Reagent-controlled diastereoselective aminations with a new chiral nosyloxycarbamate

Article abstract of DOI:10.1016/S0040-4039(03)00558-6

The synthesis of a new chiral nosyloxycarbamate derived from Helmchen's auxiliary is described. Reactions performed with this aminating reagent successfully give the formation of diastereomeric allylic carbamates or diastereomeric aziridines starting from different kinds of olefins.

Full text of DOI:10.1016/S0040-4039(03)00558-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 3031–3034
Reagent-controlled diastereoselective aminations with a new
chiral nosyloxycarbamate
Stefania Fioravanti,* Alberto Morreale, Lucio Pellacani* and Paolo A. Tardella*
Dipartimento di Chimica dell’Universita` degli Studi di Roma ‘La Sapienza’, P. le Aldo Moro 2, I-00185 Roma, Italy
Received 14 February 2003; accepted 27 February 2003
Abstract—The synthesis of a new chiral nosyloxycarbamate derived from Helmchen’s auxiliary is described. Reactions performed
with this aminating reagent successfully give the formation of diastereomeric allylic carbamates or diastereomeric aziridines
starting from different kinds of olefins. © 2003 Elsevier Science Ltd. All rights reserved.
Arylsulfonyloxycarbamates (ArSO3NHCO2R) are use-
ful reagents for direct amination reactions. They are
stable compounds that can be decomposed in basic
media. Ethyl nosyloxycarbamate (NsONHCO2Et)1 and
other similar carbamates,2 were used either in direct
electrophilic or nucleophilic aziridinations3 of different
kind of olefins.
In particular the stoichiometric aziridination of olefins
has received relatively little attention.4 Atkinson and
co-workers achieved moderate to high diastereoselectiv-
ities with N-aminoquinazolinone derivatives.5 Attempts
to obtain chiral aziridination of styrene by (−)-bornyl
nosyloxycarbamate failed under the various conditions
employed.6 Poor diastereoselectivity was recently
observed in the addition reaction of chiral N-arylhy-
droxamates to prochiral olefins.7 In the past we
reported the synthesis of azidoformates derived from
chiral enol ethers that gave high diastereoselective
intramolecular cycloaddition8 and also the synthesis of
the optically active carbamoyl azide derived from
Oppolzer’s sultam affording amination reactions with
satisfactory diastereoselective induction.9
Asymmetric CꢀN bond formation is an important topic
in organic syntheses. Methods for reagent-controlled
stereoselective amination reactions are few in number.
We report here the preparation and the use of a new
chiral aminating agent, obtained from the chiral Helm-
chen’s alcohol 1 (Fig. 1). A simple synthetic sequence
provides the preparation of 2, without the need of
purification at any step (Scheme 1). The chiral carba-
mate 2 was obtained in 81% overall yield by reaction of
nosyl chloride with the hydroxycarbamate, prepared
Figure 1.
Scheme 1. Reagents and conditions: (i) triphosgene, pyridine, toluene, 0°C; (ii) NH2OH·HCl, K2CO3, Et2O, rt; (iii) NsCl, Et3N,
Et2O, 0°C.
* Corresponding author. Fax: +39-06-490631; e-mail: lucio.pellacani@uniroma1.it
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00558-6

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S. Fiora6anti et al. / Tetrahedron Letters 44 (2003) 3031–3034
from hydroxylamine and the chloroformate of the alco-
the starting material was collected in almost quantita-
tive amounts, the expected chiral nitrene (NCO2R*)
was trapped by 1-methylcyclohexene leading to the
formation of diastereomeric allylic12 carbamates 3
(Scheme 2) as the only products (45%) with a 30%
diastereomeric excess, as showed by NMR and HPLC
analyses performed on the crude reaction mixture.
hol 1.10
First of all, we tested the reactivity of 2 toward elec-
tron-rich species, such as ethyl 2-methylacetoacetate11
or 1-methylcyclohexene in the presence of calcium
oxide. While the former did not give any products, and
Scheme 2. Allylic amination of 1-methylcyclohexene.
Table 1. Aziridination of prochiral electron-poor olefins with 2 in CH2Cl2 at 0°C

