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Synlett 2009(17): 2821-2824  
DOI: 10.1055/s-0029-1217984
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Bicyclic Pyridones via Cyclocondensation of Heterocyclic Ketene Aminals with β-Ketoester Enol Tosylates

Sheng-Jiao Yan, Yan-Fei Niu, Rong Huang, Jun Lin*
Key Laboratory of Medicinal Chemistry for Natural Resource (Yunnan University), Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, P. R. of China
Fax: +86(871)5033215; e-Mail: linjun@ynu.edu.cn;
Further Information

Publication History

Received 8 July 2009
Publication Date:
24 September 2009 (online)

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Abstract

A series of novel bicyclic pyridones were easily prepared by cyclic condensation of heterocyclic ketene aminals with β-keto ester enol tosylates in the presence of a base to give products in excellent yields (80-95%).

Key words

pyridones - cyclocondensation - heterocyclic ketene aminals - β-keto ester enol tosylates

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General Procedure for the Cyclocondensation Reaction
A 50 mL round-bottom flask was charged with β-keto ester enol tosylates 2 (1 mmol), 1,4-dioxane (10 mL), and Et3N (3 mL), then the solution was added to HKA 1 (1 mmol), and the solution was refluxed. The resulting solution was stirred for 3-14 h until the β-keto ester enol toslates 2 were completely consumed. The mixture was quenched by the addition of H2O (50 mL). The reaction mixture was filtered off, and the residue was washed with H2O to give a crude product that was recrystallized by EtOH or acetone to form the final products 4-6.
Compound 4d: yellow solid; mp 184-187.5 ˚C. IR (KBr): 3366 (NH), 3079 (C=CH), 1679 (C=O), 1602 (C=O), 1558 (C=C), 1324 (CN), 1165 (CF) cm-¹. ¹H NMR (500 MHz, DMSO-d 6): δ = 3.68 (t, J = 9.2 Hz, 2 H, CH2), 4.11 (t, J = 9.1 Hz, 2 H, CH2), 6.00 (s, 1 H, CH=), 7.56-7.79 (m, 5 H, ArH, NH). ¹³C NMR (125 MHz, DMSO-d 6): δ = 42.6 (NCH2), 43.7 (NCH2), 91.8 (CCOAr), 104.3 (CHCO), 122.5 (q, J = 211.3 Hz, CF3), 128.5 (2 × CHar), 131.1 (2 × CHar), 137.0 (Car), 137.8 (Car), 140.0 (q, J = 30 Hz, CCF3), 154.4 (C=CCOAr), 159.0 (C=O), 190.2 (COAr). HRMS (TOF
ES-): m/z calcd for C15H9ClF3N2O2 [M - H+]: 341.0310; found: 341.0308.

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CCDC 738457 contains the supplementary crystallographic data for compound 4d. These data can be obtained free of charge from The Cambridge Crystallographic Data Center via www.ccdc.cam.ac.uk/data_request/cif.