2-oxazoline substituted epoxides

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>. 

Epoxides also participate in the Ritter reaction with nitriles. An investigation of the ring opening of several alkyl-substituted glycidic esters and amides 181 showed that this transformation occurs with inversion and is completely regiospecific. ° Esters appeared to be somewhat more reactive than amides. However, phenyl-substituted glycidic esters and amides 184 are almost totally nonstereoselective. In addition, the oxazolines 186 are isolated in low yield due to the propensity of intermediate 185 to generate an aldehyde byproduct 187 (Scheme 8.53). 

Oxazolines.1 Reaction of 1,1-disubstituted epoxides with nitriles and SiF4 (1 equiv.) provides fluorohydrins, which oti further exposure to SiF4 are converted into 2-oxazolines, in which the nitrogen is attached to the substituted carbon. In the example cited, the yield is increased to 81% from reactions conducted at 80°. 

Tridentate salen ligands (10) derived from 1 have given excellent results in the enantiocontrol of the hetero Diels-Alder addition reaction of dienes with aldehydes (eq 7) and in the asymmetric additions of TMS-azide to mc5o-epoxide and trimethylsilyl cyanide to benzaldehyde (up to 85% ee). Phosphino-oxazolines derived from 1 have been employed for the asymmetric control of palladium-catalyzed allylic substitution reactions products of 70-90% ee were obtained. Photolysis of crystalline adducts of enantiomerically pure 1 with prochiral alcohols results in asymmetric inductions of up to 79% in a rare example of a solid-state enantioselective reaction. ... 

There has been a fuller account given of the formation of the 2,2 -anhydro-system 18 ftom the 2, 3 -ene by treatment with N-bromoacetamide (see Vol. 26, p. 227). Treatment of 18 with NaOH in acetone formed the D-Zyro-epoxide 19. When the xylose-derived nucleoside 20 was treated with diphenyl carbonate and NaHCOs, the 2,2 -anhydronucleoside 21 was obtained, and it was proposed that the mechanism of this process proceeded through the 3 ,5 -cyclic carbonate and the 2, 3 -ribo-epoxide as intermediates. Treatment of 21 with pyridinium bromide followed by hydrogenolysis gave thymidine. The oxazoline 22 can be used as a precursor of various 5-substituted 2,2 -anhydrouridine derivatives, as in the case shown in Scheme 2. The... 

The ambident nature of cyanotrimethylsilane can lead to the formation of nitriles or isocyanides, depending on the nature of the catalyst. For example, cyanotrimethylsilane reactions with epoxides and oxetanes catalyzed by soft Lewis acids give rise to 2-(trimethylsiloxy) isocyanides arising by attack on the more substituted carbon (eqs 15 and 16).Milder reaction conditions and better yields of isocyanides can be realized when the reaction of cyanotrimethylsilane with oxiranes is carried out in the presence of Pd(CN)2, SnCL, or MesGa (eq 17). Isocyanides are useful precursors for the synthesis of /3-amino alcohols and oxazolines. 

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