596 J . Org. Chem., Vol. 66, No. 2, 2001
Marzinzik and Sharpless
131.70; HRMS (FAB+) calcd for C14H17Cl2NO2S2Na+ (M +
Na+): 387.9975, found: 387.9986.
Sch em e 2
9-Th ia b icyclo[3.3.1]n on a n e-N-p h en ylsu lfon ysu lfili-
m in e (7b): yield after recrystallization from AcOH/H2O, mp
118 °C: 739 mg (95%), white crystals; 1H NMR (400 MHz,
CDCl3): δ ) 1.66 (m, 4H), 2.00 (m, 2H), 2.15 (m, 4H), 2.83 (m,
2H), 2.98 s, 2H), 7.42 (m, 3H), 7.90 (m, 2H); 13C NMR (125
MHz, CDCl3): δ 19.76, 20.18, 29.75, 46.13, 126.14, 128.62,
131.06; HRMS (FAB+) calcd for C14H19NO2S2Na+ (M + Na+):
320.0755, found: 320.0752.
2,6-Dich lor o-9-th iabycyclo[3.3.1]n on an e-N-(2-n itr oph en -
yl)su lfon ylsu lfilim in e (7c): yield after recrystallization from
AcOH/H2O: 953 mg (93%), white crystals, mp 230 °C; 1H NMR
(400 MHz, CDCl3): δ ) 2.18 (m, 6H), 2.44 (m, 1H), 2.75 (m,
1H), 3.41 (s, 2H), 4.50 (m, 1H), 5.07 (m, 1H), 7.61 (m, 2H),
8.14 (m, 2H); 13C NMR (125 MHz, CDCl3): δ ) 17.86, 22.42,
30.06, 30.39, 49.53, 51.94, 52.91, 55.59, 123.85, 130.43, 132.05,
132.58; HRMS (FAB+) calcd for C14H16Cl2N2NaO4S2Na+ (M +
Na+): 432.9826, found: 432.9818.
10 and syn-10 in a 9:1 ratio, whereas when t-BuOCl and
TsNH- were used, syn-10 was noted as the major
isomer.17 With the expectation that the new process
would give the same stereochemistry as the “traditional
procedure”, 2-methylthiane (9) was treated with 5 in
acetonitrile for 16 h and yielded a 9:1 mixture of anti-
and syn-10 in 75% yield. The complete absence of
sulfoxide byproducts in this system, taken together with
the anti-stereochemistry established by Kucsman et al.17
are the key facts constraining mechanistic proposals for
this transformation. The absence of sulfoxides and the
observed anti preference are both consistent with the
direct transfer of TsN to the least-hindered face of the
sulfide in the rate-determining step. The simplest way
to account for this is to propose direct nucleophilic attack
by the sulfide at nitrogen, perhaps aided by prior forma-
tion of an adduct with acetonitrile.
In summary, a nearly ideal procedure for the sulfide
to sulfonyl sulfilimine transformation has been deveoped.
Almost quantitative yields are achieved from a diverse
set of sulfides and a broad range of the readily available
sulfonyl nitrenoid sources known as chloramine salts (R3-
SO2NClNa), essentially by simply stirring them together
in acetonitrile.
2,6-Dich lor o-9-th ia bicyclo[3.3.1]n on a n e-N-m eth ylsu l-
fon ylsu lfilim in e (7d ): yield after recrystallization from hot
1
2-butanone: 750 mg (99%) of white crystals, mp 223 °C; H
NMR (400 MHz, CDCl3): δ ) 2.01 (m, 1H), 2.22 (m, 4H), 2.47
(m, 1H), 2.78 (m, 2H), 2.96 (s, 3H), 3.35 (s, 2H), 4.47 (m, 1H),
5.12 (m, 1H); 13C NMR (125 MHz, CDCl3): δ ) 17.52, 22.39,
30.09, 30.37, 42.76, 49.55, 52.10, 52.70, 55.57; HRMS (FAB+)
calcd for C9H15Cl2NO2S2Na+ (M + Na+): 325.9819, found:
325.9812
2,6-Dih yd r oxy-9-th ia bycyclo[3.3.1]n on a n e-N-(4-m eth -
ylp h en yl)su lfon ylsu lfilim in e (7f): yield after recrystalli-
zation from H2O/iPrOH (9/1): 840 mg (98%) of white crystals,
mp 130 °C; 1H NMR (500 MHz, DMSO-d6): δ ) 1.70 (m, 1H),
1.81 (m, 3H), 2.16 (m, 4H), 2.28 (m, 1H), 2.36 (s, 3H), 2.87 (s,
1H), 2.99 (s, 1H), 3.97 (m, 1H), 4.43 (m, 1H), 7.31 (d, J ) 8.1
Hz, 2H), 7.63 (d, J ) 8.1 Hz, 2H); 13C NMR (125 MHz,
CDCl3): δ ) 16.08, 19.36, 28.42, 47.75, 51.07, 62.37, 68.65,
126.04, 129.60, 140.46, 142.33; HRMS (FAB+) calcd for C15H21
-
NO4S2 (M + H+): 344.0990, found: 344.0995.
