Oxirane openings

Alkyl groups under nonacidic conditions sterically deflect nucleophiles from C, but under acidic conditions this steric effect is to some extent offset by an electronic one the protonated oxirane opens by transition states (Scheme 40) which are even more 5Nl-like than the borderline Sn2 one of the unprotonated oxirane. Thus electronic factors favor cleavage at the more substituted carbon, which can better support a partial positive charge the steric factor is still operative, however, and even under acidic conditions the major product usually results from Cp attack. 

The commonest of these for oxirane opening are amines and azide ion [amide ions promote isomerization to allylic alcohols (Section 5.05.3.2.2)]. Reaction with azide can be used in a sequence for converting oxiranes into aziridines (Scheme 49) and this has been employed in the synthesis of the heteroannulenes (57) and (58) (80CB3127, 79AG(E)962). 

Oxirane opening by functionalized ethenylaluminum (81JA1851) and ethenylcopper (79JCS(Pl)2954) reagents has found applications in natural products synthesis. 

In contrast to the relative chemical stability of mono-epoxides, diol epoxides of fatty acids (10.52), which are formed from di-epoxides by EH, are subject to a different fate. In such metabolites, intramolecular nucleophilic substitution may occur, such that oxirane opening is accompanied by formation of a tetrahydrofuran ring [134], Such reactions of intramolecular nucleophilic substitution are discussed in detail in Sect. 11.9. In the case of diol epoxides of fatty acids, the resulting tetrahydrofuran-diols (10.53) are part of a much larger ensemble of oxygenated metabolites of fatty acids, the potential cytotoxicities of which are being evaluated [135]. 

Fig. 10.23. Simplified reactivity and metabolism of tetrachloroethylene oxide (10.94) and 1,3-dichloropropene oxide (10.97). In both cases, the conditions dictate the relative contributions of heterolytic oxirane opening with Cl migration and oxirane hydration followed by loss of...

A related amination/rearrangement/cyclization tandem sequence had been introduced by Cossy [49]. Starting from cyclic epoxyketones 224 the reaction with propargylamines 225 caused an oxirane-opening condensation process to generate the enaminoketones 226. Upon heating in toluene to reflux, aza-Claisen rearrangement delivered the intermediate allenyl imines 227, which... 

Similarly, the epoxide (72), on reaction with BH3/UBH4, acetic acid or BC13 gave the tetrahydrothiophene derivatives (74a-c), presumably via the intermediate (73), unlike the analogous cyclohexyl and N-alkylpiperidyl compounds, in which the oxirane opened to give only the expected alcohols (equation 21) (75CPB2701). 

In a development involving racemic products, nonactivated /V-benzyl (3-lactam 117, is shown to be opened selectively with methyllithium to yield, after intramolecular oxirane opening, the methyl ketone 118, Scheme 39. This compound is transformed through several steps into the nicotinic acetylcholine receptor agonist anatoxin-a [106]. 

Stereoselective preparation and Cope rearrangement of 2-CF3-substituted r-2,3-bis(alkenyl)oxiranes opens a facile approach to diverse 2-trifluoromethyl-4,5-dihydrooxepines. Subsequent reduction or oxidation of the latter provide 2-CF3-substituted oxepanes or oxepines, respectively <2004CL438>. 

C-l Reactivity of 2,3-epoxy alcohols via oxirane opening with metal halides applications and synthesis of naturally occurring 2,3-octanediol,... 

M. S. J. Blaney, W. M. Oxirane-opening reactions of some 6,19-oxygenated 4a,18-epoxy-neo-clerodanes isolated from teucrium. Biogenesis and antifeedant activity of their derivatives. Tetrahedron 1994, 50, 5451-5468. 

Protection of 194 as a p-methoxybenzylether and subsequent epoxydation led to the trans-epoxide 195, which was transformed into the unsaturated aldehyde 196 by a three-reaction sequence, including regioselective oxirane opening with a 1,3-dithiane anion, hydrolysis of the dithioacetal formed, and dehydration. Chlorite promoted aldehyde oxidation, methyl ester formation, and removal of the hydroxyl protections delivered methyl (+)-shikimate 197 in a remarkable 12% yield from 193. 

From epoxides. A very efficient access to tetrahydrofuran derivatives has been developed based on ring opening of oxiranes with selenolates. For instance, preparation of 2,4-disubstituted tetrahydrofurans from epoxides is shown in Eq. (3) [ 11 ]. Opening of the epoxide 19 with diphenyldiselenide/NaBH4 followed by prenylation gives the radical precursor 20 in excellent yield. Cyclization furnishes the tetrahydrofuran 21 in almost quantitative yield but with a modest stereocontrol. The oxirane opening approach described here competes with the electrophilic alkoxyselenenylation reported below (Sect. 2.1.2). 

The stereochemistry of oxirane opening has been studied in the reactions of cis-127 and trans- 128 1-phenyl-1,2-epoxypropanes with dialkylmagnesium. 128 reacts on the carbon atom adjacent to the phenyl group and exclusively threo-alcohol is formed. In the case of 127, the reaction also takes place on the other carbon atom and an alcohol mixture is obtained.The importance of steric factors is demonstrated in studies with mircenemagnesium. ... 

Selective oxirane opening takes place in the presence of a ketone group (Eq. 256). ... 

FIGURE 9.7 a Na2S and b Intramolecular nucleophilic oxirane opening by thiolate. 

More remote substituents may also participate in epoxide opening/rearrangement. Christol and coworkers examined several S,(6)-substituted-2,3-norbomene ejco-oxides under acidic conditions, and found that certain 5-endo substituents played a part in oxirane opening. For example, oxa rings were formed in reactions of substrates bearing 5-entfo-methoxycarbonyl or -hydroxymethyl groups. A novel 1,4-migration of chloride was also detected (equation 28). ... 

Diethyl 2,3-epoxy-4-oxoalkylphosphonates can be converted on reaction with thioureas and thioamides into diethyl 2-hydroxy-2-(5-thiazolyl)ethylphosphonates or into 2-(5-thiaz-olyl)vinylphosphonates (Scheme 4.49)."" Cleavage of both systems into phosphorus-free thiazoles can be readily achieved with CsF in DMF. Reaction of diethyl 2,3-epoxy-4-oxoalkylphosphonates with 2-mercaptobenzimidazole yields oc-substituted enones arising from regioselective oxirane opening and subsequent dehydration (Scheme 4.49). °° These derivatives exist, mainly or exclusively, as cyclic tautomers. The cyclization step depends on the reaction conditions. °°... 

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