3
188
G. Bégis et al.
SHORT PAPER
13C NMR13
IR (film): 3335, 2978, 2924, 2851, 1705, 1514, 1365, 1171 cm–1.
(100 MHz, DMSO): d = 14.0, 14.8, 59.4, 61.6, 61.9,
8
0.3, 101.6, 126.0, 127.2, 127.3, 127.5, 127.6, 134.7, 136.9, 156.5.
1
H NMR (500 MHz, 330 K, CDCl ): d = 0.47–0.53 (m, 2 H), 0.59–
3
+
HRMS: m/z [MNa ] calcd for C H NNaO : 364.15247; found:
0.68 (m, 2 H), 0.95–1.19 (m, 5 H), 1.40 [s, 9 H, C(CH ) ], 1.54–1.71
2
0
23
4
3 3
3
64.15313.
(m, 4 H), 1.84–1.89 (m, 1 H), 2.23–2.28 (m, 1 H, CHN), 4.54 (br s,
1
H, NH).
Anal. Calcd for C H NO : C, 70.36; H, 6.79; N, 4.10. Found: C,
20
23
4
1
3
7
0.32; H, 6.80; N, 4.10.
C NMR (125 MHz, 330 K, CDCl ): d = 12.3, 26.1, 26.2, 26.5,
7.2, 28.4, 32.1, 32.7, 40.7, 79.1, 156.4.
3
2
Compound 8
Mp: 93–95 °C (hexane); [a]D +6.0 (c = 0.55, CH Cl ).
+
HRMS: m/z [MH ] calcd for C H NO : 240.19634; found:
2
0
14 26
2
2
2
2
40.19634.
Anal. Calcd for C H NO : C, 70.25; H, 10.53; N, 5.83. Found: C,
70.08; H, 10.61; N, 5.82.
Compound 9
Mp: 92.5–94.5 °C (hexane); [a]D –4.5 (c = 1.12, CH Cl ).
14 25
2
2
6
2
2
Aminocyclopropanation; General Procedure
A solution of 3-diethoxymethyl-4,5-diphenyl-2-oxazolidinone 7, 8
or 9 (0.427 g, 1.25 mmol) in anhyd CH Cl (1.5 mL) was added via
Acknowledgment
2
2
We would like to thank Professor Barry Lygo for providing us with
experimental procedures and a sample of phase-transfer catalyst
used in the preparation of alkene 21 and AstraZeneca for provi-
syringe pump over 6 h to a vigorously stirred mixture of zinc amal-
gam (0.82 g, 12.5 mmol), zinc chloride (1 M solution in Et O, 1.25
10
2
mL, 1.25 mmol), chlorotrimethylsilane (0.79 mL, 6.25 mmol) and
alkene (1.0 mmol) in anhyd Et O (5.5 mL) under N at reflux. The
ding a studentship (to GB).
2
2
mixture was stirred for 16 h and then allowed to cool to r.t. The re-
action mixture was quenched with sat. aq NaHCO solution (10 mL) References
3
and after stirring for 20 min, the mixture was filtered and the sepa-
(
1) For examples see: (a) Salaün, J. Top. Curr. Chem. 2000,
rated zinc was washed with CH Cl (10 mL). The organic solvents
2
2
207, 1. (b) Salaün, J.; Baird, M. S. Curr. Med. Chem. 1995,
were removed in vacuo and the aqueous layer was extracted with
2, 511.
CH Cl (3 × 10 mL). The combined organic extracts were washed
2
2
(
2) (a) Aggarwal, V. K.; de Vicente, J.; Bonnert, R. V. Org. Lett.
001, 3, 2785. (b) de Meijere, A.; Kozhushkov, S. I.;
Savchenko, A. I. J. Organomet. Chem. 2004, 689, 2033.
c) Ye, A.; Komarov, I. V.; Kirby, A. J.; Jones, M. J. Jr. J.
with brine (10 mL), dried (MgSO ), filtered and concentrated in
4
2
vacuo. The crude product was then purified by flash column chro-
matography.
(
Org. Chem. 2002, 67, 9288. (d) Lavallo, V.; Mafhouz, J.;
Canac, Y.; Donnadieu, B.; Schoeller, W. W.; Bertrand, G. J.
