Hydrazones acyl anion equivalents

In 2008, the same group employed chiral dicarboxylic acid (R)-5 (5 mol%, R = 4- Bu-2,6-Me2-CgHj) as the catalyst in the asymmetric addition of aldehyde N,N-dialkylhydrazones 81 to aromatic iV-Boc-imines 11 in the presence of 4 A molecular sieves to provide a-amino hydrazones 176, valuable precursors of a-amino ketones, in good yields with excellent enantioselectivities (35-89%, 84-99% ee) (Scheme 74) [93], Aldehyde hydrazones are known as a class of acyl anion equivalents due to their aza-enamine structure. Their application in the field of asymmetric catalysis has been limited to the use of formaldehyde hydrazones (Scheme 30). Remarkably, the dicarboxylic acid-catalyzed method applied not only to formaldehyde hydrazone 81a (R = H) but also allowed for the use of various aryl-aldehyde hydrazones 81b (R = Ar) under shghtly modified conditions. Prior to this... 

Thiamine-catalyzed transformations are reversible, thus TV,/V-dialkyl hydrazones were selected as alternative acyl anion equivalents that were reported to react with electrophiles without acidic activation.41 One especially reactive example, formaldehyde hydrazone resin 13, was constructed from polymer-supported hydrazines and was employed in the first polymer-supported, uncatalyzed acyl anion additions (Fig. 8).38 As test substrates, nitroalkenes (as Michael acceptors) and activated aldehydes were selected. Reactivity of these acyl anion equivalents depended critically not only on the nature of the starting hydrazine, but also on the protocol for hydrazine formation. 

Three approaches leading to 8 were considered (Figure 3.6.9) Following the biosynthetic pathway directly, polymer-supported thiamine 9 was constructed (path A) and could lead via crossed acyloin couplings to the target structure. Polymer-supported hydrazones 10 were reported to add directly to aldehydes in a non-catalyzed Umpolung reaction (path B) with results reported in due course. Finally, phosphine ylides 11 were investigated as polymer-supported acyl anion equivalents (path C). 

The anions of hindered hydrazones allow the introduction of electrophiles at the a-position, thus functioning as acyl anion equivalents after isomerization back to a hydrazone and hydrolysis.For example, the r-butylhydrazone of acetaldehyde gives phenylacetone following the sequence of reactions shown in equation 44. 

Baldwin has shown that monoalkyl hydraztmes may be used as acyl anion ( RCO ) or a-amino anion equivalents ( CH2NH2 )- An example of Ae former is shown in Scheme 37. Note that the isomerizadon step (26 27) is necessary to avoid reversion to the parmt hydrazone and ketone. ... 

Imidazolidine-derived organolithium compounds 468 have been prepared by deprotonation of the corresponding IV-acylated imidazolidines with two equivalents of s-BuLi at — 78 °C. The best results have been obtained with the fraws-l,2-diaminocyclohexane-derived imidazolidine 472, so its anion 473 reacted with different electrophiles to give compounds 474 in moderated yields, which gave the expected hydrazones 471 as described above (Scheme 124)676,677. Other imidazolidines suffered deprotonation at the 4-position... 

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