Azlactones tables

Subsequently, a number of additional multiazlactones were synthesized from various polythiols and alkenyl azlactones (Table 1). In those cases where the addition of a catalyst was required, ethanesulfonic acid was found to be quite satisfactory. With the exception of bisazlactone 4 (a low melting solid), all of these multiazlactones were fluid materials. 

Table 1. Porous properties and enzymatic activities of monolithic poly(2-vinyl-4,4-dimethyl-azlactone-co-acrylamide-co-ethylene dimethacrylate) reactors3... 

Whereas preparation of a-amino acid derivatives by asymmetric allylation of an acyclic iminoglycinate gave a modest enantioselectivity (62% ee) in an early investigation [189], the use of conformationally constrained nucleophiles in an analogous alkylation resulted in high selectivities (Scheme 8E.43) [190], With 2-cyclohexenyl acetate, the alkylation of azlactones occurred with good diastereomeric ratios as well as excellent enantioselectivities. This method provides very facile access to a variety of a-alkylamino acids, which are difficult to synthesize by other methods. When a series of azlactones were alkylated with a prochiral gem-diacetate, excellent enantioselectivities were uniformly obtained for both the major and minor diastereom-ers (Eq. 8E.20 and Table 8E.12). 

TABLE 8E.12. Alkylations of Azlactones with Cinnamyl 1,1 -Diacetate... 

N-acyldehydrodipeptides were readily prepared either by the condensation of N -acyldehydro-a-amino acids with a-amino acid esters or by the reaction of the azlactones of dehydro-a-amino acid with a-amino acid esters (eq. 1). Asymmetric hydrogenation of the N-acyldehydrodipeptides thus obtained (eq. 2) was carried out by using rhodium complexes with a variety of chiral diphosphines such as -Br-Phenyl-CAPP (3), Ph-CAPP (3), (-)BPPM (4), (+)BPPM (4), (-)DIOP ( ), (+)DIOP ( ), diPAMP (6), Chiraphos (7), Prophos (S), BPPFA (9) and CBZ-Phe-PPM (Fig. 1)(10). The chiral catalysts were prepared in situ from chiral diphosphine ligand with [Rh(NBD)2l -CIO4 (NBD = norbomadiene). Typical results are summarized in Tables I-V. 

As presented in some detail by Gingrich and Baum (see their Table 4.31 and Scheme 4.51) azlactones react with ot,p-unsaturated imines to give ot-pyridones. Sandhu and co-workers continued the studies in this area, and they now view this reaction as involving initial electrophilic attack on the azlactone (munchnone) followed by cyclization to an ot-pyridone, rather than prior ring-opening to the corresponding ketene tautomer, as was originally proposed (Table 4.1). With azlactone 52 and A-aryl cinnamaldehyde anils 53, in the presence of acetic anhydride, the 4-substituted azlactones 54 are isolated (Fig. 4.15). Dalla Croce... 

TABLE 4.1. REACTION OF AZLACTONES WITH ot,p-UNSATURATED IMINES... 

This group also found that azlactones react with vinyl phosphosphonium salts to give A -unsubstituted pyrroles 224 (Table 4.15). Further support for the regio-chemistry comes from the reaction of 2-carboxyvinyltriphenylphosphonium bromide 225 with munchnones 149 to give the pyrroles shown (Fig. 4.80). With azlactone 226, the dihydropyrrole 227 is isolated. 

TABLE 4.15. 1,3-DIPOLAR CYCLOADDITION REACTIONS OE MUNCHNONES (AZLACTONES) AND VINYL PHOSPHONIUM SALTS"... 

TABLE 4.1 REACTION OF AZLACTONES WITH a,p-UNSATURATED IMINES, 483... 

The overall reaction of alkenyl azlactones (J ) and amine-terminated oligomers -6 is depicted in Equation 1, with actual reactants listed in Table 1. 

Table 1. Multlazlactones from Polythiols and Alkenyl Azlactones... 

This observation, however, has not solved the entire problem since BF 0Et2 also appears to be very efficient in catalyzing hydrolysis of the azlactone ring by reaction with adventitious water. Further studies in the catalyst area will be necessary. Table 2 lists our results to date with polyoxyalkylenebismercaptans, indicating estimated purity (by H-NMR) of the bisazlactone products and their corresponding viscosities. 

To gain further insight into the reactions of alkenyl azlactones with secondary amines, reaction of 2 with a variety of simple amines was studied. Table 3 lists the results as the ratio of Michael addition to ring-opening as estimated by 100 MHz H-NMR. As can be seen from the... 

Kobayashi et al. also applied the catalyst to asymmetric 1,4-addition reactions of azlactones with acrylates [66]. The active a-proton of the azlactone (5(4H)-oxazolone) skeleton showed a low pKa value compared to that of the alanine Schiff bases, because the anion formed is stabilized via enol formation and aromatization. After 1,4-addition reactions with acrylates, the 2-substituted glutamic acid derivatives formed could be obtained via hydrolysis using a weak acid. It was found that Pybox 3 prepared from alaninol derivatives was effective for this reaction. The desired products were obtained in good yields with good enantios-electivities. Several amino acid derivatives containing aUcyl chains in the a-position were screened, and the leucine derivative (R = Bu) showed the best enantio-selectivity in this reaction (Table 16, entry 8). 

Table 16 Catalytic 1,4 additioj, reactirais of azlactones with acrylates using a chiral Pybox-...

Those azlactones reported in the literature up to and including the 1944 Chemical Abstracts are listed in the following tables. Many of them were prepared as intermediates, and the substances to which they were converted are listed along with them. 

TABLE Continued Unsatubated Azlactones C. S-Phenyl-4-pyrrolalr5-oxwiolones... 

Nomenclature. The names by which the compounds are listed in the table are those which emphasize the parent acid, in order to facilitate ready location. Thus benzoic ester is used instead of ethyl benzoate. Ethyl esters are referred to simply as ester all other esters are specifically designated. Cyclic anhydrides, lactones, and azlactones are listed under the parent acid rather than under heterocyclic compounds. 

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