The Journal of Organic Chemistry
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ratio (68% ee) of the cis diastereomer containing 2−3% of the trans
diastereomer was obtained. This was partitioned between 10 mL of 2
M HCl and dichloromethane, and the organic phase was dried with
MgSO4 and concentrated to give 1.140 g (8.03 mmol) of ∼97% cis-
cis/trans stereoisomer, 57% of total), 7.71 (s, cis/trans stereoisomer),
7.69 (s, trans/trans stereoisomer, 28% of total), 2.71 (s, CH3−Ar cis/
cis stereoisomer), 2.68 (s, CH3−Ar cis/trans stereoisomer), 2.66 (s,
CH3−Ar trans/trans stereoisomer), 0.902 (s, t-butyl cis/trans
stereoisomer), 0.901 (s, t-butyl cis/trans stereoisomer), 0.83 (s,
trans/trans), 0.81 (s, cis/cis stereoisomer). 13C NMR (126 MHz,
CDCl3) δ 183.7 (ortho-pyrylium), 183.6 (ortho-pyrylium), 183.5
(ortho-pyrylium), 183.2 (ortho-pyrylium), 175.7 (para-pyrylium),
175.1 (para-pyrylium), 174.2 (para-pyrylium), 123.1 (meta-pyrylium),
122.8 (meta-pyrylium), 121.9 (meta-pyrylium), 121.7 (meta-pyry-
lium), 47.82, 47.81, 47.12, 47.07, 43.8, 43.7, 39.1, 39.0, 32.7, 32.61,
32.57, 31.1, 31.0, 28.5, 28.3, 27.54 (t-butyl), 27.49 (t-butyl), 27.4 (t-
butyl), 26.63, 26.61, 24.2, 24.14, 24.11, 23.71, 23.65. HRMS m/z
(ESI): calcd for C26H43O [M+], 371.3308; found, 371.3310.
Epimerization Experiments. Base Solution Preparation. Stock
solutions of triethylamine, N-methylmorpholine, and pyridine were
prepared by dissolving 10 μL of the amine in 990 μL of the deuterated
solvent, which was chosen for the best NMR resolution (CD3CN for 5
and 7b and CDCl3 for 7a). The concentration of the solutions were
[triethylamine] = 0.072 M, [N-methylmorpholine] = 0.091 M, and
[pyridine] = 0.124 M.
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(+)-2-methylcyclohexanecarboxylic acid. [α]D +3.2 (c 0.7, EtOAc);
lit.22 [α]D −8.0 (c 6.0, EtOH) for (1S,2R).
21
General Procedure for the Preparation of the Acyl
Chlorides. One equivalent of the carboxylic acid and 1.5 equiv of
oxalyl chloride were treated with a catalytic amount (3 μL) of DMF
and stirred for 1 h under nitrogen. Excess oxalyl chloride was then
removed by rotary evaporation, and the product formation was
confirmed by GC−MS. The compound was used without further
purification.
General Procedure for the Preparation of the Pyrylium Salts
7a−b. One equivalent of tert-butanol, 4 equiv of acyl chloride, and 3
equiv of tetrafluoroboric acid diethyl etherate (51−57% HBF4 in
diethyl ether, 7.3 M) were heated at 85 °C for 2 h. The solution turned
deep red. After cooling to room temperature, the reaction mixture was
poured into approximately 40 mL of diethyl ether, precipitating the
pyrylium salt.
2,6-Bis(2-methyl-cyclohexyl)-4-methyl-pyrylium Tetrafluor-
oborate (7a). From 0.17 mL (1.9 mmol) of tert-butanol, 1.270 g (8
mmol) of 2-methylcyclohexanoyl chloride, and 0.8 mL (5.8 mmol) of
tetrafluoroboric acid diethyl etherate (51−57% HBF4 in diethyl ether,
7.3 M), pyrylium 7a was obtained as white powder.
Base-Catalyzed Epimerization Experiments. All of the subsequent
epimerization measurements were performed at 25 °C. The software
package employed to model the data was Corel Quattro Pro 8.0.
Epimerization of 7a with Different Bases. A solution of 0.022 M of
pyrylium 7a in CDCl3 was prepared by dissolving 8 mg (0.022 mmol)
in 990 μL of the solvent in an NMR tube. Base (5 mol %, 0.0011 M)
was added, either 16 μL of the triethylamine stock solution, 12 μL of
the N-methylmorpholine stock solution, or 9 μL of the pyridine stock
Pyrylium 7a from Racemic Starting Material. From 1.270 g (8
mmol) of 2-methylcyclohexanoyl chloride, the pyrylium was obtained
as white powder (0.272 g, 0.73 mmol, 37% yield). mp 127−129 °C.
