HMPA organolithium reagents

Organolithium compounds can add to a, (3-unsaturated ketones by either 1,2- or 1,4-addition. The most synthetically important version of the 1,4-addition involves organocopper intermediates, and is discussed in Chap 8. However, 1,4-addition is observed under some conditions even in the absence of copper catalysts. Highly reactive organolithium reagents usually react by 1,2-addition, but the addition of small amounts of HMPA has been found to favor 1,4-addition. This is attributed to solvation of the lithium ion, which attenuates its Lewis acid character toward the carbonyl oxygen.111... 

A similar procedure was used with organolithium reagents [152], and when the reaction was run in ether HMPA was added before the alkylation step. 

Cohen and Liu have examined the yield and selectivity enhancement effects of TMSCl and TMSCl/HMPA on conjugate addition of some stabilized organolithium reagents onto, particularly, easily polymerized a, -unsaturated carbonyl compounds. The authors proposed that the beneficial effect is due to the prevention of 1,2-addition and polymerization of the Q , 8-unsaturated carbonyl compounds. ... 

The effect of ion pair separation on inversion and rotation of S, Se, and Si stabilised organolithium reagents in HMPA has been studied by Li and P NMR and shows... 

The role of HMPA as solvent in the addition of organolithium reagents to enones has been explored by applying a multinuclear NMR technique to quantify the amount of solvent-separated ion pairs (SIP) in solution and to corrolated this with changes in regioisomeric and diastereomeric product ratios.Contact ion pairs (CIP) have been found to react exclusively by 1,2-addition, presumably via a four-centre transition state as hypothesized. However, the situation for SIPs is more complicated and clean 1,4-addition occurs only in the absence of lithium catalysis. Well stabilized anions react by 1,2- and 1,4-addition in the absence of HMPA, when lithium catalysis is possible and SIPs are energetically accessible intermediates. 

The trimethylsilyl radical produced either rapidly dimerizes or reacts with solvent so that very clean ESR spectra of the radical anion, with minimum interactions with the counterion, can be obtained (116). Further reduction to dianions is very slow, and exhaustive reduction to anion radicals minimizes problems associated with exchange between anion radicals and unreduced substrate (115). It now appears that the solvent HMPA greatly facilitates the one-electron reduction, not only for trimethylsilylsodium, but also for organolithium and magnesium reagents (110). It was found that 0.1F solutions of methyl-, n-butyl-, or f-butyllithium or benzylmagnesium chloride will quantitatively reduce biphenyl to its radical anion in less than 10 minutes (110). 

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