Epoxides and Related Substrates

Asymmetric ring-opening of saturated epoxides by organocuprates has been studied but only low enantioselectivities ( 15% ee) have so far been obtained [49 SO]. Muller et al. for example, have reported that the reaction between cydohexene oxide and MeMgBr, catalyzed by 10% of a chiral Schiffbase copper complex, gave trafxs-2-methylcydohexanol in 50% yield and with 10% ee [50]. 

Sdieme S.26. Kinetic resolution of cyclic vinyl oxiranes 44. 

The process was Sn2 -selective in the presence of catalytic amounts of ligands (S)-32 or (SjRjR)-43 and Cu(OTf)2. This is another example of ligand-accelerated catalysis vtithout the ligand the reaction was much slower and proceeded vtith low regioselectivity. 

When 0.5 equivalents of dialkylzinc were used, ees of more than 90% were obtained, vtith reasonable isolated yidds of up to 38% [52] of the Sn 2 -substituted 

8 Copper-Mediated Enan oselective SabstittAtion Reactions 

A number of structurally very different copper complexes were employed as catalysts. The copper complex of binaphthol-derived phosphoramidite 32 and the Schiff base complex 53 (derived from salicylaldehyde and phenylglycine) gave promising results in a screening reaction between 52 and MeMgBr, and 53 was chosen as the candidate for optimization. The effect of solvent (THF or Et20), 

Hie same autliors also studied tlie alkylation of alkynyl epoxides for fornialion of optically active a-aUenic alcohols under kinetic resolution ctmdilions fSdieme 8.29) [54]. 

Copper-catalyzed desymmetrlzabon of N-tosylazirldine 52 witli Grlgnard reagents 

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The kinetic resolution of aziridines has also been reported. Alper showed that the car-bonylation of N-ferf-butyl- and N-adamantyl-2-arylaziridines in the presence of catalytic amounts of the combination of [Rh(COD)Cl]j and enantiopure menthol produced the corresponding N-alkyl-3-phenylazetidin-2-ones in up to 99.5% optical yield, although the isolated yields were modest. Consistent with the cobalt-catalyzed carbonylation of epoxides and related substrates, inversion of configuration occurs at the site of carbonyl insertion. 

Dimesityldioxirane, a crystalline derivative, has been isolated by Sander and colleagues and subjected to X-ray analysis. The microwave and X-ray data both suggest that dioxiranes have an atypically long 0—0 bond in excess of 1.5 A. Those factors that determine the stability of dioxiranes are not yet completely understood but what is known today will be addressed in this review. A series of achiral, and more recently chiral oxygen atom transfer reagents, have been adapted to very selective applications in the preparation of complex epoxides and related products of oxidation. A detailed history and survey of the rather remarkable evolution of dioxirane chemistry and their numerous synthetic applications is presented in Chapter 14 of this volume by Adam and Cong-Gui Zhao. Our objective in this part of the review is to first provide a detailed theoretical description of the electronic nature of dioxiranes and then to describe the nuances of the mechanism of oxygen atom transfer to a variety of nucleophilic substrates. 

RESOLUTION OF RACEMIC ALCOHOLS AND RELATED SUBSTRATES. Under certain conditions, enantiomers react at sufficiently different rates and they provide a chemical means to resolve racemates (Scheme 31) (64). The Sharpless epoxidation efficiently resolves allylic alcohols that have flex-le structures (64, 65). Homogeneous hydrogenation with (/ )- or (S)-... 

The CUps-O epoxide 33-41 and related substrates are currently the only available selective fluorogenic substrates for EH. On the other hand various indirect assays have been reported to detect either the unreacted epoxide [46] or the carbonyl product resulting from periodate cleavage of the 1,2-diol product [26,47, 48], These assays are suitable for fluorescence or colorimetric assays for the hydrolysis of any epoxide of interest... 

Roberts has shown that the asymmetric epoxidation of chalcone can be catalysed by polyamino acid derivatives under non-aqueous conditions [13]. This improved reaction involves the use of a urea-hydrogen peroxide complex in THF, in the presence of an organic base (DBU) and immobilized poly-(L)-leucine. Under these conditions, the reaction of chalcone derivatives and related substrates provided the corresponding epoxides in 70-99% yield and 83-95% ee within 30 min. Several substrates with enolisable enones have also been epoxidized successfully [14]. 

Mioskowski et al. have demonstrated a route to spirocyclopropanes. As an example, treatment of epoxide 100 with n-BuLi in pentane stereoselectively gave tricyclic alcohol 101, albeit in only 47% yield (Scheme 5.21) [29]. With a related substrate, epoxide 102 stereoselectively gave dicydopropane 103 on treatment with PhLi uniquely, the product was isolable after column chromatography in 74% yield [35]. As was also seen with attempts to perform C-H insertion reactions in a non-transannular sense, one should note that steps were taken to minimize the formation of olefin products, either by the use of a base with low nudeophilicity (LTM P) and/or by slow addition of the base to a dilute solution (10-3 m in the case of 102) of the epoxide. 

The information obtained with the model substrate dibenzol ,d cyclo-heptene 10,11-oxide has helped us understand why related tricyclic drugs yield modest or very low proportions of dihydrodiols, despite formation of the 10,11-oxides. For example, both the epoxide and the dihydrodiol were characterized in the urine of rats given protriptyline (10.129, X = MeNH-CH2CH2CH2CH), but cyclobenzaprine (10.129, X = Me2NCH2CH2CH=C) did not yield the dihydrodiol despite the epoxide and other oxygenated metabolites being formed in vivo and in vitro [194],... 

Closely related substrates such as )5-methyl styrene epoxide and dihydro-naphthalene epoxide and derived trans diols were not substrates for this particular microorganism. 

Nature often uses two pathways to produce oxygenated molecules. One is oxidative fictionalization of substrates through enzymatic hydration, monohydroxylation, dihydroxylation or epoxidation. Alternatively, oxygenated compounds can be generated by C—C formation catalyzed by aldolase, transketolase, oxynitrilase and related enzymes, where chiral centers are created simultaneously without an overall change in oxidation states [78]. 

A group of related bacterial enzymes hydroxylate alkanes,507 toluene,508 phenol,509 and other substrates.5093 Eukaryotic fatty acid desaturases (Fig. 16-20B) belong to the same family.508 Some bacteria use cytochrome P450 or other oxygenase to add an oxygen atom to an alkene to form an epoxide. For example, propylene... 

Partial ergot alkaloid substrates of 5 and related, conformationally fixed styrenes 6-8 have been found to undergo electrophilic additions (epoxidation, HOBr addition and... 

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