Oxazolinone mechanism

Scheme 4.15 Proposed mechanism for the synthesis of iV-methyl oxazolinones from oximes.

Treatment of an a-amino acid with an anhydride in the presence of pyridine, known as the Dakin-West reaction,[1431 gives access to a racemic a-amido ketone.1 44 1451 The mechanism involves formation of an oxazolinone (98)J146 In the modified Dakin-West reaction, the oxazolinone is reacted with an acid chloride (Scheme 33)J136 139] Due to the rapid epimer-ization of the oxazolinones, a diastereomeric mixture of product 99 is obtained. No detailed protocol has been published so far for the modified Dakin-West synthesis applied to (oxomethyleneamino) peptides, but the procedure is adapted from that already reported for (oxomethylene) peptides containing the tp[CO-CH2] link.1147 ... 

Dimethylamino-2,2-dimethyl-2//-azirine (27) and 4-isopropyl-2-trifluo-romethyl-5-oxazolinone (28) gave 5-dimethylamino-3-isopropyl-6,6-di-methyl-3,6-dihydro-2(l//)-pyrazinone (29) (MeCN, reflux, N2, 1 h 60% a rational mechanism was suggested) 944 analogues, like 3-allyl-5-dimethy-lamino-6,6-dimethyl-3-phcnyl-3,6-dihydro-2(l//)-pyrazinone (44%),958 were made similarly.944 958... 

The basis for exploring heterocycles as inhibitors of HLE came from the discovery that some heterocycles, for example, sultones (12-1, Table 2.12) [174], oxazolinones (12-2) [175], or lactones (12-3) and (12-4) [176], were alternate substrates for serine proteinases. The proteinases reacted with these compounds to (a) cleave the heterocyclic ring, (b) form an intermediate acyl-enzyme and (c) then hydrolyze the acyl-enzyme by the normal catalytic mechanism to release active enzyme and the ring-opened heterocycle. 

A Dakin-West reaction on plant scale is demonstrated by elaboration of a modified procedure avoiding uncontrolled release of carbon dioxide. It seems to be generally accepted that the mechanism involves dehydrative formation of an azlactone (oxazolinone), which is then C-acylated (in equilibria with G-acylation), undergoes ring-opening hydrolysis, and then decarboxylates to form the acylamino ketone. Pyrimidine ring formation is achieved in a simple one-pot reaction, which is followed by a simple isomerization. Laboratory experiments had made clear that the mechanism... 

It should be pointed out that some Pd-catalyzed reactions of allenes with nucleophiles proceed by a different mechanism. The mechanistically interesting intramolecular reaction of allenylcarbamate 105 with acrolein afforded the oxazolinone 106 in the presence of Pd(OAc)2 and LiBr. This reaction is promoted by Pd(II), not by Pd(0) [31]. Unlike the Pd(0)-catalyzed reactions surveyed in the above section. 

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