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Synthesis 2010(20): 3556-3568  
DOI: 10.1055/s-0030-1258194
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Aza-enamines XI. [¹] Vinylogous Aza-enamines as Neutral d³-Nucleophiles: Aminomethylations of N,N-Dimethylhydrazones of α,β-Unsaturated Aldehydes

Matthias T. Grabowskia,, Karol Nowosinskia, Dieter Lentzb, Rainer Brehme*a, Christoph A. Schalley*a
a Institut für Chemie and Biochemie der Freien Universtät Berlin, Takustraße 3, 14195 Berlin, Germany
Fax: +49(30)83855817; e-Mail: schalley@chemie.fu-berlin.de;
b Institut für Chemie and Biochemie der Freien Universtät Berlin, Fabeckstr. 34-36, 14195 Berlin, Germany
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Publication History

Received 31 March 2010
Publication Date:
09 August 2010 (online)

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Abstract

N,N-Dimethylhydrazones of propenal- and 2-methyl­propenal and their derivatives and homologues (vinylogous aza-enamines) were allowed to react with N,N-dimethylformiminium chloride in moisture-free dimethylformamide to yield singly, doubly, and even triply aminomethylated products. They can be easily separated and characterized as crystalline hydrochlorides. The reaction takes place at the ω-position of the π-system. This is a consequence of the conjugative interaction of the electron-donating aminohydrazone group with the double bond system in analogy to the enamines. The formation of dialkylhydrazones from unsaturated aldehydes thus causes the umpolung of the formerly electrophilic d³-building blocks into a nucleophile. Depending on the reaction conditions and confirmed by crystal structures and 2D NMR experiments, control can be exerted over the degree of substitution: Up to trisubstituted products were obtained for the 2-methylpropenal derivative. The hydrochlorides can be easily deprotonated to yield the free aminohydrazone bases. The back-conversion of the aminohydrazones into the corresponding amino aldehydes is possible under acidic conditions.

Key words

hydrazones - electrophilic substitution - nucleophilic addition - amino aldehydes - umpolung

1

For Aza-enamines part X, see ref. 4d.

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1

For Aza-enamines part X, see ref. 4d.

2

Present address: Institut für Chemie der Technischen Universität Berlin, Straße des 17. Juni 135, 10623 Berlin, Germany.

14

The synthetic procedures are described in references 5b, 9, 15, 18-21, which are cited in the text when the corresponding hydrazone is first mentioned.

17

The ¹H NMR shift of the azomethine proton depends on the protonation state of the hydrazone amino group. For example, the azomethine signal of unprotonated 3-(4-nitrophenyl)prop-2-enal dimethylhydrazone (20) appears at 7.07 ppm, while it experiences a significant downfield shift to 8.73 ppm upon protonation to 20˙HCl.

25

Crystallographic data (excluding structure factors) for the structures reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication numbers CCDC-725902 [(Z)-6˙HCl], CCDC-725903 [(Z)-10˙4HCl], CCDC-725904 [(E)-12˙2HCl], CCDC-725901 [(Z)-21˙HCl] and CCDC-780812 (27). Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [Fax: +44(1223)336033; e-mail: deposit@ccdc.cam.ac.uk].