M. Ardej-Jakubisiak et al. / Tetrahedron: Asymmetry 18 (2007) 2507–2509
Table 3. Synthesis of optically active N-sulfinylimines
2509
20
20
Entry
Sulfinimine
Method
Yield (%)
Observed ½aꢁD
Lit. ½aꢁD
1
2
3
(S)-3aa
(S)-3ac
(R)-3ba
t-BuOK
t-BuOK
t-BuOK
90
88
58
+111.7 (1.1, CHCl3)
+38.1 (1.0, CHCl3)
ꢀ104.7 (1.0, CHCl3)
+114 (1.0, CHCl3)8
+37.9 (1.49, CHCl3)4b
ꢀ101 (1.0, CHCl3)14
O-
K+
Ar
O
S
Ar-CHO
t
-BuOK
O
S
O
S
t
-BuOH
+
R
NH2
N- K+
H
R
N
H
R
O
S
OH
Ar
O
S
-H2O
t
-BuOH
+
t
-BuOK
R
N
Ar
R
N
H
Scheme 4. Possible mechanism of the formation of sulfinimines.
using (S)-(ꢀ)-BINOL as the chiral solvating agent13 and a
sample of 3ba by chiral HPLC. Racemization was negligi-
ble in all cases.
4. (a) Annunziata, R.; Cinquini, M.; Cozzi, F. J. Chem. Soc.,
Perkin Trans. 1 1982, 339; (b) Davis, F. A.; Reddy, R. E.;
Szewczyk, J. M.; Portonowo, P. S. Tetrahedron Lett. 1993,
34, 6229–6232.
5. Davis, F. A.; Reddy, R. E.; Reddy, R. T. J. Org. Chem. 1992,
57, 6387–6389.
A possible mechanism for the formation of the sulfinimines
is shown in Scheme 4. The first steps include formation of
the aza-anion of sulfinamide and its addition to the alde-
hyde. Elimination of water gives N-sulfinimines. Usually
5–10 min after addition of the aldehyde, a precipitate is
formed, which dissolves gradually within a few hours.
6. Davis, F. A.; Reddy, R. E.; Szewczyk, J. M.; Reddy, G. V.;
Portonovo, P. S.; Zhang, H.; Fanelli, D.; Reddy, R. T.; Zhou,
P.; Carroll, P. J. Org. Chem. 1997, 62, 2555–2563.
7. (a) Liu, G. C.; Cogan, D. A.; Owens, T. D.; Tang, T. P.;
Ellman, J. A. J. Org. Chem. 1999, 64, 1278–1284; (b) Davis,
F. A.; Zhang, Y.; Andemichael, Y.; Fang, T.; Fanelli, D. L.;
Zhang, H. J. Org. Chem. 1999, 64, 1403–1406.
8. Higashibayashi, S.; Tohmiya, H.; Mori, T.; Hashimoto, K.;
Nakata, M. Synlett 2004, 457–460.
3. Conclusion
9. Jiang, Z.-Y.; Chan, W. H.; Lee, A. W. M. J. Org. Chem. 2005,
70, 1081–1083.
10. Huang, Z.; Zhang, M.; Wang, M.; Qin, Y. Synlett 2005,
1334–1336.
In conclusion we have developed a simple and efficient pro-
cedure for the synthesis of N-sulfinyl aldimines from sulfin-
amides and aldehydes. The reaction can be carried out
without any special protection from air or moisture. The
yields for aromatic sulfinimines are very good. As a result
of the strongly basic conditions the yields of the aliphatic
sulfinimines are lower. The procedure is applicable for
the synthesis of optically active sulfinimines. It may also
be useful for the preparation of large libraries of aromatic
amines.
11. General experimental procedure for the synthesis of sulfini-
mines: The reaction was carried out in a round bottom flask
not protected from either air or moisture. To a solution of
sulfinamide (0.71 mmol) in methanol (3.5 mL) was added
potassium t-butoxide or sodium hydroxide (0.71 mmol). The
mixture was stirred for 15 min and aldehyde (1.065 mmol)
then added. The reaction mixture was stirred at rt for 16 h.
Methanol was evaporated and the residue dissolved in
methylene chloride (2 mL) and aqueous NH4Cl solution
(2 mL). The organic layer was separated and the water phase
extracted twice with CH2Cl2 (2 mL). The organic extracts
were dried over MgSO4. After evaporation of the solvent, the
crude product was purified by chromatography on silica gel
using a mixture of ethyl acetate–hexane as an eluent. All
compounds have spectral data identical to those published in
the literature.
References
1. (a) Zhou, P.; Chen, B. C.; Davis, F. A. Tetrahedron 2004, 60,
8003–8030; (b) Davis, F. A.; Yang, B.; Deng, J. H.; Wu, Y.
Z.; Zhang, Y.; Rao, A.; Fang, T. N.; Goswami, R.; Prasad,
K. R.; Nolt, M. B.; Anilkumar, G. Phosphorus Sulfur 2005,
180, 1109–1117.
20
12. Observed specific rotation: ½aꢁD ¼ þ80:5 (c 1.1, CHCl3), lit.7b
20
½aꢁD ¼ þ80:2 (c 1.2, CHCl3).
2. Ellman, J. A.; Owens, T. D.; Tang, P. T. Acc. Chem. Res.
2002, 35, 984–995.
13. Kawe˛cki, R., Ardej-Jakubisiak, M., in press.
14. Ruano, J. L. G.; Fernandez, I.; Catalina, M. del P.; Cruz, A.
A. Tetrahedron: Asymmetry 1996, 7, 3407–3414.
3. Morton, D.; Stockman, R. A. Tetrahedron 2006, 62, 8869–
8905.