Unsaturated 5 -oxazolones, ring opening reactions

Classical ring-opening reactions of unsaturated oxazolones are the most well studied reactions and generate a wide variety of interesting products. However, reactions of the exocyclic double bond have also been investigated and open the way to a tremendous variety of new possibilities. 

Organophosphorous compounds have also been used as nucleophiles with unsaturated oxazolones. Initially, Michael reaction of a trialkyl- or dialkylphosphite gives 617 or 619 that undergo subsequent ring opening to yield a 2-acylamino-3-phosphonyl-618 or 2-acylammo-3-phosphinyl-620 derivative of the corresponding carboxylic acid, respectively (Scheme 7.198). ° ... 

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. 

The reactivity of unsaturated 5(477)-oxazolones can be divided in two main categories according to the reaction site, ring-opening reactions, and reactions of the exocyclic double bond. 

Michael Reaction. 5(47/)-Oxazolones undergo base-catalyzed conjugate addition to activated unsaturated compounds to afford the corresponding C-4 Michael adducts. For example, base-catalyzed addition of a 4-monosubstituted-5(4//)-oxazolone 157 to methyl propiolate yields a mixture of diastereomeric methyl 3-(5-oxo-2-phenyl-2-oxazolin-4-yl)acrylates 158. Hydrolytic ring opening of 158 and subsequent oxidation with lead tetraacetate affords 3-acylacrylates 160... 

In general, the reaction of unsaturated 5(4//)-oxazolones 497 with nitrogen nucleophiles effects ring opening to give the corresponding unsaturated acylamino amides 498 (Scheme 7.158). Depending on the nucleophile, for example, amines, hydrazines, oximes, and so on, the products obtained can be cyclized and this process allows the synthesis of a wide variety of new heterocyclic compounds. 

In contrast, ethyl 3-oxo-4-(triphenylphosphoranylidene)butyrate behaves as a C,0-bis(nucleophile) when reacted with unsaturated 5(4//)-oxazolones 584 with a leaving group at the exocyclic p-carbon. In this case, initial Michael reaction generates 585 that eliminates HX to produce a resonance stabihzed ylide 586. Cyclization of 586 with ring opening leads to the interesting ylide intermediate 587 used for the synthesis of 2//-pyran-2-ones (Scheme 7.185). 

Unsaturated 5(4H)-oxazolones undergo a Friedel-Crafts reaction with aromatic hydrocarbons in the presence of a Lewis acid. In particular, a 2-aryl-4-benzylidene-5(4H)-oxazolone 598 reacts with o- or p-xylene in the presence of aluminum chloride via ring opening and subsequent dearylation to yield 599 as indicated in Scheme 7.191. ... 

Sulfur ylides are among the most interesting carbon nucleophiles and their synthetic importance has been recently reviewed.One especially interesting use of these ylides is their application to the synthesis of cyclopropane derivatives using unsaturated oxazolones. For example, stabilized sulfur yhdes react with unsaturated oxazolones 629 via a Michael reaction to give oxazolone spirocyclopropanes 630 as shown in Scheme 7.202 and Table 7.46 (Fig. 7.57), whereas the less stabilized sulfur ylides give ring-opened products 631 as the major compounds (Scheme 7.202). ... 

The difference is interestingly exemplified in the differing modes of reaction of hydrazoic acid with some alkylidene (and arylidene) oxazolone derivativesThe alkylidene compound 174 behaves as an a, -unsaturated carbonyl compound with the hydrazoic acid adding to the exocyclic double bond. A subsequent ring opening with further addition leads to the formation of the diazide 175 (equation 75). In contrast the exocyclic double bond of the arylidene compound 176 is unreactive, and nucleophilic attack occurs at the... 

Unsaturated azlactones ordinarily do not react readily with hot alcohols. However, if either an acid > or a base is added to the ethanol, the oxazolone ring is opened rapidly with the formation of an a-acyl-aminoacrylic ester. With sodium hydroxide or alkoxide the reaction is complete in three to five minutes at room temperature. > With sodium carbonate as catalyst a short period of refluxing is required. Azlactones also react rajadly with higher alcohols in the presence of the sodium alkoxide. ... 

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