2,6-Dia zid o-9-t h ia b ycyclo[3.3.1]n on a n e-N-(4-m et h yl-
p h en yl)su lfon ylsu lfilim in e (7 g): yield after recrystalliza-
tion from AcOH/H2O: 904 mg (92%) of white crystals, mp 162
°C; 1H NMR (400 MHz, CDCl3): δ ) 1.80 (m, 5H), 2.25 (m,
1H), 2.46 (s, 2H), 2.50 (m, 1H), 2.75 (m, 1H), 4.03 (m, 1H),
4.70 (m, 1H), 7.28 (d, J ) 8.4, 2H), 7.79 (d, J ) 3.4 Hz, 2H);
13C NMR (125 MHz, CDCl3): δ ) 16.18, 20.94, 21.00, 25.52,
25.75, 46,57, 48.82, 53.34, 59.05, 126.05, 129.50, 141.04,
142.27; HRMS (FAB+) calcd for C15H19N7O2S2 (M + H+):
394.1120, found: 394.1134.All other compounds (i.e., those in
Table 2) have been described before. Their identity has been
established by comparing their melting points and 1H NMR
spectra with the published data. Melting points are given in
Table 2.
Exp er im en ta l Section
Gen er a l P r oced u r e for th e P r ep a r a tion of Su lfil-
im in es fr om Su lfid es As Exem p lified for th e P r ep a r a tion
of 7e on a 120 m m ol Sca le. To a magnetically stirred solution
of 2,6-dichloro-9-thiabicyclo[3.3.1]nonane (6a ) (25 g, 0.12 mol)
in 475 mL of CH3CN (Fisher, A21-20, UN1648) was added
Chloramine-T trihydrate (40 g, 0.14 mol). The reaction was
stirred for 16h at rt and then quenched by addition of 800 mL
of CH2Cl2; Et2O or EtOAc can also be used. After NaCl and
the excess of the sodium salt 2 were removed by filtration,
the solvent was evaporated. The resulting solid product was
recrystallized from hot 2-butanone to give sulfilimine 7e (42.5
g, 97%) as a white solid, mp 183 °C.
2,6-Dich lor o-9-th ia bicyclo[3.3.1]n on a n e-N-p h en ylsu l-
fon ylsu lfilim in e (7a ): yield after recrystallization from
AcOH/H2O: 699 mg (86%), white crystals, mp 67 °C; 1H NMR
(400 MHz, CDCl3): δ ) 1.94 (m, 1H), 2.18 (m, 4H), 2.43 (m,
1H), 2.75 (m, 2H), 3.23 (s, 2H), 4.40 (m, 1H), 5.13 (m, 1H),
7.45 (m, 3H), 7.90 (m, 2H); 13C NMR (125 MHz, CDCl3): δ )
17.56, 22,39, 30.39, 49.09, 51.59, 52.62, 55.53, 126.06, 128.91,
Ack n ow led gm en t. We thank the National Institute
of General Medical Sciences, the National Institutes of
Health (GM-28384), the W. M. Keck Foundation, the
Skaggs Institute for Chemical Biology, and Novartis
Pharma AG for financial support.
1
Su p p or tin g In for m a tion Ava ila ble: Copies of H NMR
and 13C NMR spectra for compounds 7a -g. This material is
(17) J alsovszky, I.; Ruff, F.; Kajta´r-Peredy, M.; Ko¨vesdi, I.; Kucsman,
A. Tetrahedron 1986, 42, 5649-5656.
J O0012039