Organocuprate aggregation and reactivity

A broad range of organocopper intermediates in different
aggregation states were characterized by electrospray ionization
(ESI) mass spectrometry, which provided valuable information on
these fluxional species. To complement the mass spectrometric data,
electrical conductivity measurements and theoretical calculations
were employed. Tetrahydrofuran (THF) solutions of CuCN/(RLi)m
stoichiometry (m = 0.5, 0.8, 1.0, and 2.0 and R = Me, Et, nBu, sBu,
tBu, Ph) were analyzed by ESI mass spectrometry, and organocuprate
anions were detected for all cases. The composition of these
species showed clear dependence on the amount of RLi used. Thus,
while cyanide-free Lin–1CunR2n– anions completely predominated for
CuCN/(RLi)2 solutions, cyanide-containing Lin–1CunRn(CN)n–
complexes prevailed for CuCN/(RLi)m reagents with m ≤ 1. Ligand
mixing studies on LiCuMe2•LiCN and LiCuR2•LiCN systems (R = Et,
nBu, sBu, tBu, Ph) revealed fast exchange equilibria operating in
solution. When THF was substituted for the less polar diethyl ether
(Et2O), no major new species were observed. However, the proportion
of higher nuclearity anions was consistently greater in the latter
solvent than in the former. Further experiments with
2-methyltetrahydrofuran (MeTHF), cyclopentyl methyl ether (CPME)
and methyl tert-butyl ether (MTBE) solutions confirmed the
suggestion that higher aggregation states are favored by lower
polarity solvents. Additional conductivity experiments indicated
that contact ion pairs strongly predominate for solutions in Et2O,
whereas the more polar THF gives rise to larger amounts of
solvent-separated ion pairs. Following the detection of
organocuprate ions, their gas- and condensed-phase reactions were
investigated. Collision-induced dissociation (CID) experiments were
used to study intrinsic reactivities in the gas phase. Higher
aggregates were found to break apart into fragments of lower
nuclearity, whereas monomeric species decomposed by beta-H
elimination when possible. In some CID spectra, the presence of
hydroxyl-containing signals led to the conclusion that a reaction
with background water inside the mass spectrometer was taking
place. This bimolecular reaction was then studied in detail for
many different systems. The results indicate that lithium centers
seem to be a necessary (but not only) pre-requisite for hydrolysis.
For example, no reaction was observed for monomeric CuMe2– anions,
whereas the reactions of LiCu2Me4– and Li2Cu3Me6– were much faster.
Following the successful characterization of organocuprates, their
synthetically useful coupling reactions with alkyl halides were
probed. ESI mass spectrometric experiments, supported by electrical
conductivity measurements, indicated that LiCuMe2•LiCN reacts with
a series of alkyl halides RX (R = Me, Et, nPr, nBu, PhCH2CH2,
CH2=CHCH2, and CF3CH2CH2). The resulting Li+Me2CuR(CN)−
intermediates then afford the observable Me3CuR− tetraalkylcuprate
anions upon Me/CN exchanges with added MeLi. In contrast, the
reactions of LiCuMe2•LiCN with neopentyl iodide and various aryl
halides gave rise to halogen-copper exchanges. Concentration- and
solvent-dependent studies suggested that lithium tetraalkylcuprates
partly form Li+Me3CuR− contact ion pairs and presumably also triple
ions LiMe6Cu2R2−. According to theoretical calculations, these
triple ions consist of two square-planar Me3CuR− subunits binding
to a central Li+ ion. Upon fragmentation in the gas phase, the
Me3CuR− anions undergo reductive elimination, yielding both cross-
(MeR) and homo-coupling products (Me2). The branching between these
channels showed a marked dependence on the nature of R. The
fragmentation of LiMe6Cu2R2− also affords both cross- and
homo-coupling products, but strongly favors the former. This was
rationalized by the preferential interaction of the central Li+ ion
with two Me groups of each Me3CuR− subunit, which thereby block the
homo-coupling channel. Finally, the reactivity of organocuprates in
conjugate addition reactions was investigated, with
cyano-substituted ethylenes C2Hn–4(CN)n, n = 1 – 4 as Michael
acceptors. In the case of acrylonitrile, n = 1, polymerization was
induced, but no reactive intermediates were detected. In contrast,
the reaction with fumaronitrile, n = 2, permitted the detection of
π-complexes in different aggregation states. The identities of the
latter were confirmed by the release of intact fumaronitrile upon
their fragmentation in the gas phase. The reactions with
1,1-dicyanoethylene, n = 2, did not halt at the stage of the
π-complexes, but proceeded all the way to Michael adducts. In the
case of tricyanoethylene, n = 3, dimeric polycyano carbanions were
formed. For tetracyanoethylene, n = 4, the reaction instead leads
to Cu(III) species, which undergo reductive eliminations. Thus, all
intermediates commonly proposed for the conjugate addition of
organocuprates to Michael acceptors were detected, providing strong
evidence for the currently accepted mechanism.