Unsaturated, enantioselective epoxidation

Enantioselective epoxidation of a.p-unsaturated ketones by diethylzinc and oxygen... 

Asymmetric epoxidation of a,jS-unsaturated ketones represents an efficient method for the preparation of optically active a,jS-epoxy ketonesJ Recently, a new and very efficient catalytic system for enantioselective epoxidation of ( )-a,jS-enones to the corresponding trans-epoxy ketones has been developed based on a BlNOL-zinc complexJ Very high yields and excellent diastereo- and enantioselectivities are achieved at room temperature using cumene hydroperoxide (CMHP) as the terminal oxidant and performing the reaction in diethyl ether. A combination of enantio-merically pure BINOL and diethylzinc readily affords the active catalyst in situ (Figure 6.13). ... 

Masakatsu Shibasaki of the University of Tokyo reports (J. Am. Chem. Soc. 2004,126, 7559) that use of a BINOL-derived catalyst with cumyl hydroperoxide enables the enantioselective epoxidation of unsaturated N-acyl pyrroles such as 7. The pyrroles 7, prepared from the precursor aldehydes such as 5 with the reagent 6, can be used directly, without further purification. 

The Julia-Colonna epoxidation uses poly-L-leucine and hydrogen peroxide to effect enantioselective epoxidation of chalconc derivatives such as 12. In a pair of back-to-back papers (Tetrahedron Lett. 2004,45, 5065 and 5069), H.-Christian Militzer of Bayer Healthcare AG, Wuppertal, reports a detailed optimization of this procedure. In the following paper (Tetrahedron Lett. 2004,45,5073), Stanley Roberts of the University of Liverpool reports the extension of this procedure to unsaturated sulfones such as 14. 

The C = C bond in the hydroxy allylic system of a fluoroalkanol can be selectively epoxidized without affecting the hydroxy group. Enantioselective epoxidation of racemic unsaturated fluoro alcohols by using the chiral Sharpless reagent can be exploited for the kinetic resolution of enantiomers. The recovered stereoisomer (e.g., 1) has 14-98% enantiomeric excess.165... 

The catalytic asymmetric epoxidation of electron-deficient olefins, particularly a,P-unsaturated ketones, has been the subject of numerous investigations, and as a result a number of useful methodologies have been elaborated [44], Among these, the method utilizing chiral phase-transfer catalysis occupies a unique position in terms of its practical advantages. Moreover, it also allows the highly enantioselective epoxidation of trans-a,P-unsaturated ketones, particularly chalcone. 

The ratio of jy -epoxide (shown above) to anti-epoxide is 10—25 1 with TYZORTPT catalysis, whereas vanadylacetylacetonate is less selective and / -chloroperoxybenzoic acid gives the reverse 1 25 ratio. It is supposed that TYZOR TPT esterifies the free hydroxyl, then coordinates with the peroxide to favor syn-epoxidation (135). This procedure is related to that for enantioselective epoxidation of other allylic alcohols in 9—95% enantiomeric excess (135). Titanates trigger peroxide-initiated curing of unsaturated polyesters to give products of superior color, compared to conventional cobalt-initiated... 

Similar conditions are also effective for the direct enantioselective epoxidation of a,p-unsaturated carbonyls, as exemplified by the conversion of chalcone (30) to the corresponding ft,/ -epoxide in 97% yield and 84% ee using the 4-iodophenyl cinchonine derivative 32 <02T1623>. Alternatively, the novel polyethylene glycol-supported oligo(L-leucine) catalyst... 

The bulk of oxidations with tert-butyl hydroperoxide consists of epoxidations of alkenes in the presence of transition metals [147, 215, 216, 217, 218]. In this way, a,p-unsaturated aldehydes [219] and ketones [220] are selectively oxidized to epoxides without the involvement of the carbonyl function. Other applications of tert-butyl hydroperoxide such as the oxidation of lactams to imides [225], of tertiary amines to amine oxides [226, 227], of phosphites to phosphates [228], and of sulfides to sulfoxides [224] are rare. In the presence of a chiral compound, enantioselective epoxidations of alcohols are successfully accomplished with moderate to high enantiomeric excesses [221, 222, 223]. 

C. Bassin, A. Gusso, F. Pinna, G. Strukul, Platinum-catalyzed oxidations with hydrogen peroxide The (enantioselective) epoxidation of a,p-unsaturated ketones, Organometallics 14 (1995) 1161. 

