RSS-Feed abonnieren
DOI: 10.1055/s-2005-864824
The Highly Diastereoselective Synthesis of Oxazolidines Derived from Ketones and Pseudoephedrine or Ephedrine
Publikationsverlauf
Publikationsdatum:
23. März 2005 (online)
![](https://www.thieme-connect.de/media/synlett/200506/lookinside/thumbnails/10.1055-s-2005-864824-1.jpg)
Abstract
2,2-Dialkyl-3,4-dimethyl-5-phenyloxazolidines and 2-alkyl-2-aryl-3,4-dimethyl-5-phenyloxazolidines are formed with high diastereoselectivity from ketones and pseudoephedrine or ephedrine in the presence of scandium triflate and 4 Å molecular sieves.
Key words
amino alcohols - heterocycles - ketones - scandium - stereoselective
-
1a
Abdallah H.Grée R.Carrié R. Tetrahedron Lett. 1982, 23: 503 -
1b
Ito Y.Amino Y.Nakatsuka M.Saegusa T. J. Am. Chem. Soc. 1983, 105: 1586 -
1c
Alexakis A.Sedrani R.Mangeney P.Normant JF. Tetrahedron Lett. 1988, 29: 4411 -
1d
Real SD.Kronenthal DR.Wu HY. Tetrahedron Lett. 1993, 34: 8063 -
1e
Frey LF.Tillyer RD.Caille A.-S.Tschaen DM.Dolling U.-H.Grabowski EJJ.Reider PJ. J. Org. Chem. 1998, 63: 3120 -
1f
Farfán N.Höpfl H.Santillan R.Ochoa ME.Gutiérrez A. Tetrahedron: Asymmetry 1999, 10: 799 -
1g
Rigby JH.Cavezza A.Heeg MJ. Tetrahedron Lett. 1999, 40: 2473 -
1h
Agami C.Couty F. Eur. J. Org. Chem. 2004, 677 - 2
Katritzky AR.Feng D.Qi M. Tetrahedron Lett. 1998, 39: 6835 - 3
Bergmann ED. Chem. Rev. 1953, 53: 309 -
4a
Page PCB.Heaney H.Rassias GA.Reignier S.Sampler EP.Talib S. Synlett 2000, 104 -
4b
Page PCB.Heaney H.Reignier S.Rassias GA. Synlett 2003, 22 -
5a
Bergmann ED.Zimkin E.Pinchas S. Recl. Trav. Chim. Pays-Bas 1952, 71: 237 -
5b
Archer TD.Balkan B.Bell PA.Brand LJ.Cheon SH.Deemo RO.Fell JB.Fillers WS.Fraser JD.Gao J.Knorr DC.Kahle GG.Leone CL.Nadelson J.Simpson R.Smith HC. J. Med. Chem. 1998, 41: 4556 -
5c
Gosain R.Norrish AM.Wood ME. Tetrahedron 2001, 57: 1399 -
6a
Bellan J.Rossi JC.Sanchez M. Tetrahedron Lett. 1976, 4621 -
6b
Shono T.Kise N.Nomura R.Yamanami A. Tetrahedron Lett. 1993, 34: 3577 -
7a
Fife TH.Hagopian L. J. Am. Chem. Soc. 1968, 90: 1007 -
7b
Lambert JB.Majchrzak MW. J. Am. Chem. Soc. 1980, 102: 3588 -
8a
Neelakantan L. J. Org. Chem. 1971, 36: 2256 -
8b
Kuhnert N.Danks TN. Green Chem. 2001, 3: 68 -
8c
Khruscheva NS.Loim NM.Sokolov VI.Makhaev VD. J. Chem. Soc., Perkin Trans. 1 1997, 2425 ; and references cited therein -
8d
Just G.Potvin P.Uggowitzer P.Bird P. J. Org. Chem. 1983, 48: 2923 ; and references cited therein - 9
Kelly R.Van Rheenen V. Tetrahedron Lett. 1973, 1709
References
(+)-(2
S
,4
S
,5
S
)-2-Isopropyl-2,3,4-trimethyl-5-phenyl-oxazolidine.
