Oxazolinones unsaturated

Although imidazolinones are usually resistant to hydrolysis, oxazolinone rings are often easily opened. In acid-catalyzed reactions of this type, water converts azlactones (234) into a-acylamino-a,(3-unsaturated acids (235) (77AHC(2i)l75). 1,3,4-Oxadiazolinones are readily opened by hot water to give hydrazine carboxylic acids which undergo decarboxylation. 

Cyclization of an allyl A-acyl-1 -phenylglycinate (398) with triphenylphosphine, hexa-chloroethane and triethylamine affords a 2-allyl-3-oxazolin-4-one (400) (81AG(E)395, 77AG(E)394). Reductive cleavage of the oxazolinone with chromium(II) acetate and aqueous hypophosphorous acid furnishes a j3,y-unsaturated ketone (Scheme 88). 

Recently, Kunz reported that dialkylaluminum chlorides add in a 1,4-mode to N-(a,f3-unsaturated acyl)oxazolidones (9 Scheme 3),12 while high enantioselectivity is obtained with the chiral N-(a, 3-un-saturated acyl)oxazolinone (11). Typically, higher dialkylaluminum halides (R = ethyl, isobutyl) do not... 

Heteroaromatic compounds are also suitable nucleophiles in the Michael additions to enals catalysed by prolinol silyl ethers. Hayashi and coworkers demonstrated that oxazolinones can add effectively to enals (Scheme S.lSa)." Indole also added effectively to a,p-unsaturated aldehydes (Scheme 8.13b). Also, enantioselective Michael addition of simple 3(2H)-furanones to a,(3-unsaturated aldehydes has been described (Scheme 8.13c). ... 

Unsaturated a-Amino-acids. - Oxazolinones (515), readily derived from N-benzoylglycine and ethyl chloroformate, condense smoothly with aromatic aldehydes, N-phenylaldimines, or cyclohexanone to... 

The chemistry of unsaturated oxazolinones has been the subject of several detailed reviews (25, 95, 106, 107, 126, 127, 322, 398) so that attention here will be focussed primarily on those more recent studies not dealt with in the literature cited. Unsaturated oxazolinones for the synthesis of dehydropeptides can be obtained by several different routes ... 

P) In 1926, Bergmann and Stern described an alternative route to unsaturated oxazolinones (40). Treatment of a-haloacylamino acids with acetic anhydride, usually in the presence of bases such as pyridine or sodium acetate, affords A -or A -oxazolinones (14) and (15), depending on the stabilization of the double bond system by the substituents R [cf. (396, 398). The 2-methyl-4-alkylidene (aralkylidene) oxazolinones obtained by Bergmann et al. (40, 114) and by Greenstein and Price (319) from the chloroacetyl derivatives of Phe, Tyr, Leu, Norleu, Val and Aba, from which the corresponding acetyldehydroamino acids could be obtained by hydrolysis, were most probably A -oxazolinones. In contrast, the product obtained from a-bromopropionyl alanine, which can very readily be cleaved to pyruvic acid, is probably an example of a A -oxazolinone. 

Y) Oxazolinone formation from P-hydroxyamino acids leads to unsaturated oxazolinones owing to simultaneous elimination of the P-substituent. Erlenmeyer 117) described the formation of 2-methyl-4-benzylidene-oxazolinone by the reaction of phenylserine with acetic anhydride. Carter et al 92, 93, 94) obtained 2-phenyl-4-ethylidene-oxazolin-5-one from N-benzoylthreonine, N-benzoylallothreonine, and their 0-methyl, 0-acetyl and 0-benzoyl derivatives by treatment with benzoylchloride in pyridine. Trifluoroacetic anhydride converts threonine into 4-ethylidene-2-trifluoromethyl-2-oxazolin-5-one 20). 

S) Several attempts have been made, especially in recent years, to oxidize saturated to unsaturated oxazolinones. Oxazolinone formation activates the a-carbon atom of the corresponding amino acid, so that it can, for example, by easily brominated 100, 315, 417). Morin and Gordon 267) attempted the selective oxidation of the C-terminal amino acid of a peptide chain by first converting it into an oxazolinone. Treatment of the oxazolinones obtained from N-benzoyl- or N-carbo-benzoxydipeptides with Pb(OAc)4 or Hg(OAc)2 resulted however in... 

Following publication by Weygand and coworkers 432, 433) of their studies of the bromination of 2-trifluoroacetyl-A -oxazolinones at the p-carbon atom of the corresponding amino acid, Breitholle and Stammer (68, 69) described the elimination of HBr from these bromo-derivatives (17) to yield unsaturated A -oxazolinones (18). The latter yielded N-trifluoroacetyldehydroamino acid anilides (19) or peptides on treatment with aniline or amino acid esters respectively. Muller and Steglich (270) used this method independently for the synthesis of N-trifluoroacetyl-dehydrodipeptides (20) containing C-terminal alanine. 

---