Nonradical Pathway in the Photoracemization of Aryl Sulfoxides
A R T I C L E S
mixture was cooled to 0 °C, n-BuLi (1.78 M in hexane, 0.42 mL, 0.76
mmol) was added with stirring over 20 min. The mixture was then
cooled to -78 °C. (R)-Neopentyl p-tolyl sulfoxide (0.10 g, 0.48 mmol)
in 1 mL of THF was then added to the cold reaction mixture over 5
min. After an additional 5 min, the reaction was quenched with excess
D2O (2 mL). Ether (20 mL) and water (20 mL) were added and the
organic layer was separated. The ether layer was washed with brine
and dried (MgSO4) and solvent was removed. The crude product was
recrystallized three times from ethanol to obtain 30 mg (30%) of highly
purified material, which was a mixture of 94% (RS,SC), 5% (RS,RC),
and 1% (SS,SC) isomers. No sulfoxide containing two R-protons was
observed by NMR. The peaks at 2.81 and 2.52 ppm changed from
13.5 Hz doublets to 2 Hz triplets (deuterium coupling).
radical to form sulfoxides over sulfenic esters despite a much
lower selectivity for the benzyl radical, and (d) the selective
rotation of the p-Tol-SO• bond over the Me3C-CHD• bond in
the geminate radical pair. We do not find this combination of
requirements credible and conclude that photochemical stereo-
mutation of sulfoxides is accomplished both by R-cleavage and
by a noncleavage pathway, which we believe derives from
geometric relaxation in an electronically excited state.
Experimental Section
General Methods. Commercially available compounds were used
without purification except as noted. THF was distilled under Ar from
the sodium benzophenone ketyl and diisopropylamine was distilled from
CaH2. NMR spectra were obtained on either a Varian VXR-300 or a
Bruker Avance DXR 400. HPLC data were collected using a HP 1050
instrument equipped with a diode array UV/vis detector and an Astec
Chirobiotic V (Vancomycin stationary phase) column. Mass spectra
were collected on a VG Magnum ion trap GC-MS operating in EI mode.
The NMR chiral shift reagent of choice was (R)-(-)-N-(3,5-
dinitrobenzoyl) R-phenylethylamine34 in CDCl3. Best results were
obtained when the shift reagent was near 100 mM, given a sulfoxide
concentration of ca. 1 mM. Several other conditions were evaluated
and found inferior, including use of other solvents and use of
R-methoxyphenylacetic acid35 as a shift reagent. Spectra for analysis
were obtained at 400 MHz with deuterium decoupling.
The relative chemical shifts of the C1-protons of the RS and SS
isomers in the presence of the shift reagent were determined from a
sample of nondeuterated neopentyl tolyl sulfoxide that was of a known
RS:SS ratio of about 90:10. The resonance is slightly downfield for the
RS isomers. The absolute stereochemistry at the sulfur center was
determined from the sense of the CD spectrum.31
Photolyses for NMR Analysis. A solution of 1 (340 µM) in CH3CN
(100 mL) was prepared in a septum-sealed quartz tube equipped with
a stir bar. The solution was purged with Ar to remove O2. It was
irradiated at 254 nm using a low-pressure Hg lamp in a Rayonet
minireactor equipped with a magnetic stirrer and a fan. Only a 15 mm
gap of a single 4 W bulb was not covered with foil in order to slow
the reaction. At 2 min intervals, about 25 mL of the solution was
removed by syringe. No photoproducts aside from stereoisomers of
1 were observed by HPLC or NMR. The solvent was evaporated, and
the residue was dissolved in CDCl3 such that the concentration was
about 1 mM. The samples were split into two NMR tubes and then
analyzed. Spectra were obtained after adding successive 200 µL aliquots
of saturated (e200 mM) shift reagent in CDCl3. Typically, 256 scans
were obtained. The S/N ratio in Figure 1 is limited by the low
concentration of the (RS,RC) and (SS,SC) isomers (ca. 10-4 M) in
the presence of approximately 10-1 M shift reagent. The ratio of
[(RS,RC)-1 + (SS,SC)-1] to [(RS,SC)-1 + (SS,RC)-1] was determined by
ordinary integration of the 2.81 and 2.52 ppm peaks, and the ratios of
(RS,RC)-1 to (SS,SC)-1 were obtained using the line shape analysis
feature of WinNMR. The error bars in Figure 2 are best-estimate error
limits, based on estimates of systematic error and reproducibility of
the three measurements. The HPLC measurements do not contribute
significantly to the error.
