Imination of sulfoxides using 3-acetoxyaminoquinazolinone as nitrogen source in the presence of hexamethyldisilazane

Article abstract of DOI:10.1016/j.tetlet.2005.05.109

The reaction of 3-acetoxyaminoquinazolinone (QNHOAc) with various sulfoxides in the presence of HMDS as an acetic acid scavenger, afforded the corresponding sulfoximides in good yields. Sulfoximidation of phenyl methyl sulfoxide using a Q*NHOAc having a s

Full text of DOI:10.1016/j.tetlet.2005.05.109

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 5225–5227
Imination of sulfoxides using 3-acetoxyaminoquinazolinone
as nitrogen source in the presence of hexamethyldisilazane
Semistan Karabuga,a Cavit Kazaz,b Hamdullah Kilic,b Sabri Ulukanlia,* and Ayhan Celikc
aDepartment of Chemistry, Faculty of Science and Letters, The University of Kafkas, 36100 Kars, Turkey
bDepartment of Chemistry, Faculty of Science and Letters, Ataturk University, 25240 Erzurum, Turkey
cEdinburgh Centre for Protein Technology, Chemistry Department, University of Edinburgh,
KingÕs Buildings, West Mains Road, Edinburgh EH9 3JJ, UK
Received 30 March 2005; revised 12 May 2005; accepted 25 May 2005
Available online 13 June 2005
Dedicated to Dr. R. S. Atkinson on the occasion of his 65th birthday
Abstract—The reaction of 3-acetoxyaminoquinazolinone (QNHOAc) with various sulfoxides in the presence of HMDS as an acetic
acid scavenger, afforded the corresponding sulfoximides in good yields. Sulfoximidation of phenyl methyl sulfoxide using a
Q*NHOAc having a stereogenic centre on its 2-position gave the products in 1.3:1 ratio of diastereomers.
ꢀ 2005 Elsevier Ltd. All rights reserved.
The discovery of sulfoximides dates back to the late
1940s and early 1950s.1 Since then, significant attention
has been given to sulfoximides by synthetic organic
chemists. Due to stereogenicity at the sulfur atom, sulf-
oximides have been used in pseudopeptides,2,3 amino
acids and amino alcohols4 as well as in C–C bond for-
mation.5–8 Recently, Bolm,9,10 Reggelin1 and Tye11
and their respective co-workers independently intro-
duced sulfoximides as chiral ligands in asymmetric syn-
thesis. A number of methods are known for the
transformation of sulfoxides into sulfoximides using
tert-butyloxycarbonyl azide (BocN3),12,13 O-mesitylene-
sulfonylhydroxylamine (MSH),14,15 chloramine T16,17
for the preparation of aziridines.24 Where R is stereo-
genic centre, high,25,26 or even completely27 diastereo-
selective aziridinations (reagent-controlled) are obtained
with moderate to good yields. We have recently reported
that the substrate-controlled aziridinations of 8-phenyl-
menthol-derived a,b-unsaturated esters give aziridines
completely diastereoselectively and the yields of these
aziridines are greatly improved by the presence of hexa-
methyldisilazane (HMDS)28,29 (Scheme 1). Additionally,
a chiral 3-aminoquinazolinone 1 when converted into its
3-N,N-diacylaminoquinazolinone derivative 4, is also an
enantioselective acylating agent for racemic amines, for
example 4a, by means of kinetic resolution in up to 95%
ee30–32 (Scheme 1).
or
[N-(p-tolylsulfinyl)imino]phenyliodinane
(PhI =
NTs)18–21 or by an electrochemical process using N-
aminophthalimide.22,23 However, there is still a require-
ment for a general procedure for the conversion of sulf-
oxides into sulfoximides.
Although imination of dimethylsulfoxide (DMSO) by
LTA oxidation of N-aminoheterocycles has been
reported,33 surprisingly, to the best of our knowledge,
there are no reports on a general procedure for imina-
tion of sulfoxides using 3-amino-2-ethylquinazolinone
1 (R = ethyl) under the same conditions. Therefore, we
report, herein, the first imination of sulfoxides using
3-acetoxyamino-2-ethylquinazolinone 2 (QNHOAc).
