Azlactone initiators

Patent Ring-Opened Azlactone Initiators for Nitroxide-Mediated... 

The preparation of the less stable isomer (53b) of the oxazolone 53a involves a rather tedious procedure. It has been reported that 53a is rapidly isomerized to 53b in 48% hydrobromic acid saturated with gaseous HBr. In this way four azlactones have been converted into their isomers.It has been established, moreover, that the isomerization is radical-initiated and does not involve a carbonium ion intermediate. The isomerization can be reversed by pyridine. ... 

Since amines react more readily than alcohols in noncatalyzed reactions with anhydrides, the reaction is more difficult and initially required stoichiometric catalyst loadings [107], but could be performed in a catalytic sense with an O-acylated azlactone as acylating agent, which does not react with a benzylic amine at —50°C, but is capable of acylating the catalyst [108, 109]. Depending on the buUdness of the substrate, selectivities ranged from S = 11 to 27 (s = [ enantiomer l]/[ enantiomer 2])-... 

Another method of obtaining unsaturated azlactones is through p-phenylserine [Ser(p-Ph)] derivatives. This method was initially introduced by BergmannJ56 The method involves conversion of (3-phenylserine derivatives 11 into the corresponding APhe azlactones 12 by treatment with an acetic anhydride/sodium acetate solution (Scheme 4). This has remained as one of the most popular methods of synthesis. 

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... 

Michael addition to alkenyl azlactones is not limited to mercaptans, but also occurs to a significane extent with secondary amines. This was first observed upon attempted reaction of azlactone with Jeffamlne CD-2000 (Texaco Chemical, Inc.) (Scheme 9). Initially, no reaction was observed at room temperature over two days time. However, heating the mixture at 50-70°C overnight resulted in clean conversion to the corresponding bisazlactone. As might be expected, the source of the azlactone appears to have no effect upon the course of this reaction. 

A new approach to a-amino acid containing a geminal bisphosphonate moiety (578) has been developed. A two-step reaction sequence utilised the Michael addition of a-substituted azlactones (576) to a vinylidene bisphosphonate (577) followed hy azalactone ring opening under acidic conditions (Scheme 166). Initial attempts to develop an enantioselective version of this reaction have been also demonstrated. ... 

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