Oxazolines 4,5-Dihydrooxazoles

The overall pathway for the conversion of the unsaturated azido ether 281 to 2,5-dihydrooxazoles 282 involves first formation of the dipolar cycloaddition product 287, which thermolyzes to oxazoline 282 or is converted by silica gel to oxazolinoaziridine 288. While thermolysis or acid-catalyzed decomposition of triazolines to a mixture of imine and aziridine is well-documented [71,73], this chemoselective decomposition, depending on whether thermolysis or exposure to silica gel is used, is unprecedented. It is postulated that acidic surface sites on silica catalyze the triazoline decomposition via an intermediate resembling 289, which prefers to close to an aziridine 288. On the other hand, thermolysis of 287 may proceed via 290 (or the corresponding diradical) in which hydrogen migration is favored over ring closure. 

Cyclization of. V-alkeny lam ides to 2-oxazolines was achieved in very mild conditions with fert-butyl hypoiodite <06OL3335>. The 5-exo-dig gold(I)-catalyzed cyclization of propargylic trichloroacetimidates 129 proceeded with remarkably efficiency under very mild conditions to give 4-methylene-4,5-dihydrooxazoles 130 in good yields. The mildness of the protocol was clearly responsible for the lack of isomerization of the final products to the corresponding, thermodynamically more stable, oxazoles <06OL3537>. 

While monitoring the conversion via 1H NMR spectroscopy, an intermediate 5-methylene-4,5-dihydrooxazole could be observed and accumulated up to 95% and this is the first direct and catalytic preparative access to such alkylidene oxazolines. 

In this chapter, oxazole and its derivatives are named and numbered as in Chemical Abstracts. Thus compound (6) is called 4,5-dihydrooxazole rather than 2-oxazoline or A2-oxazoline, (7) is 2,5-dihydrooxazole, the betaines (3) are named anhydro-5-hydroxy-oxazolium hydroxides and not oxazolium 5-oxides or oxazolium 5-olates, and the oxo derivatives (4) and (5) are 5(4//)-oxazolone and 5(2//)-oxazolone, respectively, the position of the extra hydrogen atom being indicated in parentheses. The fully saturated compound (8) is oxazolidine its oxo derivatives are named oxazolidinones and oxazolidinediones, e.g. compound (9) is 2-oxazolidinone and (10) is 4,5-oxazolidinedione. A formula such as (11) is not meant to imply that all the substituents are methyl groups it represents a general oxazolidine derivative and is used in place of the cumbersome expression (12 R-R = H, alkyl or aryl). 

Other 2,3-Dihydrooxazoles and -thiazoles from a-Amino Acids. Table 1 shows oxazolines and thiazolines also prepared... 

Oxazoles 1, benzoxazoles 2, oxazolium salts 3, and oxazole A -oxides 4 are fully conjugated compounds (Figure 1). In addition, the two mesoionic structures l,3-oxazolium-5-olates 5 and (l,3-oxazolium-4-olates) 6, commonly known as miinchnones and isomiinchnones, respectively, are also considered to be conjugated rings. There are five systems of hydroxyl-substituted oxazoles and they exist in their oxo forms the 2(3H)-, 2(5H)-, 4(5//)-, 5(2//)-, 5(4//)-oxazolones 7-11. Three forms of dihydrooxazoles are known 2,3-, 2,5-, and 4,5-dihydrooxazoles respectively 12-14. The fully saturated ring is called oxazoline 15. The monooxo derivatives are 2-oxazolidinone 16,4-oxazolidinone 17, and 5-oxazolidinone 18. The three variants of oxazolidinediones are 19-21 and the fully oxidized oxazolidi-netrione is 22. 

Dihydrooxazoles continue to occupy an important place in organic synthesis and medicinal chemistry as they have found use as versatile synthetic intermediates, protecting groups/pro-drugs for carboxylic acids, and chiral auxiliaries in asymmetric synthesis. There are several protocols in the literature for the transformations of functional groups such as acids, esters, nitriles, hydroxyl amides, aldehydes, and alkenes to 2-oxazolines. Newer additions to these methods feature greater ease of synthesis and milder conditions. 

Dihydrooxazoles 275 can be made by the condensation of aryl nitriles with amino alcohols catalyzed by Bi(iii) salts <2005SL2747> or acidic clay <1998TL459> in good yields (Bi salts - 70-92% kaolinitic clay -56-96%) (Equation 16). The use of Bi salts is only applicable to the formation of 2-aryloxazolines while the latter method works well for both aromatic as well as aliphatic substrates. The conversion of carboxylic esters to 2-oxazolines 276 in good (44-82%) yields with lanthanide chloride as catalyst <1997TL7019> has also been described (Equation 17). 

As in CHEC-I <84CHEC-I(6)177>, the naming and numbering of oxazole and its derivatives follow the convention of Chemical Abstracts. The fully conjugated compounds are called oxazoles (1), benzoxazoles (2), oxazolium salts (3), and oxazole A -oxides (4). Hydroxy-substituted oxazoles exist in the oxo form, and there are five representatives the 2QH)-, 2(SH)-, 4(5//)-, 5(2//)-, and 5(4//)-oxazolones, (5)-(9) respectively. There are two mesoionic structures, the anhydro-4-hydroxy-oxazolium hydroxides (10) and the 5-hydroxy analogues (11), the latter of which are also referred to as the munchnones. Compound (12) is named 4,5-dihydrooxazole instead of A -oxazoline or 2-oxazoline, which is commonly used in the general literature. The other dihydrooxazoles include the less common 2,3- and 2,5-dihydrooxazoles, (13) and (14), respectively. The fully saturated compound... 

I 4,5-Dihydrooxazole was previously known as A -oxazoline or 2-oxazoline. It follows from mi-crowave spectra that the ring is planar. 

This synthetic application of 4,5-dihydrooxazoles is known as the Meyers oxazoline method [76]. 

A new simple synthetic route to 2,5-dihydrooxazoles 71 by cycloaddition of allyl azido ethers 70 via triazoUnes was shown by Hassner et al. [37]. Earlier, they demonstrated that cr-azido ethers can be easily prepared from aldehydes using an alcohol, hydrazoic acid and titanium tetracliloride as well as the fact that thermolysis of azido ethers in the absence of a double bond forms imi-dates [35,36]. Using the above mentioned facts, the allyl azido ethers 70 were synthesized in good yields employing an aldehyde, an allyl alcohol and HN3 in a 1 3 9 ratio in presence of a Ti catalyst (Scheme 12). Allyl azido ethers 70, on thermolysis in benzene, proved to be ideal substrates for the formation of 2,5-dihydrooxazoles 71 in 66-90% yield. To show that oxazolines are formed via triazolines and not via an independent nitrene pathway, thermolysis of 70 was followed by NMR in hexadeuteriobenzene at 70 °C. 

Oxazoline Derivatives. Oxazolines are of great interest because of their ability to undergo cationic ring-opening poljunerization. In this connection, the functionalized monomers A(-[4-(4, 5 -dihydrooxazol-2-yl)phenyl]acryl amide (5a), A -[4-(4, 5 -dihydrooxazol-2-yl)phenyl]-2-methacryl amide (5b), N- 10-[4-(4, 5-dihydrooxazol-2-yl)phenylcarbamoyl]decyl -2-acryl amide (6a),... 

Oxazoline see 4,5-dihydrooxazole 2-Oxazolin-5-one 184 Oxepan-2-one 532 Oxepin 529 Oxetane 45... 

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