Aziridination of alkenes by lead tetraacetate (LTA) oxi-
dations of 3-aminoquinazolinones 1 is a known method
Keywords: Sulfoximidation; 3-Acetoxyaminoquinazolinone; Sulfox-
ides; Sulfoximides; Sulfoximines; Lead tetraacetate; HMDS;
Diastereoselectivity.
Initially, we examined the imination of DMSO with
QNHOAc 2 and followed the general aziridination
procedure (À18 ꢁC to rt) using an equimolar quantity of
DMSO. This reaction resulted in the desired sulfoximide
*
Corresponding author. Tel.: +90 4742120201/128; fax: +90
4742122706; e-mail: ulukanli@kafkas.edu.tr
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.05.109

5226
S. Karabuga et al. / Tetrahedron Letters 46 (2005) 5225–5227
Q
N
Ph
CH2Cl2
-20 oC to rt
Ph
LTA / CH2Cl2
-20 oC to -25 o
Q
N
d.r: >50:1
R=CHOHBut
C
NHOAc
O
R
N
R*O2C
Q
N
NH2
2
CH2Cl2
-20 oC to rt
1
R*O2C
1. PHCOCl, Pyr, CH2Cl2
2. PriCOCl, Pyr, CH2Cl2
d.r: >50:1
R=Et
R*=8-phenymenthol
Q
Q
N
H
N
H
Me
O
N
O
N
O
Me
H
+
4a
Pri
Pri
Ph
Ph
O
4 R=CHPriOTBDMS
(85%) 95% ee
Scheme 1.
O
S
O
S
O
NQ
Ph
R
O
N
Q
NQ
7
+
S
CH2Cl2, HMDS
-78 oC to -10 oC
H
QNHOAc
S
N
O
CH2Cl2, HMDS
-78 oC to -10 o
Ph
R
5
6
NHOAc
C
2
8
2 QNHOAc
Scheme 2.
Scheme 3.
Table 1. Imination of phenylalkylsulfoxides (2 equiv) using QNHOAc
2 at À78 to À10 ꢁC in the presence of HMDS
5 as a crystalline product (mp 130–132 ꢁC) in 35% yield
in addition to QH 6, which is the general by-product of
QNHOAc 2 aziridinations of alkenes, especially where
electron deficiency is present28,29 (Scheme 2). On
increasing the molar equivalents of DMSO from 1 to 2
under the same conditions, the yield increased to 60%.
Due to the instability of QNHOAc 2 (stable at <0 ꢁC),
we lowered the imination temperature to À78 ꢁC and
finished at À10 ꢁC by adding a saturated NaHCO3 solu-
tion, and extracting with CH2Cl2, to give an 80% yield.
Experience from the aziridination process led us to use
HMDS (2 equiv relative to QNH2 1) to scavenge AcOH
and this gave almost exclusively the sulfoximide 5 (95%)
(Scheme 2).
Entry Sulfoxides
R
Products Mp (ꢁC) Yielda (%)
1
2
3
4
5
6
7a
7b
7c
7d
7e
7f
Me
Et
8a
8b
8c
8d
145–147 57
155–157 61
119–121 61
127–128 60
136–138 62
161–163 70
iPr
tBu
c-Hexyl 8e
Bn 8f
methylene protons of the ethyl of the quinazolinone ring
in 8f resonated at 3.11 ppm as a multiplet, surprisingly,
the other benzylic methylene protons appeared as a sin-
glet at 4.71 ppm. All the sulfoximides 8a–f were white
crystalline materials (from ethanol) and had spectro-
scopic data as well as elemental analyses ( 0.2) consis-
tent with the sulfoximide structures (Table 1).
We then turned our attention to the imination of phen-
ylalkylsulfoxides 7a–f using QNHOAc 2 under the opti-
mised condition as described above. The sulfoximides
8a–f34 were obtained in good yields (Scheme 3). The
1H NMR spectrum of the product from the imination
of phenyl methyl sulfoxide with QNHOAc 2 showed
that the methylene protons of the ethyl group in the
products 8a–f were diastereotopic as evidenced by a
multiplet at 3.17 ppm. For example, the methylene pro-
tons of the ring ethyl in 8b appeared at 3.17 and
3.51 ppm as two multiplets, respectively. Similarly, the
The advantage of using 3-aminoquinazolinones in sulf-
oximidation, in particular, is the possibility of having
a stereogenic centre at C-2, for example in Q*NHOAc
9, which can give products diastereoselectively. A diaste-
reoselective version of our procedure was carried out
using lactic acid-derived Q*NHOAc 9, and phenyl
methyl sulfoxide giving sulfoximide 10 in 49% yield,