Pseudoephedrine (0.5 g, 3.0 mmol), scandium triflate (0.22 g, 0.5 mmol), and 3-methylbutanone (0.26 g, 3.0 mmol) were added to a suspension of flame dried 4 Å molecular sieves in CH2Cl2 (7.0 mL). The mixture was then heated under reflux for 48 h, allowed to cool to r.t., and solid NaHCO3 (1.0 g) added, the mixture was then stirred for a further 2 h at r.t. The solution was filtered, washed with H2O (2 × 5 mL) and the organic layer was dried over anhyd MgSO4. Solvents were removed under reduced pressure to afford a colourless oil (0.67 g, 96%). [α]D +39.0 (c 1.00, CCl4). IR (neat): νmax = 3130, 2924, 2761, 1459, 1373, 1326, 1189, 1135 cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.00
(3 H, d, J = 6.8 Hz), 1.01 (3 H, d, J = 6.9 Hz), 1.04 (3 H, d, J = 6.0 Hz), 1.29 (3 H, s), 1.83 (1 H, m), 2.24 (3 H, s), 2.50 (1 H, m), 4.33 (1 H, d, J = 8.9 Hz), 7.27-7.34 (5 H, m) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.6, 17.1, 17.4, 18.6, 33.3, 36.4, 65.8, 85.9, 98.7, 126.8, 127.7, 128.3, 140.4 ppm. MS (FAB): m/z calcd for C15H24NO [M + 1]: 234.1852; found: 234.1801.
1H NMR (400 MHz, CDCl3): δ = 1.16 (3 H, d, J = 5.9 Hz), 1.82 (3 H, s), 2.48 (3 H, s), 2.78 (1 H, m), 4.67 (1 H, d, J = 8.9 Hz), 7.35-7.47 (5 H, m), 7.20-8.58 (4 H, m) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.5, 19.3, 32.8, 65.9, 86.0, 96.8, 119.6, 122.4, 126.7, 127.9, 128.3, 136.6, 139.5, 148.1, 163.9 ppm. MS (FAB): m/z calcd for C17H21N2O [M + 1]: 269.1648; found: 269.1656.
121H NMR (400 MHz, CDCl3): δ = 1.14 (3 H, d, J = 6.0 Hz), 1.72 (3 H, s), 2.36 (3 H, s), 2.76 (1 H, m), 4.52 (1 H, d, J = 8.7 Hz), 7.30-7.67 (10 H, m) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.7, 20.7, 33.1, 65.8, 85.2, 96.2, 125.9, 126.5, 127.4, 127.7, 127.9 (2 × CH), 139.5, 145.3 ppm. MS (FAB): m/z calcd for C18H22NO [M + 1]: 268.1696; found: 268.1702.
13
(-)-(2
R
,4
S
,5
R
)-2-Methoxycarbonylmethyl-3,4-dimethyl-5-phenyl-oxazolidine-2-carboxylic Acid Methyl Ester.
Scandium triflate (0.22 g, 0.5 mmol) and but-2-ynedioic acid dimethyl ester (0.43 g, 3.0 mmol) were added to a solution of ephedrine (0.50 g, 3.0 mmol) in MeCN (10.0 mL). The mixture was then heated under reflux for 24 h, allowed to cool to r.t. and solid NaHCO3 (1.0 g) added, the mixture was stirred for a further 2 h at r.t. The solution was filtered, washed with H2O (2 × 5 mL) and the organic layer dried over anhyd MgSO4. Solvents were removed under reduced pressure to afford an orange oil, crystallisation from MeOH afforded colourless prisms (0.82 g, 89%). Mp 71-73 °C (lit.
[6a]
72 °C); [α]D -27.6 (c 1.16, CHCl3). IR (film): νmax = 3026, 2952, 1751, 1730, 1437, 1346, 1151, 1073 cm-1. 1H NMR (250 MHz, CDCl3): δ = 0.61 (3 H, d, J = 6.4 Hz), 2.28 (3 H, s) 2.83 (1 H, d, J = 16.1 Hz), 3.17-3.24 (1 H, m), 3.43 (1 H, d, J = 16.1 Hz), 3.69 (3 H, s), 3.82 (3 H, s), 5.39 (1 H, d, J = 8.1 Hz), 7.20-7.45 (5 H, m) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.3, 33.5, 41.0, 51.8, 51.9, 60.0, 83.3, 95.3, 127.7, 127.8, 127.9, 139.3, 169.8, 170.1 ppm.
CCDC 264414-264416 contain the supplementary crys-tallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44(1223)336033.