Stereoselective Synthesis of Functionalized γ-Amino Esters: Azetidinium Salts and Epoxy Esters

Organic Letters

Volumn 4, Issue 8, 2002, Pages 1299-1301

  Concellón, José M ^a   Riego, Estela ^a   Bernad, Pablo L ^a  

^a UNIVERSITY OF OVIEDO   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; AZETIDINE DERIVATIVE; DYES, REAGENTS, INDICATORS, MARKERS AND BUFFERS; EPOXIDE;

ARTICLE; CHEMISTRY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; STEREOISOMERISM;

AMINO ACIDS; AZETIDINES; EPOXY COMPOUNDS; INDICATORS AND REAGENTS; MAGNETIC RESONANCE SPECTROSCOPY; STEREOISOMERISM;

EID: 0037129404     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol025590f     Document Type: Article

References (31)

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21. Concellón, J. M.; Bernad, P. L.; Riego, E.; García-Granda, S.; Forcén-Acebal, A. J. Org. Chem. 2001, 66, 2764-2768.
22. 13C NMR: δ 171.5, 139.2, 128.7, 127.9, 126.6, 75.9, 60.3, 55.6, 55.0, 49.5, 38.9, 13.6, 6.0.
23. Formation of azetidinium salts starting from halohydrins has been also observed in similar substrates: (a) Reference 7. (b) Concellón, J. M.; Bernad, P. L.; Pérez-Andrés, J. A. J. Org. Chem. 1997, 62, 8902-8906.
24. Formation of azetidinium salts starting from halohydrins has been also observed in similar substrates: (a) Reference 7. (b) Concellón, J. M.; Bernad, P. L.; Pérez-Andrés, J. A. J. Org. Chem. 1997, 62, 8902-8906.
25. 2/EtOAc to give pure compounds 3. When epoxy esters 4 were isolated, flash column chromatography over silica gel (hexane:triethylamine = 50:1) provided pure compounds 4e-g.
26. Representative procedure for the synthesis of epoxy esters 4a-c: To a -85 °C stirred solution of lithium diisopropylamide (5.5 mL of solution 0.3 M in THF, 1.65 mmol) was added dropwise a solution of ethyl acetate (0.14 mL, 1.5 mmol) in dry THF (1 mL). After stirring for 10 min, a solution of the corresponding 1-aminoalkyl chloromethyl ketone 1 (1 mmol) in dry THF (2 mL) was added dropwise at -78 °C. The reaction mixture was stirred at the same temperature for 1 h, and then water (4 drops) was added. After stirring for 15 min at -40 °C, NaH (0.24 g, 10 mmol) was added, and the mixture was allowed to warm to room temperature for 20 min and carefully quenched with water (10 mL). Usual workup provided crude compound 4a-c. Flash column chromatography over silica gel (hexane:ethyl acetate = 15:1) afforded pure compounds 4a-c.
27. When the aldol reaction was hydrolyzed at room temperature, a mixture of 4 and an α,β-unsaturated lactone derived from 4 was isolated. See: Concellón, J. M.; Riego, E.; Bernad, P. L. Org. Lett. 2002, 4, 1303.
28. The optical purity was determined by chiral HPLC analysis of the α,β-unsaturated lactone derived from 4c. See ref 15.
29. 4). filtered, and concentrated in vacuo to provide compound 5a.
30. The relative configuration of the chiral center formed from the enolate in the major diastereoisomer 3d was determined by an NOESY experiment on a 3d derivative. See ref 15.
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