Lithium enolates are widely used nucleophiles with a complicated and only partially understood solution chemistry. Deprotonation of 4-fluoroacetophenone in THF with lithium diisopropylamide occurs through direct reaction of the amide dimer to yield a mixed enolate-amide dimer (3), then an enolate homodimer (1-Li)(2), and finally an enolate tetramer (1-Li)(4), the equilibrium structure. Aldol reactions of both the metastable dimer and the stable tetramer of the enolate were investigated. Each reacted directly with the aldehyde to give a mixed enolate-aldolate aggregate, with the dimer only about 20 times as reactive as the tetramer at -120 °C.

Multinuclear NMR spectroscopic studies at low temperature (-110 to -150 degrees C) revealed that lithium p-fluorophenolate and the lithium enolates of cyclohexanone, cyclopentanone and 4-fluoroacetophenone have tetrameric structures in THF/Et(2)O and THF/Et(2)O-HMPA by study of the effects of the addition of HMPA. The Z and E isomers of the lithium enolate of 1,3-bis-(4-fluorophenyl)-2-propanone (5F-Li) show divergent behavior. The Z isomer is completely dimeric in pure diethyl ether, and mostly dimeric in 3:2 THF/ether, where monomer could be detected in small amounts. TMTAN and PMDTA convert Z-5F-Li to a monomeric amine complex, and HMPA converts it partially to monomers, and partially to lithiate species (RO)(2)Li(-) and (RO)(3)Li(2-). Better characterized solutions of these lithiates were prepared by addition of phosphazenium enolates (using P4-(t)Bu base) to the lithium enolate in 1:1 ratio to form triple ion (RO)(2)Li(-) P4H(+), or 2:1 ratio to form the higher lithiate (RO)(3)Li(2-) (P4H(+))(2)) (quadruple ions). The E isomer of 5F-Li is also dimeric in 3:2 THF/Et(2)O solution, but is not detectably converted to monomer either by PMDTA or HMPA. In contrast to Z-5F-Li, the E isomer is tetrameric in diethyl ether even in the presence of excess HMPA. Thus for the two isomers of 5F six different enolate structures were characterized: tetramer, dimer, CIP-monomer, SIP-monomer, triple ion, and quadruple ion.

Strategies for teaching NMR spectral interpretation in the undergraduate organic chemistry curriculum are often faculty-centered and can lead to student reliance on rote memorization and "guess and check" methods rather than critical-thinking skills for structure determination. This article describes a student-focused methodology for the introduction of NMR spectral interpretation. Guided-inquiry tutorials using NMR prediction tools were developed to enable students to investigate the trends and concepts in 13 C and 1 H NMR spectral interpretation, with an emphasis on making connections between data and foundational chemical knowledge. A systematic approach to solving unknown structure problems is presented, providing a framework for students to organize spectral data and to build molecules from partial structures. The success of this NMR spectroscopy teaching strategy, which can be adapted for either laboratory or lecture environments, was demonstrated both in positive student survey responses as well as in quantitative data showing a significant improvement in exam question scores.

A variety of multinuclear NMR techniques, in combination with X-ray diffraction methods, were used to probe the solution structure of α-aryl lithium enolates of bis(4-fluorobenzyl) ketone (1-H), phenyl 4-fluorobenzyl ketone (2-H), and N,N-dimethyl 4-fluorophenylacetamide (3-H) in ethereal solvents and in the presence of cosolvent additives PMDTA, TMTAN, HMPA, and cryptand [2.1.1]. All three enolates were dimers in THF solution, and were converted to monomers by the triamine additives, PMDTA and TMTAN. The exchange of the triamine-solvated monomers with their ethereal-solvated dimer counterparts was probed by using dynamic NMR (DNMR). The cosolvent HMPA formed monomers along with minor amounts of lithiate species, (RO)(2)Li(-) and (RO)(3)Li(2-), which were also observed when cryptand [2.1.1] was used as a cosolvent, or when mixed lithium-phosphazenium enolate solutions were prepared. Dynamic exchange of lithiate species was investigated by DNMR spectroscopy. The barrier to rotation of the conjugated 4-fluorophenyl ring of these diverse enolate structures was measured and found to be consistent with a resonance picture where lower aggregation states lead to increased delocalization of negative charge. The lithium enolate aggregates identified were compared to the "naked" α-4-fluorophenyl enolates generated with the phosphazene base P4. The barrier to aryl ring rotation was 2.7 kcal/mol higher for the phosphazenium enolate 3-Li·P4H compared to the dimer (3-Li)(2). Structural characterization of a phosphazenium enolate through X-ray crystallography was obtained for the first time. Additional aspects of the Schwesinger base P4 were investigated which included characterization of the solution exchange behavior of the protonated and unprotonated forms as well as determination of the solid state structure by X-ray diffraction.

Solution properties of enolates generated using the phosphazene (Schwesinger) base P4-tBu were investigated by NMR spectroscopy. With a full equivalent of base the benzyl ketones 1a and 1b, the acetophenone 2, the arylacetaldehyde 1c, and the methyl arylacetate 1d formed the expected "naked" (P4H+) enolates 3 and 7. However, at a half-equivalent of base the ketones 1a and 1b as well as the aldehyde 1c formed solutions of stable hydrogen-bonded dimeric (enol-enolate) structures (4). The acetophenone 2, on the other hand, forms only traces of the H-bonded dimer 8 during deprotonation of 2. The thermodynamic product was the isomeric self-aldol condensation product 12. The mechanism of this condensation was elucidated by low temperature rapid-injection (RI) NMR spectroscopy. Solutions of 8 stable enough for NMR characterization could be transiently generated by semiprotonation of the enolate 7 with HCl.OEt2 at -130 degrees C using RINMR. The ester enolate 1d gave no trace of 4d even on a time scale as short as a few seconds at -130 degrees C either during the semideprotonation of 1d, or during semiprotonation of the enolate 3d. Long-lived solutions of the enols derived from 1a, 1b, 1c, and 2 (but not 1d) could be produced by full protonation of the phosphazene enolates with HCl.OEt2 at low temperature.