The reaction of equimolar diethylzinc with a carboxylic acid releases one equivalent of ethane and gives the mixed organozinc species 'ethylzinc carboxylate', EtZnO2CR (R = Me, CF3, Ph). In 1974, Inoue, Kobayashi and Tozuka reported that the ethyl-zinc bond in these carboxylates is protonolyzed by active-hydrogen compounds such as methanol and pyrrole faster than an ethyl group of diethylzinc itself, whereas the corresponding ethylzinc alkoxide, phenoxide and thiophenoxide derivatives react far more slowly; they attributed the enhancement to increased Lewis acidity of the carboxylate-bound zinc (stronger coordination of the proton donor) rather than to increased intrinsic nucleophilicity of the Zn-C bond. The study, however, reported no quantitative kinetics, identified no zinc-bound substrate complexes, and characterized the reacting solutions only by cryoscopic association numbers. Later work (2005-2015) has determined the solid-state and solution structures and the solvent-dependent speciation (the identity and proportions of the molecular species actually present in solution) of ethylzinc acetate, benzoate, fluorocarboxylate and related derivatives, including disproportionation equilibria that release free diethylzinc. What remains open is the quantitative kinetic and mechanistic core of the 1974 observation: rate laws, reaction orders and activation parameters for protonolysis of ethylzinc carboxylates by protic donors under speciation-controlled conditions, and a direct experimental or computational discrimination between Lewis-acid/coordination activation and Zn-C bond-polarity control, together with the solvent, temperature and substituent generality of the effect.

Background

Organozinc compounds carry a carbon-zinc bond and are the mildest of the commonly used main-group organometallic reagents. The parent reagent here is diethylzinc, Et2Zn, a linear, two-coordinate and pyrophoric liquid (it ignites spontaneously on contact with air): its zinc center is Lewis acidic (an electron-pair acceptor), while the Zn-C bond is only weakly nucleophilic compared with organolithium or Grignard reagents, so reactions of the ethyl group often require the reaction partner first to coordinate to zinc. Protonolysis is the exchange of a metal alkyl for a proton, Et-Zn + H-X -> Zn-X + ethane, and 'active hydrogen compounds' are O-H and N-H donors (alcohols, phenols, N-heterocycles such as pyrrole) acidic enough to cleave the metal-carbon bond. Earlier work summarized in the source study had established that methanol protonolyzes diethylzinc in two steps, the first ethyl group being displaced rapidly and the second much more slowly, and that the isolated ethylzinc alkoxides exist as associated oligomers in solution, so both the ancillary ligand X on EtZnX and the aggregation state were known to govern reactivity.

In 1974 Inoue, Kobayashi and Tozuka showed that the equimolar reaction of diethylzinc with acetic, trifluoroacetic or benzoic acid is rapid and quantitative, liberating one equivalent of ethane and giving the 'ethylzinc carboxylate' EtZnO2CR with no free diethylzinc detectable by infrared or NMR spectroscopy. Cryoscopy (freezing-point-depression molecular-weight measurement) in benzene at 0.1 M gave degrees of association (the average number of EtZnX formula units combined per dissolved molecule) of 0.96 for diethylzinc but 3.9 (acetate), 2.9 (benzoate), 3.3 (trifluoroacetate) and 4.2 (methoxide), so the carboxylates exist as associated aggregates whose detailed architecture and stoichiometry were not determined. In initial-rate experiments (comparing rates at the very start of reaction) in toluene at 0 C, the ethyl groups of all three ethylzinc carboxylates were protonolyzed by methanol faster than those of diethylzinc, whereas ethylzinc methoxide, phenoxide and thiophenoxide reacted much more slowly. Pyrrole, of nearly the same acidity as methanol (pKa 16.5 versus 16.6), reacted far more slowly than methanol, which the authors attributed to pyrrole's weaker ability to coordinate the zinc center. They therefore proposed that the carboxylate ligand, being electron withdrawing, raises the Lewis acidity of zinc and accelerates proton transfer by binding the proton donor, rather than increasing the intrinsic nucleophilicity of the Zn-C bond. This mechanistic dichotomy, Lewis-acid activation by substrate coordination versus Zn-C bond-polarity control, was however supported only by relative initial rates. The study contained no rate constants, reaction orders or activation parameters, and no spectroscopic evidence for a zinc-bound substrate complex, so the mechanistic proposal remained an untested hypothesis.

Between 2005 and 2015 the structural side was transformed: single-crystal X-ray diffraction and solution NMR methods, including DOSY (diffusion-ordered spectroscopy, which separates NMR signals by molecular size through measured diffusion coefficients), established that ethylzinc acetate is a pentanuclear cluster (a single molecule containing five zinc atoms), [Zn5(OAc)6(Et)4], in benzene or toluene but dimeric [EtZn(OAc)]2 in tetrahydrofuran, that ethylzinc benzoate forms a hexanuclear barrel, that organozinc fluorocarboxylates form polymeric chains, and that a bulky m-terphenyl carboxylate exists in a room-temperature equilibrium, 3 EtZnO2CR -> [Zn2(O2CR)3Et(THF)] + Et2Zn, i.e. exactly the disproportionation-type equilibrium between mixed species and free diethylzinc that the 1974 work could not exclude. The structural prerequisite for a mechanistic study of the 1974 reactivity question is thus now in place; the quantitative kinetic and mechanistic account itself is still missing.

