A-Acylhydrazones

A wide variety of /3-lactams are available by these routes because of the range of substituents possible in either the ketene or its equivalent substituted acetic acid derivative. Considerable diversity in imine structure is also possible. In addition to simple Schiff bases, imino esters and thioethers, amidines, cyclic imines and conjugated imines such as cinnamy-lidineaniline have found wide application in the synthesis of functionalized /3-lactams. A-Acylhydrazones can be used, but phenylhydrazones and O-alkyloximes do not give /3-lactams. These /3-lactam forming reactions give both cis and /raMS-azetidin-2-ones some control over stereochemistry can, however, be exercised by choice of reactants and conditions. 

Moreover, Kobayashi et al. introduced chiral sulfoxides into the reactions of A -acylhydrazones with allyltrichlorosilanes as highly elBcient neutral coordi-nating-organocatalysts (Scheme 10.23)." The corresponding chiral homoallylic... 

Scheme 10.23 Allylsilylations of A-acylhydrazones with sulfoxide ligands.

The literature presents a large number of examples concerning the use of known oxazolidinones as chiral auxiliaries in many kinds of reactions. Rare is the use of A-amino derivatives of oxazolidinones, which were used to synthesise new A-acylhydrazones 207. Radical addition reactions occurred with high diastereoselectivity <00JA8329>. The use of glycolate oxazolidinones 210 proved to be efficient for the enantioselective preparation of a-alkoxy carboxylic acid derivatives . Photochemical reaction of vinyl... 

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

Figure 1.32. Asymmetric hydrogenation of A-arylimines and A-acylhydrazones catalyzed by chiral Ir and Rh complexes.

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). 

Intermolecular Radical Addition to Chiral (V-Acylhydrazones 2.1 Design of Chiral A-Acylhydrazones... 

Table 1 Preparation of A -acylhydrazones from commercially available chiral oxazolidinones...

From 2-(Acyiamino)benzaldehyde and 2-(Acylamino)phenyl Methyl Ketone A -Acylhydrazones... 

Monoketones, such as acetophenone and 2-acetylpyridine, react with unsubstituted amidrazones in refluxing ethanol in the presence of a trace of hydrochloric acid to yield 1,2,4-triazolines. Increased concentration of acid causes hydrolysis of the amidrazones leading to A-acylhydrazones (Scheme 6) (73JHC353). 

Upon confronting the asymmetric carbon-nitrogen hydrogenation problem, we noted that, like a-enamides, A-acylhydrazones 32 possess an amide-like carbonyl oxygen that is similarly situated three atoms from the double bond to be reduced, and which could allow for chelation of the substrate to the catalytic Rh center. 

The reaction with A -acylhydrazones is characterized hy high regioselectivity and diastereoselectivity. ... 

A new method for the synthesis of 1,1-dialkyldiazomethanes (2.101) has been developed by Warkentin s group (Majchrzak et al., 1989). A-Acylhydrazones of ketones (2.99) are oxidized with lead tetraacetate to 2,5-dihydro-l,3,4-oxadiazoles (2.100). This intermediate undergoes a photolytic cleavage if irradiated with UV light (300 nm) at room temperature in benzene (2-45). 

Fig. 15 Self-healing via covalent bond reformation using chain exchange reactions (a) acylhydrazone equilibrium (b) reshuffling reaction of trithiocarbonates (TTC) (c) disulfide chain exchange (d) siloxane chain exchange. Reproduced with permission from [62]...

Some success has been demonstrated using Et-DuPhos-Rh complex in the asymmetric hydrogenation of A-acylhydrazone derivatives 188, which could be converted to the corresponding chiral amines (189) in a single step. ... 

Asymmetric inverse-electron-demand 1,3-dipolar cycloaddition of C,A-cyclic azomethine imines with c-rich dipolarophiles was accomplished with a high stereo-selectivity by using an axially chiral dicarboxylic catalyst (40)." The metal-free silicon Lewis-acid-catalysed 3-1-2-cycloadditions of A-acylhydrazones with cyclopentadiene provides a mild access to pyrazolidine derivatives in excellent... 

An innovative stereoselective synthesis of A-acylhydrazones via an unprecedented A-heterocyclic carbene-catalysed addition of aldehydes to diazo compounds has been presented. Enals exclusively afforded A-acylhydrazones, in yields up to 91% (Scheme 13). The observed regioselectivity was traced back to the reaction of the viny-logous Breslow intermediate via the acyl anion pathway over competing homoenolate, enol, and acyl azolium pathways. This unusual reaction profile was studied based on DFT calculations, which revealed that the reaction is under orbital control, rather than being ruled by charge. 

Alkylation and Allylation. The use of TBAT as a fluoride source for the in situ formation of pentacoordinate silicates from silanes of alkyl and allyl substituents, generating electron-rich carbon centers capable of acting as nucleophiles toward electron deficient moieties, has been well documented for over a decade. Recently, A-acylhydrazones have been shown to undergo highly diastereoselective allylations when treated with allylsilanes, TBAT, and indium(III) trifluoromethanesulfonate (eq 10). ... 

High diastereoselectivity in the allylated product is controlled through chelation of the allylfluorosilicate to the Lewis acid associated with the chiral A-acylhydrazone, causing Si-face addition. Cleavage of the N-N bond produced homoallylic amines. 

Friestad GK, Ding H. Asymmetric allylsilane additions to enantiopure A-acylhydrazones with dual activation by fiuoride and In(OTf)3. Angew. Chem. Int. Ed. 2001 40 4491-4493. 

---