The Journal of Organic Chemistry
Article
basis set as well as with the M06-2X functional and the aug-cc-pVDZ
basis set.40−42,50 Vibrational frequencies were recomputed with the
latter method, and in this case single-point energies were subsequently
carried out with the maug-cc-pVT(+d)Z basis set.43 Conductor-like
polarized continuum model (CPCM)51,52 B3LYP/6-311+G(d,p) and
M06-2X/aug-cc-pVT(+d)Z single point energies were also computed
to obtain free energies and relative DMSO pKa values at 298 K. These
results were converted to absolute values by using 1,1,1,3,3,3-
hexafluoro-2-propanol as a reference compound and employing its
experimentally measured pKa of 17.9.32
benefit of a rigid versus a flexible catalyst was greatly
diminished, and DMSO pKa values are a better guide to
reactivity than gas-phase acidities.
EXPERIMENTAL SECTION
■
General. Compounds 3(0)−3(3) and 4 were synthesized as
previously described.29,34,48 Molecular sieves (3 Å) were activated at
320 °C overnight and then used to dry solvents over the course of a
few days. DMSO and DMSO-d6 were degassed by carrying out three
freeze−pump−thaw cycles and stored over freshly activated molecular
sieves in a drybox under a nitrogen atmosphere for up to several days
before use. NMR tubes, vials, and flasks were oven-dried and kept in a
drybox along with needles, syringes, and NMR caps. Pentane was dried
over P2O5 at reflux for 1 h and subsequently distilled. Dimsyl
potassium (i.e., KCH2SOCH3) was prepared daily under argon by
reacting DMSO for 45 min with a 30% suspension of potassium
hydride in mineral oil that had been washed 3 times with dry pentane.
A 500 MHz NMR spectrometer was used to record 1H spectra at 295
K.
ASSOCIATED CONTENT
* Supporting Information
■
S
Kinetic data, estimated acidities, and computed geometries and
energies are provided along with the complete citation to ref
49. The Supporting Information is available free of charge on
Acidity Determinations. The acidities of triols 3(0), 3(2), and
3(3) were measured in dry DMSO at 23 °C by 1H NMR as previously
described.36 Multiple measurements were performed for each
compound using one of the following indicators: 1,2,2-triphenyl-
ethanone (pKa = 18.8), 9-carbomethoxyfluorene (pKa = 10.3), or (9-
fluorenyl)triphenylphosphonium bromide (pKa = 6.6).37 Alcohol 3(1)
was examined by carrying out colorimetric titrations with 9-
(phenylthio)fluorene (pKa = 15.4) and 9-(phenylsulfonyl)fluorene
(pKa = 11.5) in both the forward and reverse directions.33 Since the
conjugate bases of these two indicators give colored solutions, it was
possible to determine the favored direction and the relative magnitude
of the equilibrium constant in both instances (i.e., ≤ 1 or ≥1). DMSO
acidity values for additional compounds are provided in the
Supporting Information.
AUTHOR INFORMATION
Corresponding Author
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Generous support from the National Science Foundation, and
the Minnesota Supercomputer Institute for Advanced Compu-
tational Research are gratefully acknowledged.
REFERENCES
■
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mmol) were dissolved in 0.58 mL of the solvent under argon. N-
Methylindole (19 μL, 0.020 g, 0.15 mmol) was syringed into the NMR
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1
tube at 23 °C, and the reaction progress was monitored using the H
NMR signals at 8.04 and 5.23 ppm for the limiting reactant and the
Friedel−Crafts product, respectively. A second-order kinetic ex-
pression (i.e., ln([N-methylindole][β-nitrostyrene]o/[β-nitrostyrene]-
[N-methylin-dole]o) = k([N-methylindole]o − [β-nitrostyrene]o)t)
was used to fit the data and obtain both the rate constants and the first
half-lifes for the disappearance of β-nitrostyrene.
Aminolysis of Styrene Oxide. In a 0.5 dram vial, 23 μL (0.024 g,
0.20 mmol) of styrene oxide, 18 μL (0.018 g, 0.20 mmol) of aniline,
and 5 mol % (0.010 mmol) of the catalyst were mixed together at 60
°C. Reaction progress was qualitatively monitored by TLC (20/80
EtOAc/hexanes) on 250 mm 60 F-254 silica gel plates. At select times
aliquots were withdrawn and dissolved in 0.60 mL of CDCl3, and their
1H NMR spectra were obtained. Reaction progress was determined
using chemical shifts at 2.82 (styrene oxide), 4.52 and 4.95 ppm
(products).
Morita−Baylis−Hillman Transformations. Cyclohexenone (48
μL, 0.048 g, 0.50 mmol), hydrocinnamaldehyde (33 μL, 0.034 g, 0.25
mmol), and 10 mol % (0.025 mmol) of the catalyst were dissolved in
0.25 mL of THF-d8 under argon in a capped NMR tube.
Tributylphosphine (130 μL, 0.11 g, 0.52 mmol) was added via syringe
at room temperature, and the reaction progress was monitored as a
function of time by monitoring the disappearance of the aldehyde
signal at 9.73 ppm and the appearance of the product at 7.04 ppm in
1
the H NMR spectra.
Computations. All of the calculations carried out in this work were
performed at the Minnesota Supercomputer Institute for Advanced
Computational Research using Gaussian 09.49 Full geometry
optimizations and vibrational frequencies were carried out on triols
3(0)−3(3) and their conjugate bases with the B3LYP density
functional and the 6-31+G(d,p) basis set.38,39 The most stable
conformers located were reoptimized with the larger 6-311+G(d,p)
D
J. Org. Chem. XXXX, XXX, XXX−XXX