D. Jayaprakash, Y. Kobayashi, S. Watanabe, T. Aral, H. Sasai, Enantioselective epoxidation of a,( -unsaturated ketones using polymer-supported lanthanoid-BlNOL complexes. Tetrahedron Asymmetry 14 (2003) 1587. 

A one-pot epoxidation/azide-opening sequence has been developed <05JA2147>. A samarium-BINOL-PhjAsO complex is used as a catalyst for enantioselective epoxidations of a,p-unsaturated amides. Upon addition of TMSN, a new samarium azide complex is generated which regioselectively opens the epoxide to form 120. This method has also been extended to thiols and cyanide. 

Several examples are known of the enantioselective conversion of alkenes into epoxides with the use of polymer-supported oxidation catalysts. This can be traced to the pioneering work by Julia and Colonna in 1980. They demonstrated that highly enantioselective epoxidations of chalcones and related a, 3-unsaturated ketones can be achieved with the use of insoluble poly(a-amino acids) (116, Scheme 10.20) as catalysts [298-301]. The so-called Julia-Colonna epoxidation has been the object of several excellent reviews [302-306]. The terminal oxidant is H202 in aq. NaOH. With lipophilic amino acids as the components, such as (SJ-valine or (SJ-leucine, enantioselectivities as high as 96-97% ee were obtained. The enan-tioselectivity depends of several factors, including the side-chain of the amino acid, the nature of the end groups and the degree of polymerization. Thus, for instance,... 

Some homopolymeric amino acids have also found applications as catalysts. Thus, polyol-alanine-Ar-butylamide was successfully used as catalyst for the enantioselective epoxidation of x,/j-unsaturated ketones by hydrogen peroxide (Section D.4.5.2.). The polymer formed from 30 alanine molecules has been found most effective. 

Because of this catalyst degradation, organometallic catalysts are currently the best synthetic reagents for enantioselective epoxidation of olefins. Chiral Mn(III)-salen complexes yield up to 99% ee for cw-disubstituted, tri- and tetra-substituted alkenes [62], but the best results require less desirable oxidants - iodosyl benzene or hypochlorite. Other catalysts accept a more limited substrate range the Sharpless-Katsuki titanium-tartrate ester [65] for allylic alcohols and the JuUa-Colonna epoxidation for a,P-unsaturated ketones [66]. 

Finally, it has to be pointed out that the enantioselective epoxidation of a,p-unsaturated compounds with peroxides can also be considered to happen via a... 

Based on enantioselective epoxidation and subsequent ring opening and closing, the so-called Achmatowicz reaction was developed. This is an organocatalytic one-pot cascade for the annulation of a,(J-unsaturated aldehydes, hydrogen peroxide, p-carbonyl compounds and NBS, which furnish optically active 3-pyrones. Other chiral heterocycles were also assembled by organocatalytic cascade reactions using diaiylprolinol silyl ethers as catalysts. ... 

In 2011 Demizu und Kurihara published stapled and linear helical l-Lcu-based peptides that catalyse enantioselective epoxidation of chalcones with yields up 99% and enantioselectivities up to 99%/ The nucleophilic reaction was carried out with 5 mol% peptide, urea-hydrogen peroxide as oxidant and DBU as base. The most active peptide, which was an efficient catalyst in epoxidation of several a,p-unsaturated ketones, was found to be the stapled heptapeptide containing L-homoserine in the third and seventh positions with a linker in between. 

On the other hand, an enantioselective epoxidation of a,p-unsaturated ketones was developed by Zhu et al. by using easily aceessible and recoverable fluorous a,a-diaryl-L-prolinol as an organocatalyst and tert-butyl hydro-genperoxide (TBHP) as an oxidant. As shown in Scheme 7.5, the corresponding epoxides have been obtained for a number of substrates with moderate to good enantioselectivities of up to 84% ee. 

The Zhao group recently disclosed an enantioselective epoxidation of a,P-unsaturated ketones promoted by primary-secondary diamine catalyst 13c the corresponding epoxides were obtained with excellent enantioselectivities (Scheme 3.19) [55],... 

Besides the success obtained in the epoxidation of enones by either phase transfer catalysts or polyamino acid derivatives, there was not any example of the related reaction with aldehydes 13. Recently, chiral amine 22 was deployed as a soluble catalyst for the enantioselective epoxidation of a, 3-unsaturated aldehydes 13 to give the expected epoxide 55 (Scheme 4.9). 

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