstannyl-substituted benzyl alcohol, and final tin-lithium exchange (Scheme 1) [9][10][11][12][13][14][15][16][17].…”