Aggregation and ReactiVity of Phenyllithium Solutions
J. Am. Chem. Soc., Vol. 120, No. 29, 1998 7209
be fragmentation of the disulfide radical anion to R-S- and
R’-S‚. The intervention of SIPs in reactions of PhLi with
substrates is also indicated by other effects. For example, PhLi/
HMPA reacts with all enolizable ketones to give only enolization
and no carbonyl addition.
Probe temperatures were measured using a platinum resistance
thermometer or a thermocouple before and after the acquisition of each
spectrum and varied by less than 1 °C between each of the two
measurements. Twenty minutes were allowed between acquisitions
for the temperature to equilibrate.
Referencing NMR Spectra. 13C chemical shifts are reported in
Summary. The aggregation state of PhLi in ethereal solvents
has been determined previously by indirect methods. We have
reported the first observation of fully resolved ipso carbon
signals for all of the PhLi aggregates to firmly establish the
tetramer and dimer structures in ether and the dimer and
monomer structures in THF. Furthermore, the effects of adding
polar additives, such as 2,5-dimethyltetrahydrofuran, THF,
dioxolane, DME, TMEDA, PMDTA, HMTTA, HMPA, DMPU,
and 12-crown-4, to PhLi solutions in THF and/or ether have
6
7
ppm relative to internal C6H6 (δ 129.0). Both Li and Li chemical
shifts are referenced to external 0.30 M LiCl/methanol standard (δ 0.0)
at -100 °C. 31P chemical shifts are reported relative to external 0.1
M PPh3 in THF (δ -6.0) at -100 °C.
Product Analysis. GC analyses were performed on a Varian 3700
analytical GC with a flame ionization detector and a 12 m × 0.32 mm
3*12QC3/SE-30 capillary column (He pressure of 6.0 psi, column
flow rate (split ratio 300:1) of 3 mL/min and column temperature: 85
°C for 4 min, increased at 20 °C/min to 145 °C, after 2 min at 145 °C,
returned to 85 °C). Retention times and response factors (Rf) with
respect to n-undecane are as follows: thioanisole: 3.1 min, 1.65;
n-undecane: 4.0 min, 1.00; 2,5-(dimethylthio)furan: 7.20 min, 2.40;
2-methylthio-3-(methyl)thiophene: 7.7 min, 2.20; 2-methylthio-4-
(methyl)thiophene: 8.3 min, 2.20. Rf’s are defined for a 1:1 molar
solution of n-undecane to compound, where Rf ) (peak area n-
undecane)/(peak area compound).
6
been studied by low-temperature NMR techniques (13C, Li,
7Li, and 31P). We have described in detail the rich number of
structures that PhLi forms when complexed to these polar
additives. In addition, the reactivities of these PhLi solutions
were measured by determining the rate and regioselectivity of
metalation of substituted furans and thiophenes, resulting in the
following trend for enhancing PhLi reactivity: HMPA > 12-
crown-4 > PMDTA > HMTTA > TMEDA.
Typical Procedure for an NMR Study of PhLi in THF, Ether,
and/or Dimethyl Ether with the Addition of Cosolvents. An oven
dried 10 mm NMR tube was fitted with a 9 mm i.d. rubber septum
and flushed with N2 until the tube was cool. The rubber septum was
wrapped with Parafilm, the tube was cooled to -78 °C with positive
N2 pressure, and ∼3.6 mL total volume of THF, ether, and/or dimethyl
ether was added. The desired amount (∼0.4 mL) of PhLi stock solution
in THF or ether was slowly added, the tube was shaken briefly, and
the septum was sealed with grease. Before the experiment was begun,
the shim values were checked and adjusted for CDCl3. The instrument
was unlocked, and the sweep was turned off. The NMR probe was
cooled to below -100 °C, and the sample was inserted into the probe.
After 10 min, optimization of the FID of C-3 of THF or C-1 of ether
was done. Both 13C and 6/7Li NMR spectra were acquired. The sample
was removed and stored at -78 °C. The grease from the septum top
was removed, a desired amount of cosolvent was added, and the top
of the septum was greased. The NMR tube was placed in the probe
and after 10 min, both 13C and 6/7Li NMR spectra were acquired. This
process was repeated for additional equiv of cosolvent.
Experimental Section17
General. All glassware was dried in a 110 °C oven overnight or
flame dried and flushed with N2 to remove air and moisture. All
reactions were performed under an atmosphere of dry N2.
Solvents and Materials. Tetrahydrofuran (THF) and diethyl ether
(ether) were freshly distilled from sodium benzophenone ketyl prior
to use. Dimethyl ether (bp -24.9 °C) was first condensed into THF/
sodium benzophenone ketyl solution at -78 °C and subsequently
distilled through a cannula into a collection vessel cooled to -78 °C.
