Oxazole 2,5-endoperoxides

In principle, reaction of an oxazole, e.g., 15 with 2 could yield triamides 693 and/or 696 via two reasonable pathways (Scheme 1.194). In the first case, path A, [4 + 2] cycloaddition of 02 to 15 would yield an oxazole-2,5-endoperoxide 691. Rearrangement of 691 to an imino-anhydride 692 by a Bayer-Villiger-like reaction and subsequent O-acyl to A/-acyl transfer would produce triamide 693. Alternatively, [2 + 2] cycloaddition of 02 to 15 would produce the dioxetane 694, cleavage of which would then yield a second imino-anhydride 695, which could also undergo an O-acyl to /V-acyl transfer reaction to produce triamide 696. 

Additional evidence to support an oxazole 2,5-endoperoxide intermediate was obtained by isolation of the spirolactone 700 (Scheme 1.194). The authors proposed that 700 was generated from 699 by intramolecular capture of an intermediate carbocation with the suitably positioned carboxylic acid side chain. They also concluded that addition of 2 to oxazoles was a concerted reaction based on a lack of solvent or substituent effects. 

Gollnick and Koegler also conducted detailed mechanistic studies of the [4 + 2] cycloaddition of O2 with oxazoles. The authors characterized the first examples of disubstituted oxazole 2,5-endoperoxides 702 (Scheme 1.195). These endoperoxides were particularly interesting since the presence of an olefinic proton permitted structure assignment based on low-temperature (—50 C) H and NMR data. The authors were able to mle out 694 and 703-705 as possible intermediates in this reaction, and they unequivocally identified the intermediates as the oxazole 2,5-endoperoxides 702. 

The endoperoxides (49) of oxazoles also undergo clean rearrangements following the path outlined in Scheme 6 <88TL1007>. The initial product is a dioxazole (50) identified at low temperature by NMR spectroscopy <90JCS(P1)1011>. Subsequent products are the imino anhydride (51) followed by... 

The only examples of 1,2,4-trioxolanes containing A-linked substituents arise from photooxygenation of oxazoles. The endoperoxides thus produced are bicyclic, with a 1,2,4-trioxolane ring bridged by an imine moiety and are unstable at ambient temperature. They have been characterized at low temperature and thermal rearrangement is described in Section 4.16.5.1.1. 

Fused ring oxazoles lead, in apolar solvents, to products which derive from cleavage at the 2-3 and 4-5 positions of the endoperoxides to cyano-anhydrides 81 followed by hydrolysis or CO loss. This sequence has been efficiently used to prepare oo-cyano carboxylic acids 82 (Sch. 47) [78],... 

Isoxazoles, 1,2,5-oxadiazoles and 1,3,4-oxadiazoles are apparently inert under dye-sensitized photo-oxygenation [74a], while a thiotriamide has been found in the photo-oxygenation of arylthiazole presumably via the undetected endoperoxide in a fashion similar to oxazoles [67,80]. 

Wasserman and Floyd ° first demonstrated the dye-sensitized photooxidation of oxazoles to prepare triamides 255 in 1966 (Fig. 3.75). This reaction has since become a valuable synthetic tool. Several reports have now appeared that establish the mechanism of this transformation to proceed through an initial [4-P 2]-cycloaddition to provide an unstable 2,5-endoperoxide, 252. Oxygen-18 studies were consistent with the formation of 252 and excluded the formation of an... 

The heterocyclic 1,3-dienes such as pyrroles, thiazoles, ° and oxazoles are also reactive and afford endoperoxides on photooxygenation. Most of these ozonide-type cycloadducts have neither been isolated nor detected but have been postulated as plausible reaction intermediates. 

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