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

Abstract

N,N-Dimethylhydrazones of propenal-and 2-methylpropenal and their derivatives and homologues (vinylogous azaenamines) 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 w-position of the p-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 d 3 -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. The isoelectronic exchange of C1 in enamines I 3 by nitrogen formally leads to aldehyde hydrazones III (Scheme 1). Such hydrazones can be formally regarded as aza-enamines. Some time ago, we could demonstrate that besides this formal connection, also real relations exist in the reactivities of both structural classes. Both react with electrophiles E + , the enamines at C2 to yield II and the aldehyde hydrazones at the azomethine C-atom giving rise to IV. Consequently, the azomethine carbon corresponds to the enamine C2 carbon atom. Both owe this property to the conjugative interaction between the electron-donating dialkylated nitrogen atom and the carbon-carbon and carbon-nitrogen double bonds in the sense of mesomeric structures I¢ and III¢. The aldehyde hydrazones are N,Ndialkylated, for example, as in the pyrrolidino, piperidino, or dimethylamino derivatives, because they proved to be the most effective electron donors in enamine chemistry. 3 Examples for this behavior of aldehyde N,N-dialkylhydrazones are the acylation with the Vilsmeier reagent 4a-d,f and trifluoroacetic anhydride, 5a,b the carboxylation with sulfonyl isocyanates, 4b,e,6a-d as well as the alkylation with electrophilic olefins (Scheme 1). 7a-cThe reactions occur contrary to the normal polarity of the imino structural element as expressed in III¢¢; thus, such hydrazones proved to react as umpoled d 1 -nucleophilic aldehyde derivatives. Moreover, they are neutral acyl anion equivalents and thus differ from these strongly alkaline reagents. 8a-c This aza-enamine principle is also applicable to vinylogous aldehyde hydrazones. Consequently the dimethylhydrazones of the a,b-unsaturated aldehydes V are attacked by electrophiles at the vinylogous C3-position leading to VI (Scheme 2). This represents an umpolung of the Michael acceptor reactivity. Therefore, these neutral d 3 -nucleophilic building block...

The Recycling of Substandard Rocket Fuel N,N-Dimethylhydrazine via the Involvement of Its Hydrazones Derived from Glyoxal, Acrolein, Metacrolein, Crotonaldehyde, and Formaldehyde in Organic Synthesis

“…Hydroxyl and butyl groups (structures 106 and 108, respectively) were introduced by reacting with butyl alcohol in the presence of ammonium chloride [85] (Figure 18). The DMHA chain lengthening described in publication [90] (Figure 19) is also of interest in organic synthesis. N,N-dimethylformiminium hydrochloride 114 in absolute dimethylformamide (DMF) was used as the electrophile.…”

“…The DMHA chain lengthening described in publication [90] (Figure 19) is also of interest in organic synthesis. N,N-dimethylformiminium hydrochloride 114 in absolute dimethylformamide (DMF) was used as the electrophile.…”

“…N,N-dimethylformiminium hydrochloride 114 in absolute dimethylformamide (DMF) was used as the electrophile. The authors of [90] proposed that DMHA adds to N,N-dimethylformiminium 114 (Figure 19) through its tautomeric form 113, with the hydrogen being replaced by the methylene group of intermediate 115 located at the dimethylamino group. When one equivalent of N,N-dimethylformiminium 116 was added to DMHA, salt 117 was formed.…”

“…In the first case, tetrahydroquinoline 128 was synthesized through the indium (III) chloride-catalyzed reaction of DMHM with Schiff base 125 in acetonitrile at room temperature. In the second case, the authors of [90] elucidated the formation of a tricyclic structure 132 from arylamine 135. This was explained by a cascade process involving several steps.…”

Ligand-Controlled Diastereodivergency in Propargylic Alkylation of Vinylogous Aza-Enamines: Construction of 1,3-Stereocenters

“…N , N -Dialkylhydrazones of α,β-unsaturated aldehydes, commonly known as vinylogous aza-enamines, although known for a few decades and employed initially as azadienes in cycloaddition reactions, their application as polarity reversed (umpoled) nucleophile first appeared in 2010 . Despite synthetic versatility of the aza-enamine functionality, only a couple of reactions involving vinylogous aza-enamines have been reported since then .…”