HMPA was distilled at reduced pressure (0.7 mm, 84-88 °C) from
CaH2 and stored over molecular sieves. TMEDA, PMDTA, HMTTA,
and 12-crown-4 were distilled at reduced pressure from Na metal and
stored over molecular sieves (TMEDA: 40 mm, 24-29 °C; PMDTA:
6.0 mm, 58-62 °C; HMTTA: 0.01 mm, 82-85 °C; 12-Crown-4: 6.5
mm, 65-68 °C). All compounds were commercially available, except
for methyl isopropyl disulfide27 and HMTTA28 which were prepared
according to literature procedures.
Salt-free PhLi (reaction of PhI with n-BuLi)1g,29 and n-butyllithium-
6Li (reaction of n-BuCl with 6Li metal)1g,6a were also prepared according
to literature procedures. 6Li metal (95.5%) was purchased from Oak
Ridge National Lab. Solutions of lithium reagents in ether and THF
were titrated against n-propanol with 1,10-phenanthroline as indicator30
or quenched with dimethyl disulfide and analyzed by GC.
Standardization of PhLi Solution for Kinetic Studies. A 50 mL
24/40 Erlenmeyer flask was dried, equipped with a septum, and purged
with N2. To the flask was added 1.5 M PhLi in THF (20 mL, 30 mmol),
and then the solution diluted with 10 mL of THF. To the solution was
added n-undecane (0.634 mL, 3.0 mmol) to be used as a GC standard.
A 1.0 mL aliquot of the resulting solution was syringed into each of
three dry, purged 5 mL round-bottomed flasks equipped with septa
and stir bars. Each was quenched with 100 µL of MeSSMe (1.1 mmol).
Saturated NH4Cl solution (∼0.10 mL) was added to each flask, causing
a white precipitate, and the solutions were dried over Na2SO4. Analysis
by capillary GC gave the concentrations of PhLi and n-undecane to be
0.90 and 0.11 M, respectively.
NMR Spectroscopy. All low-temperature multinuclear NMR
experiments were conducted on a Bruker AM-360 spectrometer
equipped with a 10 mm wide-bore broadband probe tuned at 90.556
MHz (13C), 52.984 MHz (6Li), 139.905 MHz (7Li), or 145.785 MHz
(31P). All spectra were acquired in a combination of the protio solvents
THF, ether, and/or dimethyl ether with the spectrometer unlocked. The
Typical Procedure To Study the Effect of Donor Additives on
the Reactivity of PhLi. Six long-necked 5 mL round-bottom flasks
were dried, equipped with septa and stir bars, and purged with N2.
THF and the desired amount of cosolvent were added to give a total
solvent volume of 2.1 mL. The solutions were cooled to -78 °C while
keeping positive N2 pressure in each flask. Stock PhLi in THF solution
(0.90 M, 0.33 mL, 0.30 mmol; 0.11 M n-undecane, 0.0363 mmol) was
added down the side of each flask, and the solutions were mixed
thoroughly. After 10 min at -78 °C, 1 equiv of substrate (0.30 mmol)
was added using a microsyringe. After stirring at -78 °C for a given
time, each solution was quenched with 100 µL of MeSSMe (1.1 mmol).
The cold bath was removed, and the flasks were allowed to warm to
room temperature while stirring. Saturated NH4Cl solution (0.2 mL)
and pentane (0.5 mL) were added to each, and the solutions were dried
over Na2SO4. Subsequent analysis by capillary GC was done to
determine the concentrations of unreacted PhLi and reacted substrate.
6
digital resolution was 0.6-1.2 Hz for 13C, 0.2-0.8 Hz for Li, 0.5-
1.0 Hz for 7Li, and 0.6-1.2 Hz for 31P. (Note: Although the
spectrometer was unlocked during acquisition, the field was generally
very stable, and only occasionally did a spectrum have to be retaken
due to a field shift.)
Lorenzian multiplication (LB) was applied to 13C spectra. Gaussian
7
multiplication was applied to Li and 31P spectra, where the Gaussian
broadening (GB) was equal to the duration of the free induction decay
and the Lorenzian broadening (LB) was set to -(digital resolution/GB).
6Li spectra were not enhanced.
(27) Alonso, M. E.; Aragona, H.; Chitty, A. W.; Compagnone, R.; Mart´ın,
G. J. Org. Chem. 1978, 43, 4491.
(28) Marxer, A.; Miescher, K. HelV. Chim. Acta 1951, 34, 924.
(29) Schlosser, M.; Ladenberger, V. J. Organomet. Chem. 1967, 8, 193.
(30) Watson, S. C.; Eastham, J. F. J. Organomet. Chem. 1967, 9, 165.