1H NMR (500 MHz, CDCl3) δ 7.81 (s, (+)-trans/(+)-trans and
1
solution, to the solution, and H NMR was taken at progressive time
(+)-trans/(−)-trans diastereomers 7% of total), 7.79 (s, (+)-cis/
(−)-trans diastereomer 24% of total), 7.77 (s, (+)-cis/(+)-trans
diastereomer 26% of total), 7.74 (s, (+)-cis/(+)-trans diastereomer),
7.73 (s, (+)-cis/(−)-trans diastereomer), 7.70 (s, (+)-cis/(+)-cis
diastereomer 21% of total), 7.68 (s, (+)-cis/(−)-cis diastereomer 22%
of total). 13C NMR (126 MHz, CDCl3) δ 183.5 (ortho-pyrylium),
183.4 (ortho-pyrylium), 183.30 (ortho-pyrylium), 183.27 (ortho-
pyrylium), 183.25 (ortho-pyrylium), 183.2 (ortho-pyrylium), 175.4
(para-pyrylium), 175.3 (para-pyrylium), 174.74 (para-pyrylium),
174.72 (para-pyrylium), 123.2 (meta-pyrylium), 123.03 (meta-
pyrylium), 123.00 (meta-pyrylium), 122.9 (meta-pyrylium), 122.6
(meta-pyrylium), 122.4 (meta-pyrylium), 51.7, 51.6, 46.5, 46.42, 46.37,
46.35, 36.62, 36.59, 36.5, 36.3, 34.7, 34.6, 33.51, 33.50, 33.49, 33.3,
32.6, 32.53, 32.52, 32.50, 32.2, 31.7, 25.66, 25.65, 25.63, 25.54, 25.47,
25.13, 25.11, 25.02, 24.98, 24.19, 24.13, 24.12, 22.3, 22.2, 20.6, 20.1,
19.91, 19.86, 14.0 (CH3), 13.8 (CH3), 13.7 (CH3). HRMS m/z (ESI):
calcd for C20H31O [M+], 287.2369; found, 287.2371.
intervals.
Epimerization of Pyryliums 5, 7a, and 7b with a 5 mol %
Solution of N-Methylmorpholine. A solution of 0.022 M of pyrylium
in deuterated solvent (CD3CN or CDCl3) was prepared by dissolving
8−10 mg (0.022 mmol) in 990 μL of the solvent in an NMR tube.
Then, 5 mol % of base (0.0011 M) was added to the solution, and 1H
NMR was taken at progressive time intervals at 25 °C. For pyrylium 5,
9 mg (0.022 mmol) of pyrylium was dissolved in CD3CN and 13 μL of
the stock solution was added. For pyrylium 7a, 8 mg (0.022 mmol) of
pyrylium was dissolved in CDCl3 and 12 μL of the stock solution was
added. For pyrylium 7b, 10 mg (0.022 mmol) of pyrylium was
dissolved in CD3CN and 12 μL of the stock solution was added.
ASSOCIATED CONTENT
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S
* Supporting Information
Data obtained from the 1H NMR kinetic experiments and from
Pyrylium 7a from Partially Resolved Starting Material. From
1
the mathematical model. H NMR spectra for pyrylium 5 and
1.270 g (8 mmol) of 2-methylcyclohexanoyl chloride, the pyrylium was
1
for pyrylium 5 at equilibrium. H NMR and 13C NMR spectra
1
obtained as white powder (0.250 g, 0.67 mmol, 33% yield). H NMR
for novel compounds pyryliums 7a and 7b. This material is
(500 MHz, CDCl3) δ 7.81 (s, (+)-trans/(+)-trans and (+)-trans/
(−)-trans diastereomers, 4.5% of total), 7.79 (s, (+)-cis/(−)-trans
diastereomer, 14% of total), 7.77 (s, (+)-cis/(+)-trans diastereomer,
30% of total), 7.74 (s, (+)-cis/(+)-trans diastereomer), 7.73 (s,
(+)-cis/(−)-trans diastereomer), 7.70 (s, (+)-cis/(+)-cis diastereomer,
36% of total), 7.68 (s, (+)-cis/(−)-cis diastereomer, 15.5% of total),
0.79 (d, J = 7.0 Hz), 0.78 (d, J = 7.1 Hz), 0.78 (d, J = 7.4 Hz). 13C
NMR (126 MHz, CDCl3) δ 183.4 (ortho-pyrylium), 183.4 (ortho-
pyrylium), 183.3 (ortho-pyrylium), 175.2 (para-pyrylium), 174.6
(para-pyrylium), 123.0 (meta-pyrylium), 123.0 (meta-pyrylium),
122.6 (meta-pyrylium), 122.4 (meta-pyrylium), 51.8, 51.7, 46.6, 46.5,
46.4, 36.7, 36.3, 34.8, 33.5, 33.3, 32.61, 32.55, 32.5, 31.8, 25.7, 25.5,
25.2, 25.1, 25.0, 24.28, 24.25, 24.2, 22.5, 22.3, 22.2, 20.7, 20.1, 19.9,
19.7, 14.0, 13.9 (CH3), 13.8 (CH3), 13.8 (CH3).
AUTHOR INFORMATION
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Corresponding Author
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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We thank the Donors of the American Chemical Society
Petroleum Research Fund (grant no. 47942-AC1) and the
Robert A. Welch Foundation (grant no. AA-1395) for support
of this work, the National Science Foundation (award no.
CHE-0420802) for funding the purchase of our 500 MHz
NMR, Dr. Alejandro Ramirez from the Mass Spectrometry
Center at Baylor University for several analyses, and Katie
Benjamin for all of the editing.
2,6-Bis(4-tert-butyl-cyclohexyl)-4-methyl-pyrylium Tetra-
fluoroborate (7b). From 0.11 mL (1.25 mmol) of tert-butanol,
1.002 g (4.9 mmol) of 4-t-butylcyclohexanoyl chloride, and 0.5 mL
(3.65 mmol) of tetrafluoroboric acid diethyl etherate (51−57% HBF4
in diethyl ether, 7.3 M), compound 7b obtained as white powder
1
(0.241g, 0.53 mmol, 43% yield). mp 212−214 °C. H NMR (500
MHz, CD3CN) δ 7.86 (s, cis/cis stereoisomer 15% of total), 7.81 (s,
11705
dx.doi.org/10.1021/jo401620w | J. Org. Chem. 2013, 78, 11698−11706