Efficient Base-Catalyzed 5-exo-dig Cyclization of Carbonyl Groups on Unactivated Alkynyl-Quinolines: An Entry to Versatile Oxygenated Heterocycles Related to the Furoquinoline Alkaloids Family
Thomas Godet, Johann Bosson, Philippe Belmont* Université Claude Bernard Lyon I, UMR CNRS 5181, Méthodologie de Synthèse et Molécules Bioactives, Bâtiment CPE, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne Cedex, France Fax: +33(4)72432963; e-Mail: belmont@cpe.fr;
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Received
4 August 2005 Publication Date: 21 October 2005 (online)
An efficient 5-exo-dig cyclization was observed when TMS-protected alkynyl-quinolines bearing a carbonyl group were submitted to a mixture of an alcohol (alkyl-OH, diol, amino alcohol) with an inorganic base (K2CO3). The cyclization process seems to go through the deprotection of the TMS group prior to the cyclization step. The dihydrofuroquinoline derivatives formed are structurally related to the well-known furoquinoline alkaloids family. The scope and limitations of this reaction have also been studied with diverse bases and various alkynyl and carbonyl derivatives.
In this letter we do not refer to the addition/cyclization of alcohols or acids on alkynes which has been also extensively studied. Some insight of this work can be found in some recent publications. For alcohols and phenols see:
1dAntoniotti S.
Genin E.
Michelet V.
Genêt J.-P.
J. Am. Chem. Soc.
2005,
127:
9976
For alternative procedures with base-promoted intramolecular addition reactions of nucleophiles (alcohol and nitrogen) to an unactivated triple bond, see:
11aPadwa A.
Krumpe KE.
Weingarten MD.
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1995,
60:
5595
The exo-methylene J(CH2) coupling constant was in accordance with geminal coupling value, i.e. 2.3 Hz and in the 13C NMR DEPT experiments, a signal was found for the exo-methylene CH2 carbon center which could not exist in a 6-endo-dig product (Scheme
[4]
).
The 3-D structure was confirmed by comparison with the NMR data from the non-deuterated derivative 3. The silyl species D3C-OSi(CH3)3 was also identified by 1H NMR from a sample of commercially available H3C-OSi(CH3)3, in CD3OD.
Column chromatography was performed on silica gel (mixture of cyclohexane-EtOAc) adding 0.6% of Et3N. If care is not taken during purification, we have observed for compounds derived from aldehyde 1, the formation of a quinoline bearing an aldehyde function in position 3 and a methyl ketone in position 2 (see Scheme
[5]
below). This compound results from the hydrolysis of the hemiacetal. The presence of the methyl ketone confirms the formation of a 5-exo-dig product in all cases since a 6-endo-dig cyclization would have produced the formation of a quinoline bearing two aldehyde groups.
