Acylhydrazones hydrazones

Imines and related compounds containing a carbon-nitrogen double bond C=N (hydrazones, acylhydrazones, oximes) present the very attractive feature of being double dynamic entities capable of undergoing both ... 

A -Acylhydrazones of 1,3-dicarbonyl compounds can exist in three tautomeric forms enhydrazine 75A, hydrazone 75A, and 5-hydroxypyrazoline... 

Nonoxidative cyclization of acylhydrazones in acetic anhydride yields 4-acetyloxadiazolines, as in the conversion of hydrazone (96f R = 2-benzthiazolyl) into oxadiazoline (90b) <89MI 406-03). Hydrazones derived from tetra-O-acetyl-D-arabinose cyclized (Ac20/ZnCl2) to oxadiazoles pos-... 

For A-acylhydrazones containing an N—H group in the heterocycle moiety, 66A and B (85KGS774), 67A and B (84MI1), the open-chain and cyclic isomers have been isolated. The gas-chromatographic behavior of the latter isomeric hydrazones was studied and the ability of this method to allow the distinction and determination of the isomers was shown (84MI1). 

Ketone-derived chiral /V-acylhydrazones may also be prepared by direct condensation with /V-aminooxazolidinone 2a (Table 2) [45, 49]. Mixtures of E/Z isomers were usually obtained, although ketone /V-acylhydrazones 9d and lOd, with highly branched tertiary butyl (7-Bu) substituents, were formed as single isomers. Pyruvate-derived hydrazone (E)-11 was formed with high selectivity, and the major isomer was readily separated from its minor (Z)-isomer by flash chromatography [45], Others have recently used these amination and condensation... 

The first test of the chiral /V-acylhydrazones was in tin-mediated radical addition [47,48]. Addition of isopropyl iodide to propionaldehyde hydrazone 3a was chosen for initial screening (Scheme 2). Using the tin hydride method with triethylborane initiation [51, 52] (Bu3SnH, Et3B/02), with InCl3 and ZnCU as Lewis acid additives, desired adduct 13a was obtained with high diastereoselectivity. In contrast, 13a was produced with poor selectivity (diastereomer ratio, dr 2 1) in the absence of Lewis acid. 

Diastereoselectivity in radical additions to hydrazones 3 and 7 proved to be quite promising, with diastereomer ratios ranging from 93 7 to 99 1 (Table 3) [47]. In search of optimal stereocontrol, substituents on the oxazolidinone moiety were varied. Thus, isopropyl radical additions to several /V-acylhydrazones 3a-3e were compared for stereoselectivity (Scheme 3). High diastereoselectivities were observed in all adducts 13a-13e, although a rigorous measurement was not obtained on 13c. All of the auxiliaries impart stereocontrol suitable for practical synthetic application [48],... 

A variety of aldehyde hydrazones were screened [24b]. Branching at a saturated a carbon was detrimental in the tin mediated radical additions, but an aromatic benzaldehyde hydrazone 12 offered some success, with yields ranging from 30 to 83% (Table 2.3, entries 5 8). With the exception of 8a, which decomposed under the reaction conditions, the reactions were quite dean. Even in the examples with lower yields, the mass balance after recovery of the hydrazone precursor was generally 80 90%, demonstrating the excellent chemoselectivity of the reactions of radicals with N acylhydrazones. We were delighted to find that the radical additions had occurred with excellent stereocontrol in all secondary and tertiary radical additions to hydrazones 8 and 12 (Table 2.3), with diastereomer ratios ranging from 93 7 to 99 1 [24]. 

Next, the effects of varying the stereocontrol elements on the oxazolidinone moiety were assessed, with the main goal to examine the change in diastereoselectivity. Without optimizing for yield, isopropyl radical additions to several N acylhydrazones 8a 8e (See Scheme 2.1 for structures) were compared for stereo selectivity (Table 2.4). Although the measurement was not available for 8c, all auxiliaries gave very high diastereoselectivity in addition of isopropyl radical to propionaldehyde hydrazone [24b]. 

For the y amino acid 44 (Figure 2.5), phenylacetaldehyde N acylhydrazone 48 (Scheme 2.7) was employed as the radical acceptor. Mn mediated addition of difunctional iodide 49a (5 equiv) proceeded in 56% yield, affording SOa as a single diastereomer [39]. Recently, we found that the unprotected alcohol 49b couples with hydrazone 48 in 79% yield, using a modest excess (3.5 equiv) of the iodide. Considering that typical intermolecular radical additions often require large... 

Monosubstituted hydrazones of aldehydes (19) are oxidised by lead tetraacetate to afford A/-acetyl AT-acylhydrazones.25-77 The reaction proceeds via a A -hydrazone intermediate which undergoes a ligand coupling reaction to give an hydrazonyl acetate (20) which then rearranges to the final product. Monosubstituted hydrazones of ketones (22) react with lead tetraacetate to give a-azoacetates (23). ... 

H.J. Bestmann has prepared the phosphazine of TFAE from 18 and triphenyl phosphine. This compound is hydrolyzed by ZnCl2/H20 to give the parent hydrazone 22 and it can be transformed to the corresponding tris carbonyl compound using HN02 (ref. 41). In analogy to the studies by H. Neuenhoffer, we have N-acylated 22 by acid anhydrides to obtain crude N-acylhydrazones 211 in about 50 % yield (Scheme 46). 

Acylhydrazones, R CH=N-NHCOR , undergo stereoselective Mannich reactions with silyl ketene acetals to give j8-hydrazido esters, using activation by a chiral silicon Lewis acid. Alternatively, the use of silyl ketene imine gives a /3-hydrazido nitrile. Enantioselective (5)-l-amino-2-methoxymethylpyrrolidine (SAMP) hydrazone alkylation of aldehydes and ketones is the subject of a computational study, providing a useful screening method for possible new candidates. " ... 

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