Cyclization 4,5-dihydrooxazole

Asymmetric synthesis of tricyclic nitro ergoline synthon (up to 70% ee) is accomplished by intramolecular cyclization of nitro compound Pd(0)-catalyzed complexes with classical C2 symmetry diphosphanes.94 Palladium complexes of 4,5-dihydrooxazoles are better chiral ligands to promote asymmetric allylic alkylation than classical catalysts. For example, allylic substitution with nitromethane gives enantioselectivity exceeding 99% ee (Eq. 5.62).95 Phosphi-noxazolines can induce very high enatioselectivity in other transition metal-catalyzed reactions.96 Diastereo- and enantioselective allylation of substituted nitroalkanes has also been reported.9513... 

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>. 

As already shown for dihydrothiazole-containing cyclic peptides (Section 6.8.5.2.2.2), basically two different synthetic routes are used for the introduction of dihydrooxazoles into cyclic peptides. In the first one, 2-(aminoalkyl)dihydrooxazole-4-carboxylic acids and related derivatives are synthesized,t554 571,572 589 590 then incorporated directly into the linear precursors, which are finally cyclized by standard protocols.1541.554.567.569.5711 Again the main disadvantage to this synthetic approach is the facile racemization of the dihydrooxazole syn-thon. Therefore, the preferred method is the production of the oxazolidine ring in the preassembled cyclic peptide. For this purpose various methods have been proposed. 

Rhodiumcatalyzed decomposition of 10a in the presence of benzaldehyde and methyl cyanoformate does not afford the dihydrooxazole derived fi om carbonyl ylide 21, but rather the interestingly functionalized 1,3-oxazole [19]. This product is likely to arise from cyclization of the nitrile ylide intermediate 26 [20]. 

Dihydrooxazoles and 5,6-Dihydro-4//-1,3-oxazines by Cyclization of O-Allylic and O-Homoallylic Imidates... 

Dihydrooxazoles were also obtained by cyclization of imidates induced by mercury salts. Thus, treatment of an allylic alcohol with dimethylcyanamide in the presence of sodium hydride gave the corresponding imidate 9 in 90% yield. Subsequent cyclization, performed in tetrahy-drofuran with mercury(II) trifluoroacetate followed by cleavage with sodium borohydride, gave a single enantiomer of the 4,5-dihydrooxazole 10 in 80% yield157. 

The formation of 10 proceeded with total regio- and stereoselectivity, since cyclization occurs only from the /(-face, with the imidate nitrogen attacking the more substituted C-3 position. When the corresponding trichloroacetimidate was treated under the same conditions, a mixture of both the 4,5-dihydrooxazole and a 2-oxazolidinone were produced, the latter most probably arises from the hydrolysis of the 4,5-dihydrooxazole. 

Benzenetellurinyl trifluoroacetate converts olefins in the presence of acetonitrile, propionit-rile, or benzonitrile, in a reaction catalyzed by boron trifluoride-diethyl etherate to 2-acylamino-1-ethyl phenyl tellurium oxides. The mixture was then heated at 75° for 3 h to elfect elimination of the phenyltelluro group and cyclization to the dihydrooxazole. ... 

The selenoxide produced by oxidation of Y-(2-phenylselenylethyl)benzamide with MCPBA undergoes cyclization to furnish 4,5-dihydrooxazoles in high yield <92TL4017>. An optically active amide bearing a 2-pyridylseleno group on the p carbon (186) is cyclized without racemization (Equation (25)). 

Dihydrooxazoles are also accessible by phenylselenyl bromide <9lJOC3425> or phenylselenyl sulfate <93J0C1349> induced cyclization of Y-allylamides. Oxidation of the 5-phenylselenylraethyl... 

Optically active bis(4,5-dihydrooxazoles), which are effective ligands for asymmetric synthesis (Section 3.04.12.5), have been prepared by zinc chloride-catalyzed coupling of amino alcohols and dinitriles <91CB1173> and by sodium hydroxide induced cyclization of bis(A-(2-chloroethyl)amides) <91JA728>. 

Acetyl azides like 94 can be cyclized to dihydrooxazoles 95 in high yield (Fig. 35). Furthermore, the protocol can be extended to six-membered rings as shown in Fig. 36 for the synthesis of pipecolic acid 100 from azido-aldehyde 96. 

---