S. Karabuga et al. / Tetrahedron Letters 46 (2005) 5225–5227
5227
16. Heintzelmann, R. W.; Swern, D. Synthesis 1976, 731–733.
17. Huang, S.; Swern, D. Phosphorus Sulfur 1976, 1, 309–314.
18. Tye, H. Tetrahedron Lett. 2002, 43, 9421–9423.
19. Leca, D.; Song, K.; Amatore, M.; Fensterbank, L.;
Lacote, E.; Malacria, M. Chem. Eur. J. 2004, 10, 906–916.
20. Lacote, E.; Amatore, M.; Fensterbank, L.; Malacria, M.
Synlett 2002, 116–118.
O
S
Ph
N
O
NQ*
7a
N
O
S
CH2Cl2, HMDS
Ph
10 dr: 1.3:1
OH NHOAc
-78 oC to -10 o
49%
C
21. Cren, S.; Kinahan, T. C.; Skinner, C. L.; Tye, H.
Tetrahedron Lett. 2002, 43, 2749–2751.
9 Q*NHOAc
22. Siu, T.; Yudin, A. K. Org. Lett. 2002, 4, 1839–1842.
23. Siu, T.; Picard, C. J.; Yudin, A. K. J. Org. Chem. 2005, 70,
932–937.
Scheme 4.
24. Atkinson, R. S. Tetrahedron 1999, 55, 1519–1559.
25. Atkinson, R. S.; Fawcett, J.; Claxton, T. A.; Lochrie, I. S.
T.; Ulukanli, S. J. Chem. Soc., Perkin Trans. 2 2002, 819–
828.
but, with virtually no diastereoselectivity (dr: 1.3:1)
(Scheme 4).
26. Atkinson, R. S.; Claxton, T. A.; Lochrie, I. S. T.;
Ulukanli, S. Tetrahedron Lett. 1998, 39, 5113–5116.
27. Atkinson, R. S.; Ayscough, A. P.; Gattrell, W. T.;
Raynham, T. M. J. Chem. Soc., Perkin Trans. 1 1998,
2783–2793.
In conclusion, we have developed a new method for the
conversion of sulfoxides into sulfoximides using
QNHOAc 2. The yields were good in the presence of
HMDS.
28. Atkinson, R. S.; Barker, E.; Ulukanli, S. J. Chem. Soc.,
Perkin Trans. 1 1998, 583–589.
Acknowledgements
29. Ulukanli, S.; Karabuga, S.; Celik, A.; Kazaz, C. Tetrahed-
ron Lett. 2005, 46, 197–199.
30. Al-Sehemi, A. G.; Atkinson, R. S.; Fawcett, J. J. Chem.
Soc., Perkin Trans. 1 2002, 257–274.
31. Al-Sehemi, A. G.; Atkinson, R. S.; Fawcett, J.; Russell, D.
R. J. Chem. Soc., Perkin Trans. 1 2000, 4413–4421.
32. Al-Sehemi, A. G.; Atkinson, R. S.; Fawcett, J.; Russell, D.
R. Tetrahedron Lett. 2000, 41, 2239–2242.
33. Atkinson, R. S. In Nitrenes and Azides, Reactivity and
Utility; Scriven, E. F. V., Ed.; Academic Press: NewYork,
1984, pp 247–295.
We would like to thank Dr. Ali Gunes for his proofread-
ing of this manuscript. We also thank the Turkish Scien-
tific Research Council (Grant TBAG 2322 (103T071))
for its generous support of this work. We are also grate-
ful to the Department of Chemistry at Ataturk Univer-
sity for the use of the 400 MHz NMR facility and Dr.
Ebru Mete for elemental analyses.