Am. Chem. Soc. 2004, 126, 8670. (e) Ogawa, A.; Takami,
N.; Nanke, T.; Ohya, S.; Hirao, T. Tetrahedron 1997, 53,
Removal of the Chiral Auxiliary; General Procedure
A mixture of cyclopropane (0.34 mmol), di-tert-butyl dicarbonate
(
146 mg, 0.67 mmol), Pd(OH) /C (20%, 52 % water, 71 mg, 0.05
2
mmol) and THF (8.5 mL) was hydrogenated at 5.5 bar at 30 °C for
h. The reaction mixture was filtered, concentrated in vacuo and
12895.
7
(
(
(
3) Bégis, G.; Cladingboel, D.; Motherwell, W. B. Chem.
Commun. 2003, 2656.
4) Es-Sayed, M.; Gratkowski, C.; Krass, N.; Meyers, A. I.; de
Meijere, A. Synlett 1992, 962.
5) Akiba, T.; Tamura, O.; Terashima, S. In Org. Synth. Coll.
Vol. X; Wiley: New York, 2004, 374.
6) Gmeimer, P.; Bollinger, B. Synthesis 1995, 168.
7) CCDC Nos. 282755 and 282756 contain the crystallographic
data for 14 and 16. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
(8) (a) Magar, S. S.; Desai, S. C.; Fuchs, P. L. J. Org. Chem.
1992, 57, 5360. (b) Rahman, N. A.; Fleming, I. Synth.
Commun. 1993, 23, 1583.
purified by flash column chromatography to give the desired Boc-
protected aminocyclopropane.
(
4S,5R)-3-[(1R,2S)-2-Cyclohexylcyclopropyl]-4,5-diphenyl-
oxazolidin-2-one (10)
Mp 136–138.5 °C (EtOAc–hexane); [a]
CHCl ).
1
8
–106.9 (c = 1.07,
D
(
(
3
IR (film): 2924, 2851, 1751, 1456, 1406, 1265, 1196, 1078, 1026,
–1
7
41, 698 cm .
1
H NMR (500 MHz, CDCl ): d = 0.28–0.37 (m, 1 H, CH CHCH ),
3
2
2
0
2
2
.67–0.73 (m, 1 H), 0.73–0.81 (m, 2 H, cyclopropyl), 0.88–0.97 (m,
H), 0.99–1.15 (m, 4 H), 1.39–1.52 (m, 2 H), 1.55–1.66 (m, 2 H),
.17 (dt, J = 3.5, 6.7 Hz, 1 H, CHNR ), 4.82 (d, J = 8.0 Hz, 1 H,
2
PhCHN), 5.73 (d, J = 8.0 Hz, 1 H, PhCHO), 6.86–6.90 (m, 2 H, Ph),
(9) (a) Asai, A.; Hasegawa, A.; Ochiai, K.; Yamashita, Y.;
Mizukami, T. J. Antibiotics 2000, 53, 81. (b) Armstrong,
A.; Scutt, J. N. Chem. Commun. 2004, 510.
10) Lygo, B.; Andrews, B. I. Acc. Chem. Res. 2004, 37, 518; and
references therein.
11) The enantiomeric excess of alkene 21 was > 97% by chiral
6
.95–6.99 (m, 2 H, Ph), 7.01–7.11 (m, 6 H, Ph).
1
3
C NMR (125 MHz, CDCl ): d = 13.6, 25.7, 25.8, 26.2, 30.2, 32.1,
3
(
(
4
1
0.4, 66.8, 79.6, 125.9, 127.6, 127.76, 127.78, 128.1, 128.2, 134.3,
34.5, 158.2.
+
HRMS: m/z [M ] calcd for C H NO : 361.20933; found:
HPLC after a single recrystallisation.
2
4
27
2
1
3
61.20933.
(12) Yield calculated by H NMR, the cyclopropane product was
contaminated with oxazolidinone 5. The stereochemistry
was assigned analogously on the basis of H NMR coupling
constants.
Anal. Calcd for C H NO : C, 79.74; H, 7.53; N, 3.87. Found: C,
24
27
2
1
7
9.64; H, 7.56; N, 3.87.
(
13) Traces of acid and water in CDCl can cause partial
tert-Butyl [(1R,2S)-2-Cyclohexylcyclopropyl]carbamate (17)
3
2
0
degradation to the N-formyl derivative.
Mp 65–67 °C (petroleum ether–Et O); [a]
–47.7 (c = 1.32,
2
D
CHCl ).
3
Synthesis 2005, No. 19, 3186–3188 © Thieme Stuttgart · New York