2-Oxazolines reaction with amines

In these reactions, the formation of imidazoline and oxazoline rings corresponds to the reagent orientation previously observed for ynamines (84ZOR1648) and alkenylynamines (83ZOR926), as well as in their reactions with mononucleophiles such as amines (79ZOR1824 81ZOR1807) and alcohols (80ZOR1141). 

In two patents, Bloom 572 has described how 2-, 3-, and 4-benzo[6]-thienylisocyanate may be converted by reaction with jS-haloethyl-amines into the corresponding A-(benzo[6]thienyl)-A -/3-haloethyl-ureas (204) which readily cyclize to 2-(benzo[6]thienylamino)-oxazolines (205) on being boiled in aqueous solution. 

Toward a complete synthesis of trehazolin (2), 2,3,4,6-tetra-O-benzyl-1 -deoxy-z-D-glucopyranosyl isothiocyanate (7)52 was brought into reaction with the amines 5 and 374 in the presence of triethylamine to afford the x-D-glucopyranosyl thiourea derivatives 375 or 376, respectively (Scheme 46).38 Subsequent treatment with 2-chloro-3-ethylbenzoxazolium tetrafluoroborate and triethylamine afforded the corresponding amino oxazoline derivatives 377 and 378. Finally, hydrogenation over Pd(OH)2 on carbon afforded trehazolin (2). 

Amine 249 was treated with 2% HCl-MeOH followed by reaction with Et3N and isothiocyanate 7 to give 414. Treatment of 414 with 2-chloro-3-ethylbenzoxazolium tetrafluoroborate gave the protected oxazoline 415 (90%), which upon hydrogenolysis with Pd(OH)2 on carbon gave the trehalostatin diepimer 416 in 46% yield (Scheme 55).106,107... 

So far the reactivity of epoxides has involved their use as an electrophile. However, oxtranyl anions can serve as functionalized nucleophiles in their own right. Thus, the sulfonyl substituted epoxide 107 can be deprotonated with -butyllithium to provide a stabilized anion which engages in facile Sn2 reaction with triflate 108 <03JOC9050>. Other examples of such stabilized epoxide anions include those derived from oxazolinyloxiranes (e.g., 110), which react with nitrones to provide the spirotricyclic heterocycles of type 112, Hydrolysis provides the epoxy amino acids 113, in which the carboxylic acid moiety was provided by the oxazoline nucleus and the amine functionality was derived from the nitrone <03OL2723>. A recent report has demonstrated that oxiranyl anions can also be stabilized by the amide functionality <03H(59)137>. 

A two-step synthesis of 1,4-disubstituted imidazoles (8) from TOSMIC (1) plus an aldehyde, followed by reaction with ammonia or a primary amine, proceeds via a 4-tosyloxazoline (11). The reaction sequence could be classified as 1,2 and 1,5 bond formation, 1,5 bond formation, or transformation of another heterocycle. There are, however, analogies to the aldimine reactions, and so the process is detailed at this stage. Certainly the synthesis is carried out in two steps often with isolation of the oxazoline (see also Chapter 6). Heating (11) with a saturated solution of methanolic ammonia gives a 4-substituted imidazole with methanolic methylamine a 1,4-disubstituted product is isolated as a single regioisomer (Scheme 4.2.4). Some of the oxazolines cannot be isolated as they are unstable oils which have to be heated immediately with the amino compound [12]. Related is the synthesis of 2-carbamoyl-4-(2 -deoxy- 0-D-ribofuranosyl)imidazole [13]. 

Highlights of iome reactions of phosgene with amines, imines. oxazolines... 

By using Cu complexes of chiral spiro bis(oxazoline) ligand S, S,S)-23a as catalysts, the enantioselective catalytic insertion of a-diazoesters into N—H bond of aromatic amines was realized in high yields and high enantioselectivities (Scheme 43) [25b, 108]. The chiral spiro Cu catalysts have unique binuclear structures, as showing in Figure 6, which may address the excellent performance of the Cu-(S, S,S)-23a catalyst for this challenging reaction. With the Cu-catalyzed asymmetric N—H... 

As imido esters, dihydro-1,3-oxazines of type 14 display reactivity similar to 2-oxazolines (see p 135). The a-C-H bonds of the 2-alkyl group are CH-acidic. They are metalated by reaction with butyllithium and then undergo C-C forming reactions with electrophiles such as haloalkanes, oxiranes or carbonyl compounds. The dihydro-1,3-oxazines 16, which are obtained from 15 by a-metalation and alkylation, undergo reduction with NaBH4 forming 17. Acid hydrolysis cleaves the cyclic aminal function of 17 yielding aldehydes 18 ... 

Glycosylimino-oxazolines such as the a-D-mannosylimino-derivative 33 have been prepared as further analogues of trehazoline, and their glycosidase inhibitory properties determined. Reaction of the glucofurano-isoxazole 34 with amines is known to cause displacement of the thiobenzyl substituent, but it has now been found that unsaturated derivatives such as 35 can be the products formed under forcing conditions (Scheme 6). ... 

Scott et al. compared the development of the phase morphology in non-reactive and reactive polymer blends based on the reaction of maleic anhydride (MA) with amine and oxazoline (OX), respectively. The increase in the mixing torque and decrease in the average particle size were less pronoimced and delayed in time in the case of the MA/OX reactive pair compared to the MA/NH2 one, consistently with the lower reactivity of the former pair [46]. 

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