References and notes
34. Typical experimental procedure: 3-Amino-2-ethyl-quinazo-
linone QNH2 1 (0.3 g, 1.58 mmol) and acetic acid-free
lead tetraacetate (LTA) (0.77 g, 1.75 mmol) were added
alternately and continuously in very small portions over
15 min to a vigorously stirred solution of dry dichloro-
methane (6 cm3) at À40 ꢁC. The mixture was then stirred
for a further 5 min to give a solution of the 3-acetoxy-
aminoquinazolinone. The temperature was lowered to
À78 ꢁC, before dropwise addition of the phenyl methyl
sulfoxide (0.44 g, 3.17 mmol) as a solution in dichloro-
methane (3 cm3) containing HMDS (0.51 g, 3.17 mmol)
and then allowing the temperature of the solution to rise
to À10 ꢁC (ꢀ1.5–2 h) with continuous stirring. Saturated
aqueous sodium hydrogen carbonate (30 cm3) was added
and the mixture extracted with dichloromethane
(3 · 30 cm3). The combined organics were washed with
water (3 · 30 cm3), dried with sodium sulfate and the
solvent removed by evaporation under reduced pressure.
The crude product crystallised on addition of ethanol to
give sulfoximide 8a as a colourless solid (0.3 g, 57%), mp
145–147 ꢁC (from ethanol) IR (in CH2Cl2 solution) mmax
cmÀ1: 3479w, 3011w, 2929w, 1675s, 1608w, 1591s and
1568w. 1H NMR (CDCl3, 400 MHz): d 1.35 (3H, t,
J 7.3 Hz, CH2CH3), 3.17 (2H, m, CH2CH3), 3.31 (3H, s,
PhSCH3), 7.39–7.75 (m, 6-H, 7-H, 8-H (Q) and 3H (Ph)),
8.21 (1H, dd, J 8.2 and 1.1 Hz, 5-H (Q)) and 8.33 (2H, dd,
8.4 and 1.7 Hz, 2H (Ph)). 13C NMR (CDCl3, 100 MHz): d
10.8, 28.2, 43.8, 121.3, 126.2, 127.3, 128.8, 129.6, 134.1,
137.3, 146.8, 161.5 and 161.8). Elemental analysis calcu-
lated for C17H17N3O2S: C, 62.36; H, 5.23; N, 12.83; S,
9.79. Found: C, 62.13; H, 5.35; N, 12.97; S, 9.87.
1. Reggelin, M.; Weinberger, H.; Spohr, V. Adv. Synth.
Catal. 2004, 346, 1295–1306, and references cited therein.
2. Bolm, C.; Moll, G.; Kahmann, J. D. Chem. Eur. J. 2001, 7,
1118–1128.
3. Bolm, C.; Kahmann, J. D.; Moll, G. Tetrahedron Lett.
1997, 38, 1169–1172.
4. Gais, H.-J.; Loo, R.; Das, P.; Raabe, G. Tetrahedron Lett.
2000, 41, 2851–2854.
5. Pyne, S. G.; OÕMeara, G.; David, D. M. Tetrahedron Lett.
1997, 38, 3623–3626.
6. Pyne, S. G.; Dong, Z.; Skelton, B. W.; White, A. H. J.
Org. Chem. 1997, 69, 2337–2343.
7. Craig, D.; Geach, N. J.; Pearson, C. J.; Slawin, A. M. Z.;
White, A. J. P.; Williams, D. J. Tetrahedron 1995, 51,
6071–6098.
8. Bosshammer, S.; Gais, H.-J. Synlett 1998, 99–101.
9. Bolm, C.; Simic, O.; Martin, M. Synlett 2001, 1878–
1880.
10. Bolm, C.; Verrucci, M.; Simic, O.; Cozzi, P. G.; Raabe,
G.; Okamura, H. Chem. Commun. 2003, 2826–2827.
11. Kinahan, T. C.; Tye, H. Tetrahedron: Asymmetry 2001,
12, 1255–1257.
12. Bach, T.; Korber, C. Tetrahedron Lett. 1998, 39, 5015–
5016.
13. Bach, T.; Korber, C. Eur. J. Org. Chem. 1999, 1033–1039.
14. Tamura, Y.; Matsushima, H.; Minamikawa, J.; Sumoto,
M. I. Tetrahedron 1975, 31, 3035–3040.
15. Allenmark, S.; Claeson, S.; Lowendahl, C. Tetrahedron:
Asymmetry 1996, 7, 361–364.