S. Fiora6anti et al. / Tetrahedron Letters 44 (2003) 3031–3034
3033
Scheme 3. Aziridination of ethyl 2-acetylcrotonate.
Steric hindrance probably prevents the formation of the
aziridines, the main expected products,1 and since 3
cannot derive from the aziridines themselves, it follows
that the insertion reaction does indeed take place at this
allylic position.
4. For a recent review, see: Faul, M. M.; Evans, D. A. In
Asymmetric Oxidation Reactions; Katsuki, T., Ed.;
Oxford University Press: Oxford, 2001; pp. 115–128.
5. Atkinson, R. S. Tetrahedron 1999, 55, 1519–1559.
6. Banks, M. R.; Blake, A. J.; Cadogan, J. I. G.; Dawson, I.
M.; Gosney, I.; Grant, K. J.; Gaur, S.; Hodgson, P. K.
G.; Knight, K. S.; Smith, G. W.; Stevenson, D. E.
Tetrahedron 1992, 48, 7979–8006.
7. Aires-de-Sousa, J.; Prabhakar, S.; Lobo, A. M.; Rosa, A.
M.; Gomes, M. J. S.; Corvo, M. C.; Williams, D. J.;
White, A. J. P. Tetrahedron: Asymmetry 2001, 12, 3349–
3365.
On the contrary, we observed that 2 very efficiently
reacted with different prochiral electron-poor olefins,
giving the expected aziridines likely by the aza-Michael
pathway proposed by us.3 The results are listed in Table
1.
With a small excess of 2, the functionalized aziridines13
were obtained mostly in satisfactory yields and with
good diastereoselective induction, as shown by analyses
of 1H and 13C NMR spectra of the crude reaction
mixtures. Best results both for chemical yields and
diastereomeric inductions were obtained on b-oxo
enoates (entries 2–4).
8. de Santis, M.; Fioravanti, S.; Pellacani, L.; Tardella, P.
A. Eur. J. Org. Chem. 1999, 2709–2711.
9. Del Signore, G.; Fioravanti, S.; Pellacani, L.; Tardella, P.
A. Tetrahedron 2001, 57, 4623–4627.
10. General synthetic procedure. To a solution of triphosgene
(6.0 mmol; CAUTION: toxic if inhalated or swallowed)
in 40 mL of anhydrous toluene, commercially available
alcohol 1 (4.0 mmol) and freshly distilled pyridine (6.0
mmol) were added in 1 h at 0°C. The solution was stirred
for 24 h. After filtration, toluene was removed under
reduced pressure and the chloroformate was obtained as
a white solid in quantitative yield after crystallization
from pentane. This product (4.0 mmol) was stirred for 24
h in diethyl ether in the presence of hydroxylamine
hydrochloride (4.0 mmol), K2CO3 (4.0 mmol) and 80 ml
of H2O. After dilution with additional 100 mL of diethyl
ether, the solution was filtered and dried over Na2SO4.
Solvent removal gave the corresponding hydroxycarba-
mate (97% yield, white solid) that was reacted with
equimolar amounts of nosyl chloride and freshly distilled
triethylamine in anhydrous diethyl ether at 0°C. The
chiral nosyloxy carbamate 2 was obtained in 83% yield as
a pale yellow solid and stored at −20°C under argon. Mp:
118–119°C (from pentane); [h]D=+7.69 (c 3.9, CHCl3);
Another chiral nosyloxycarbamate 4 obtained in 78%
overall yield from (−)-8-phenylmenthol14 through the
procedure depicted above for 2, successfully aziridinates
ethyl 2-acetylcrotonate (Scheme 3).
At the best of our knowledge, these are the first exam-
ples reporting the successful use of chiral carbamates
giving asymmetric amination reactions. Owing to the
biological and synthetic importance of optical active
aziridines,15 examples of stereoselective reagent-con-
trolled amination here reported are interesting and very
promising for direct formation of chiral CꢀN bonds.
Acknowledgements
1
IR (CHCl3): 3496, 1771, 1537 cm−1; H NMR (300 MHz,
This research was carried out within the framework of
the National Project ‘Stereoselezione in Sintesi Organ-
ica. Metodologie ed Applicazioni’, supported by the
Italian Ministero dell’Istruzione dell’Universita` e della
Ricerca (MIUR) and by the Universita` degli Studi di
Roma ‘La Sapienza’.
CDCl3): l 0.62 (s, 3H), 0.79 (s, 3H), 0.85 (s, 3H),
1.13–1.38 (m, 2H), 1.40–1.55 (m, 1H), 1.55–1.72 (m, 1H),
1.80 (d, J=4.5 Hz, 1H), 1.96 (s, 3H), 2.29 (s, 3H), 3.76
(d, J=6.9 Hz, 1H), 4.88 (d, J=6.9 Hz, 1H), 5.63 (s, 1H),
6.80 (s, 1H), 7.02 (s, 1H), 7.23–7.34 (m, 4H), 7.41–7.58
(m, 1H), 8.19–8.34 (m, 4H), 8.89 (s, 1H); 13C NMR (75
MHz, CDCl3): l 10.8, 20.6, 21.1, 21.3, 27.4, 31.8, 47.3,
48.3, 50.2, 67.1, 84.5, 123.9, 128.1, 128.4, 129.4, 131.2,
131.6, 132.6, 136.5, 138.1, 139.0, 150.9, 155.1. ESI MS
m/z 658 (M++1).
References
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3. Fioravanti, S.; Pellacani, L.; Stabile, S.; Tardella, P. A.;
Ballini, R. Tetrahedron 1998, 54, 6169–6176.
11. This compound easily reacted with NsONHCO2Et. See:
Fioravanti, S.; Morreale, A.; Pellacani, L.; Tardella, P. A.
Tetrahedron Lett. 2001, 42, 1171–1173.
12. For a recent review of allylic amination, see: Johannsen,
M.; Jørgensen, K. A. Chem. Rev. 1998, 98, 1689–1708.

