Novel Multicomponent Domino Approach to 2,5-Bifunctionalized Five-Membered Cyclic Nitrones

Abstract

Multicomponent reactions of 2,2-dimethylpenta-3,4-di­enal oxime with aldehydes and primary alcohols were studied and the optimum conditions for preparing a new family of 2,5-substituted five-membered cyclic nitrones were identified. This reaction offers direct access to the target structures in a single synthetic step. The scope and limitations of the reaction were evaluated, and all products were isolated and fully characterized.

Key words

allenes - alcohols - aldehydes - domino reactions - multicomponent reactions - nitrones

References

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• 12b

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• 24 SHELXTL, Version 5.10   Bruker AXS Inc.; Madison: 1997. 

14

For a more detailed discussion of the reaction pathway, see refs. 13a and 13b.

15

The use of an alkali metal hydroxide (KOH) as the base caused an increase in the side product 6; see ref. 13a.

16

The formation of nitrone 6 as the major product is in accordance with our previous observations of the reactivity of the allenyl oxime 1; see ref. 13a.

17

The relative conversion was determined by using diphenyl ether as an internal standard. A value corresponding to 100% conversion was obtained by analysis of the reaction performed at 80 ˚C for 3 h.

18

Zinc(II) bromide and copper(II) bromide were also tested as Lewis acid catalysts and 1,4-diazabicyclo[2.2.2]octane (DABCO) was tested as a Lewis base catalyst; the same results were obtained in each case.

19

For more-detailed information about the purity of the reaction product, see the supplementary material for this article.

20

Enolizable aldehydes were also found to be unsuitable as reaction components.

21

We also attempted the synthesis of nitrones functionalized at position 4 of the nitrone skeleton by employing substituted derivatives of allenyl oxime 1; however, none of these reactions was successful.

22

Carbon (gray), oxygen (red), and nitrogen (blue) atoms are drawn as principal ellipses (70% probability level). Hydrogen atoms are drawn as fixed-size spheres (cyan).

23

Crystallographic data for compounds 4a and 4l have been deposited with the accession numbers CCDC 822444 and 822443, respectively, and can be obtained free of charge from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: [phone];
E-mail: [e-mail]; Web site: www.ccdc.cam.ac.uk/conts/retrieving.html.