A computational study of halomethyllithium carbenoid mixed aggregates with lithium halides and lithium methoxide
Graphical abstract
Introduction
Lithium carbenoids are used extensively in organic synthesis. In addition to cyclopropanation reactions with alkenes, carbenoids undergo a variety of single bond insertion reactions, including both C–H and C–heteroatom insertions. The instability and reactivity of lithium carbenoids makes them difficult to study by conventional experimental methods, although low temperature 13C NMR spectroscopy has been used for structure determination of a few of the more stable haloalkyllithium carbenoids.1, 2 Those investigations proved the carbene-like character of the halomethyllithium species from the lithium–carbon spin coupling constants, but provided no information on the aggregation behavior of lithium carbenoids. To date little is known about the detailed reaction mechanisms of these compounds, and several research groups have turned to computational studies to investigate the structure and reactions of these species in more detail. Cyclopropanation reactions have been the subject of several theoretical investigations of monomeric lithium and zinc carbenoids in the gas phase.3, 4, 5
Nearly all organolithium compounds can exist as aggregates, and lithium carbenoids are no exception. A previous computational study showed that halomethyllithium carbenoids dimerize in the gas phase and sometimes in ethereal solvents.6 Small changes in the structure of lithium compounds or in solvation can cause significant changes in the aggregation behavior. Mixed aggregates between two different lithium compounds are also quite common and can have significant effects on the product distribution. This was illustrated by several studies on lithium dialkylamide mixed aggregates and their effect on the stereochemistry of ketone enolization.7, 8, 9, 10, 11, 12
A clear picture of the reactions of lithium carbenoids is beginning to emerge, and will almost certainly include homo- and mixed aggregates. Nakamura and co-workers showed that monomeric lithium and zinc carbenoids can react with alkenes either in a concerted or stepwise manner.3 Our own work, currently in progress, suggests that the concerted mechanism is also operative in the lithium carbenoid dimer. The monomer and homo-dimer are likely reactive species at the beginning of lithium carbenoid reactions before much lithium halide byproduct has been formed. We hypothesize that the lithium halide byproduct will form mixed aggregates with the halomethyllithium carbenoids, similar to those that have recently been reported with lithium dialkylamides.13 Likewise, exposure of the reaction mixture, or the alkyllithium used to generate the carbenoid, to small amounts of air will result in the formation of lithium alkoxides. Of course, either of those compounds can be intentionally added to the reaction mixture to take advantage of any favorable reactions of mixed aggregates, and addition of LiCl to reaction mixtures of lithium compounds is quite common. In this paper we use computational methods to elucidate the structures and solvation states of lithium carbenoid mixed aggregates with lithium halides and lithium methoxide. In addition, we investigate whether mixed aggregates significantly alter the activation free energy of cyclopropane formation between chloromethyllithium and ethylene. The significance of this is that lithium carbenoids may undergo several types of insertion reactions, or non-insertion reactions like the FBW rearrangement of 1-halovinyllithium carbenoids. The competition between the different types of reactions is likely influenced by mixed aggregates.
Section snippets
Computational methods
All calculations were performed using the Gaussian 98 or Gaussian 03 programs.14 The reported gas phase and solution energies include the electronic and nuclear repulsion energy (Een), thermal corrections to the free energy (including ZPE) at 200 and 298 K, and where applicable, solvation terms. Due to the possibility of several possible conformations of similar energy, it was sometimes necessary to optimize two or more conformations of the same structure and the lowest energy conformer was used
Results and discussion
Because frequency calculations on large systems are often prohibitively expensive, the smaller MIDIX basis set was used to calculate the thermal corrections to the free energies. To be sure that those corrections were reasonable, the geometries of gas phase carbenoid monomers and dimers were optimized with both the MIDIX and 6-31+G(d) basis sets and the thermal corrections calculated, as shown in Table 1. The total thermal correction for the dimerization of the halomethyllithiums is the
Conclusions
Lithium halomethyllithium carbenoids can form mixed aggregates with lithium halides. In the gas phase, mixed trimers and tetramers are formed preferentially over mixed dimers. THF solvation disfavors the formation of the mixed trimers and tetramers, but has only a small effect on the free energy of mixed dimer formation. At temperatures below 200 K, chloromethyllithium, and to a lesser extent, bromomethyllithium mixed dimers will coexist with the free carbenoids. Mixed aggregate formation can
Acknowledgements
This research used resources of the National Energy Research Scientific Computing Center, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC03-76SF00098. This work was also supported by DOE Grant # DE-FG02-02ER25544, and by NSF grant #INT-0454045. Thanks to B. Ramachandran at Louisiana Tech for his lecture notes on which the ‘Derivation of standard state equations’ section of the supplementary materials is based.
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