L- oxazoles

There has been no report on this kind of compound in the literature for the period concerned. The perhydro derivatives were, on the contrary, well-studied for several years and applied in a variety of routes for the total synthesis of natural products or to produce optically active derivatives, mainly following the Meyers protocol <1984JA1146>. Only two examples of dihydropyrrolo[2,l- ]oxazoles are available and one example of a tetrahydro derivative is described. 

The studies of the reactivity of saturated pyrrolo[2,l- )oxazoles are in general associated with the reactivity of Meyers chiral bicyclic lactams and their applications in asymmetric synthesis. 

Cleavage of 5-(3-phenyl-hexahydro-pyrrolo[2,l- ]oxazol-5-yl)-pent-3-en-2-one 195, when conducted in methanol with HC1 gas, produced compounds 196 and 197 in an 80/20 ratio, or after treatment with sulfuric acid in methanol at 60 °C afforded 198 as a single isomer (Scheme 26). Compound 198 was used for the total synthesis of the potent neurotoxic (-F)-ferruginine <1997JOC6704>. 

Aromatic pyrrolo[2,l- ]oxazoles are unknown compounds. Dihydro derivatives 228 and 229 have been obtained from the thermal rearrangement of dihydrooxazole 226 through intermediate 227 (Scheme 32) <2003EJ01438>. 

When l-[diazo(methoxycarbonyl)acetyl]-2-oxopyrrolidine derivative 231 was treated with Rh2(pfm)4 (pfm = per-fluorobutyro amidate) in the presence of W-phenylmaleimide, none of the desired dipolar cycloadduct was formed but instead the acidic proton at C-3 in the isomiinchnone intermediate 232 was transferred, and the fused oxazoli-dinone 3-oxo-2,3,5,6-tetrahydropyrrolo[2,l- ]oxazole-2,7-dicarboxylic acid dimethyl ester 233 was isolated in 77% yield (Scheme 33) <1997JOC6842>. 

When the diazoimides 253 are subjected to Rh2(OAc)4 at 80 °C in presence of an alkyl alcohol, pcrhydropyrrolo[2,1 -b -oxazol-4-ones 254 were isolated in good yields as a diastereomeric mixture. If the alcohol is replaced by terminal alkyl diols, the corresponding bis(2,3-fused perhydropyrrolo[2,l- ]oxazol-4-one) systems 255 were obtained (Scheme 37) <2003CC440>. 

Lewis acid SnCLj-assisted reaction between the l,3-thiazole-5-thione 434 and /ra r-2,3-dimethyloxirane led to the m 4,5-dimethyl-l,3-oxathiolane 435 The same Lewis acid enabled a second addition of /ra/ -2,3-dimcthyloxirane onto the C—N bond of the 1,3-thiazole ting of 434, leading to the formation of the tetrahydro-2//-thiazolo[2,3- ]-oxazole adduct 436 (Equation 200) <2000HCA3163>. Condensation of 2,4-dinitroimidazole, 8-bromotheophylline, and 8-bromoadenine with substituted methyloxiranes involved sequential A -alkylation-r/wo-substitution and furnished a series of 2,3-dihydro-imidazo[2,l- ]oxazole derivatives 437, 438, and 439 (Equations 201-203) <2000CCC1126, 2000EJ03489, 2005TL3561, 2004JHC51>. 

Related Reagents. (5)-l-Amino-2-methoxymethylpyrroli-dine fra/w-2,5-Bis(methoxymethyl)pyrrolidine 10,2-Cam-phorsultam 10-Dicyclohexylsulfonamidoisobomeol a-Me-thyltoluene-2,a-sultam (35,cw)-Tetrahydro-3-isopropyl-7a-methylpyiTolol[2,l-l>]oxazol-5(6/f)- one. 

When ethylene oxide is used to alkylate 2,4-dinitroimidazole, 60% of the N-alkylated product is formed, but 25% of the product is a bicyclic nitroimidazo[2,l- >]oxazole (223) which must be formed as a result of intramolecular nucleophilic displacement of the 2-nitro group (Scheme 122) (79JHC1499). 

E Acids and anhydrides F Esters G Lactones H Phenols I Furans and pyrans J Thiophenes K Pyrroles L Oxazoles M Thiazoles N Pyridines O Pyrazines... 

Substituted derivatives of 7-phenyl-l-(oxazol-2-yl)heptane-l-one (113) have been shown to inhibit the enzyme fatty acid amide hydrolase with inhibition constants as shown Table 6.17. Predict the fCj value of the 5-trifluoromethyl derivative. 

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