Problem Statement

Determine, quantitatively and mechanistically, the protonolysis of the ethyl-zinc group in ethylzinc carboxylates by active-hydrogen compounds and the origin of its enhancement relative to diethylzinc. The three objectives below are jointly posed; each is to be pursued under conditions in which the solution speciation of the reacting aggregates is established or controlled (using the now-known structures and their solvent- and temperature-dependent equilibria), against the diethylzinc control. The minimum scope is the source set of carboxylates R = Me, CF3, Ph (justified extensions permitted) and the donor pair methanol (O-H) and pyrrole (N-H).

  1. Measure the kinetics of protonolysis of EtZnO2CR by O-H donors such as methanol and N-H donors such as pyrrole against the diethylzinc control, obtaining the rate law, reaction orders, rate constants, and activation parameters from variable-temperature measurements, and confirm that this rate law, together with the measured rates, accounts for the qualitative ordering documented by the source study: the ethyl groups of ethylzinc acetate, trifluoroacetate and benzoate are protonolyzed by methanol faster than those of diethylzinc itself.
  2. Establish whether the carboxylate-induced rate enhancement arises from enhanced Lewis-acidic coordination of the proton donor at zinc or from an increased intrinsic polarity or nucleophilicity of the Zn-C bond.
  3. Establish the solvent and temperature dependence of the protonolysis kinetics and the generality of the substituent effect across carboxylates and proton donors.

References

  1. Shohei Inoue, Makoto Kobayashi, Takashi Tozuka, 'High reactivity of the ethyl—zinc group “ethylzinc carboxylate” towards acitive hydrogen compounds', Journal of Organometallic Chemistry 81 (1974) 17-21. DOI: 10.1016/S0022-328X(00)87881-X, https://doi.org/10.1016/S0022-328X(00)87881-X
  2. Piotr Górecki, Witold Kuran, 'Kinetics and mechanism of the reactions of diethylzinc with phenols in cyclic ethers', Journal of Organometallic Chemistry 265 (1984) 1-7. DOI: 10.1016/0022-328X(84)80045-5, https://doi.org/10.1016/0022-328X(84)80045-5
  3. Diane A. Dickie, Michael C. Jennings, Hilary A. Jenkins, Jason A. C. Clyburne, 'A Zinc Carboxylate Network Containing Metal Sites with Low Coordination Numbers', Inorganic Chemistry 44 (2005) 828-830. DOI: 10.1021/ic048443h, https://doi.org/10.1021/ic048443h
  4. Janusz Lewiński, Wojciech Bury, Michał Dutkiewicz, Michał Maurin, Iwona Justyniak, Janusz Lipkowski, 'Alkylzinc Carboxylates as Efficient Precursors for Zinc Oxocarboxylates and Sulfidocarboxylates', Angewandte Chemie International Edition 47 (2008) 573-576. DOI: 10.1002/anie.200703125, https://doi.org/10.1002/anie.200703125
  5. Katherine L. Orchard, Andrew J. P. White, Milo S. P. Shaffer, Charlotte K. Williams, 'Pentanuclear Complexes for a Series of Alkylzinc Carboxylates', Organometallics 28 (2009) 5828-5832. DOI: 10.1021/om900683z, https://doi.org/10.1021/om900683z
  6. Katherine L. Orchard, Jonathan E. Harris, Andrew J. P. White, Milo S. P. Shaffer, Charlotte K. Williams, 'Solvent Dependence of the Structure of Ethylzinc Acetate and Its Application in CO2/Epoxide Copolymerization', Organometallics 30 (2011) 2223-2229. DOI: 10.1021/om200004a, https://doi.org/10.1021/om200004a
  7. A. L. Johnson, A. J. Kingsley, G. Kociok-Köhn, K. C. Molloy, A. L. Sudlow, 'Inorganic and Organozinc Fluorocarboxylates: Synthesis, Structure and Materials Chemistry', Inorganic Chemistry 52 (2013) 5515-5526. DOI: 10.1021/ic400420h, https://doi.org/10.1021/ic400420h
  8. Mikael A. Minier, Stephen J. Lippard, 'Conversion between Doubly and Triply Carboxylate Bridged Bis(ethylzinc) Complexes and Formation of the (mu-Oxo)tetrazinc Carboxylate [Zn4O(ArTolCO2)6]', Organometallics 33 (2014) 1462-1466. DOI: 10.1021/om5000503, https://doi.org/10.1021/om5000503
  9. Agnieszka Grala, Małgorzata Wolska-Pietkiewicz, Anna Wojewódzka, Monika Dabergut, Iwona Justyniak, Janusz Lewiński, 'Structural Diversity of Ethylzinc Carboxylates', Organometallics 34 (2015) 4959-4964. DOI: 10.1021/acs.organomet.5b00557, https://doi.org/10.1021/acs.organomet.5b00557
  10. E. A. B. Kantchev, M. G. Organ, 'Protonolysis of Alkyl Derivatives of Metals from Groups 3, 4, 12, and 13 (Including Lanthanides and Actinides, Excluding Boron)', Science of Synthesis, Alkanes volume (2009). DOI: 10.1055/sos-sd-048-00007, https://doi.org/10.1055/sos-sd-048-00007 (review chapter covering zinc)