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S. Fiora6anti et al. / Tetrahedron Letters 44 (2003) 3031–3034
13. General aziridination procedure. To a stirred solution of
the substrate (2.0 mmol) in CH2Cl2, CaO and 2 were
added batchwise at 0°C in the ratio reported in Table 1.
Upon completion (3–6 h) the crude mixture was diluted
with 10 mL of CH2Cl2 and filtered. After solvent evapo-
ration under reduced pressure, the residue was purified by
flash chromatography on silica gel (70:30, hexane/ethyl
acetate). The aziridines reported in entry 1 were obtained
as pure distereomers by HPLC separation (80:20, hexane/
1H), 3.42 (s, 1H), 3.84 (d, J=6.9 Hz, 1H), 5.05 (d, J=6.9
Hz, 1H), 5.54 (s, 1H), 6.82 (s, 1H), 7.10 (s, 1H), 7.20–7.51
(m, 5H); 13C NMR (75 MHz, CDCl3): l 11.5, 17.7, 20.8,
21.5, 23.5, 28.0, 30.5, 32.2, 38.3, 47.3, 47.9, 48.3, 50.1,
51.8, 67.4, 85.1, 127.8, 128.0, 129.1, 132.1, 137.1, 137.8,
157.8, 199.4, 200.9; ESI MS m/z 594 (M++1).
14. Recently we reported that both (−)-8-phenylmenthol and
Helmchen’s alcohol are valuable chiral auxiliaries. See:
Fioravanti, S.; Morreale, A.; Pellacani, L.; Tardella, P. A.
J. Org. Chem. 2002, 67, 4972–4974.
1
ethyl acetate). Major diastereomer: H NMR (300 MHz,
15. For recent reviews, see: (a) Dodd, R. H. Molecules 2000,
5, 293–298; (b) McCoull, W.; Davis, F. A. Synthesis 2000,
1347–1365.
CDCl3): l 0.54 (s, 3H), 0.65 (s, 3H), 0.95 (s, 3H),
1.05–1.71 (m, 7H), 1.74 (d, J=3.9 Hz, 1H), 1.81–2.46 (m,
2H), 1.98 (s, 3H), 2.39 (s, 3H), 2.51 (s, 3H), 2.72–2.90 (m,