(R)-Neopentyl p-Tolyl Sulfoxide.36 The procedure of Rieke37 was
used to generate the organometallic reagent. MgCl2 (2.75 g, 29.1 mmol),
KI (2.07 g, 53.0 mmol), and K (2.23 g, 13.2 mmol) were placed in a
flame-dried 250 mL round-bottom flask equipped with a condenser
and stir bar under argon. THF (70 mL) was added and the mixture
was held at reflux for 2 h, then at room temperature for 30 min.
Neopentyl bromide (1.67 mL, 13.2 mmol) was added and the system
was brought to reflux again for 20 min with vigorous stirring.
(1R,2S,5R)-(-)-Menthyl (S)-p-toluenesulfinate38 (3.18 g, 10.8 mmol)
in THF (10 mL) was added at room temperature and the system was
brought to reflux. After 4 h, the system was cooled, quenched with
saturated NH4Cl(aq), and extracted with ether. The organic layer was
washed with brine, dried (MgSO4), and concentrated. Purification by
flash chromatography (silica, 5% EtOAc in CH2Cl2) gave 0.50 g of
sulfoxide (22%). Typical enantiomeric ratios after initial workup were
95:5. Multiple recrystallizations from hexane gave samples with >99%
1
of the (R)-sulfoxide. H NMR (CDCl3) δ 1.20 (s, 9H); 2.42 (s, 3H);
Quantum Yields. Duplicate 4.0 mL solutions of (R)-neopentyl
p-tolyl sulfoxide (5 mM) in acetonitrile contained in 1 cm square
fluorescence cells were degassed by purging with Ar. Excitation was
provided by a 75 W Xe lamp filtered through a monochromator set to
254 nm with (12 nm linear dispersion. The stirred sample was held
in a fixed sample holder mounted at the monochromator exit, which
ensures complete absorption of the exiting light. Samples of a few
microliters each were periodically removed and analyzed by chiral
HPLC. Conversion from the RS isomers to SS isomers was linear with
time up to at least 10% conversion. The photon flux was determined
by azoxybenzene actinometry.
2.52 (d, J ) 13.5 Hz, 1H); 2.81 (d, J ) 13.5 Hz, 1H); 7.33 (d, J ) 8
Hz, 2H); 7.52 (d, J ) 8 Hz, 2H). 13C NMR (CDCl3) δ 142.6, 141.3,
130.1, 124.0, 74.1, 32.1, 30.0, 21.6. UV-vis (λmax 248.2 nm). Ion trap
MS m/e (relative abundance) 211 (M + 1, 100), 194 (10), 140 (38),
92 (14). HPLC (90:10, MTBE:acetonitrile, 1 mL/min) retention times
were 18.4 and 19.7 min for (S) and (R) sulfoxides, respectively. Racemic
sulfoxide was obtained by m-CPBA oxidation (1 equiv, -78 °C,
CH2Cl2) of the neopentyl tolyl sulfide, obtained from sodium p-toluene-
thiolate and neopentyl tosylate.39
(RS,SC)-1-Deuterio-2,2-dimethylpropyl p-Tolyl Sulfoxide (1). Di-
isopropylamine (0.11 mL, 0.81 mmol) and THF (10 mL) were charged
to a flame-dried 25 mL flask equipped with an argon inlet. After the
Acknowledgment. This work is dedicated to Professor
Ronald Breslow, on the occasion of whose 70th birthday
celebration its essential results were first discussed. We grate-
fully acknowledge financial support from the Research Corpora-
tion and the National Science Foundation and thank Professor
James Espenson for help with the kinetic simulations.
(34) Deshmukh, M.; Dun˜ach, E.; Juge, S.; Kagan, H. B. Tetrahedron Lett. 1984,
25, 3467-70.
(35) Buist, P. H.; Marecak, D.; Lolland, H. L.; Brown, F. M. Tetrahedron:
Asymmetry 1995, 6, 7-10.
(36) Rayner, D. R.; Gordon, A. J.; Mislow, K. J. Am. Chem. Soc. 1968, 90,
4854-60.
(37) Rieke, R. D.; Bales, S. E. J. Am. Chem. Soc. 1974, 96, 1775-81.
(38) Klunder, J. M.; Sharpless, K. B. J. Org. Chem. 1987, 52, 2598-602.
(39) Parham, W. E.; Edwards, L. D. J. Org. Chem. 1968, 33, 4150-4.
JA017228M
9
J. AM. CHEM. SOC. VOL. 124, NO. 11, 2002 2547