Unsaturated 5 -oxazolones, ring opening preparation

Other alcohols ring-open unsaturated oxazolones including glycerol that was used to prepare monoglycerides of acylamino acids.In addition, alcoholysis with 3,4,4-trifluorobut-3-enol leads to amino acid fluorobutenyl esters that are used as pesticides.Finally, (dimethylamino)ethanol and other amino alcohols have also been used to obtain the corresponding aminoalkyl esters. 

The mechanism of the aminolysis and the electronic effects of substituents at C-2 or C-4 on the kinetics of amide bond formation have been studied. In some cases, ring opening with amines occurs with partial isomerization of the exocyclic double bond. However, with more hindered compounds, such as unsaturated oxazolones derived from ketones, ring opening is stereospecific.Ring opening using diamines has also been described. Selected examples of dehydroamino acid amides prepared by aminolysis of unsaturated 5(4//)-oxazolones are shown in Table 7.40 (Fig. 7.51). 

Therefore, suitable unsaturated oxazolones can be used as intermediates to prepare dehydropeptides wherein the synthetic strategy used will depend on the position of the double bond in the final compound. If the double bond is located in the N-terminal amino acid, ring opening of the oxazolone 516 with the appropriate amino acid or peptide generates the desired dehydropeptide 517 directly. 

It is well known that hydrogenation of dehydroamino acid derivatives derived from ring opening of unsaturated 5(4H)-oxazolones affords new racemic amino acids and, in some cases, enantiomerically pure compounds. On the other hand, a number of attempts have been made to hydrogenate the double bond of the unsaturated oxazolone itself. For example, 4-benzyl-2-methyl-5(4//)-oxazolone was prepared from 4-benzylidene-2-methyl-5(4H)-oxazolone using Raney Ni as a catalyst. This process is reported to be a general procedure to prepare saturated oxazolones directly (Scheme 7.194). 

Both reactions have been utilized to prepare heterocyclic compounds such as pyrazoles 681 (X = A -Ph) and isoxazoles 681 (X = O) as shown in Scheme 7.214. " Starting from an unsaturated 5(4//)-oxazolone 677, either a cycloaddition-ring-opening reaction sequence (677 678 680) or a ringopening-cycloaddition reaction sequence (677 679 680) affords the same product. 

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