Oxiranes chiral

Oxirane (1) and methyloxirane (3) are miscible with water, ethyloxirane is very soluble in water, while compounds such as cyclopentene oxide and higher oxiranes are essentially insoluble (B-73MI50501) (for a discussion of the solubilities of heterocycles, see (63PMH(l)l77)). Other physical properties of heterocycles, such as dipole moments and electrochemical properties, are discussed in various chapters of pmh. The optical activity of chiral oxiranes has been investigated by ab initio molecular orbital methods (8UA1023). 

The remarkable stereospecificity of TBHP-transition metal epoxidations of allylic alcohols has been exploited by Sharpless group for the synthesis of chiral oxiranes from prochiral allylic alcohols (Scheme 76) (81JA464) and for diastereoselective oxirane synthesis from chiral allylic alcohols (Scheme 77) (81JA6237). It has been suggested that this latter reaction may enable the preparation of chiral compounds of complete enantiomeric purity cf. Scheme 78) ... 

Die Stereochemie der Oxiran-Reduktionen mit Lithiumalanat entspricht dem SN2-Mechanismus. Chirale Oxirane werden unter Walden-Umkehr aufgespalten. So erhalt man z.B. aus r>(+)-2,3-Dimethyl-oxiran mit Lithium-tetradeuterido-aluminat in 86% iger Ausbeute r>(-)-erythro-3-Deutero-butanol-(2)i2. 

Schmid, A., Hofstetter, K., Feiten, H.J., Holhnann, R, Witholt, B. (2001) Integrated Biocatalytic Synthesis on Gram Scale The Highly Enantio Selective Preparation of Chiral Oxiranes with Styrene Monooxygenase. Advanced Synthesis Catalysis, 343(6-7), I il-l il. 

The chiral oxirane derivative 185 (R = 4-BrCgH4CH2) and vinylmagnesium bromide yield the allylic amine 186 allylmagnesium bromide reacts in an analogous fashion192. 

Chiral p-hydroxyethylammonium catalysts decompose under strongly basic conditions with the extrusion of a tertiary amine to produce chiral oxiranes, which contaminate the reaction products and lead to spurious conclusions about the enantioselective nature of the reaction (Chapter 12). 

Epoxidation of alkenes can be effected by potassium persulphate. When the oxidation is conducted in the presence of chiral trifluoroketones, chiral oxiranes (ee 12-22%) are produced [14]. The chirality appears to be achieved via the initial reaction of the persulphate with the ketone to generate chiral dioxiranes, which then interact with the alkenes. 

Powdered KOH (113 mg) is added to the aryl aldehyde (0.6 mmol), the chloromethyl-sulphone (0.5 mmol) and A-(4-trifluoromethyIbenzyl)quininium bromide (28 mg, 0.05 mmol) in PhMe (3 ml) at room temperature and the mixture is stirred for 2 h. Aqueous HCI (l M, 3 ml) is added to quench the reaction and the mixture is extracted with AcOEt (3 x 15 ml). The extracts are washed with brine (10 ml), dried (Na2S04), and evaporated to yield the chiral oxirane. 

Method B The quininium salt (0.05 mmol) and LiOH (47.9 mg) are added to the alkene (1 mmol) in CHClj (3 ml) and aqueous H202 (30%, 1 ml) at -10°C and the mixture is stirred for ca. 5 h at-10C. Aqueous HCI (1M, 3 ml) is added and the mixture is extracted with Et20 (3x15 ml) and washed with brine (20 ml). Evaporation of the dried (Na2S04) organic phase yields the chiral oxirane. ( Optimum ee was obtained using the N-(a-naphthyl) salt.)... 

Method C ( Bu02H in PhMe (80%, 10 ml) is added with stirring at room temperature to the alkene (15 mmol) and W-benzylquininium chloride (0.5 g, 1.1 mmol) in PhMe (10 ml). The mixture is stirred for 5 h, Et20 (25 ml) is added, and the mixture is extracted with H20 (4 x 50 ml). The dried (MgS04) organic phase is evaporated to yield the oxirane. Method D Aqueous NaOCl (115 g, 1.2 ml) is added to the alkene (1 mmol) and chiral catalyst (0.1 mmol) in PhMe (10 ml) at 250 C. The mixture is stirred for 24-48h and H20 (5 ml) is then added. The aqueous phase is separated, extracted with EtOAc (10 ml), and the combined organic solutions are dried (Na2S04) and evaporated to yield the chiral oxirane. 

The catalysed reaction of a,p-unsaturated ketones with dialkylzincs and oxygen leads to the formation of chiral acyloxiranes. The initially formed intermediate complex between the chiral (3-hydroxyamine and the dialkylzine (cf. Scheme 12.9) is oxidized to the peroxyalkylzinc complex prior to the formation of the chiral oxirane (Scheme 12.13) [28]. 

Diazotization of AAs proceeds via the corresponding a-hydroxy acids to oxiranes. From chiral starting material chiral oxiranes are obtained with retention of configuration. This synthetic principle is generally applicable (79T1601 89TL5505). 

By contrast, lithium enolates derived from tertiary amides do react with oxiranes The diastereoselectivity in the reaction of simple amide enolates with terminal oxiranes has been addressed and found to be low (Scheme 45). The chiral bicyclic amide enolate 99 reacts with a good diastereoselectivity with ethylene oxide . The reaction of the chiral amide enolate 100 with the chiral oxiranes 101 and 102 occurs with a good diastereoselectivity (in the matched case ) interestingly, the stereochemical course is opposite to the one observed with alkyl iodides. The same reversal is found in the reaction of the amide enolate 103. By contrast, this reversal in diastereoselectivity compared to alkyl iodides was not found in the reaction of the hthium enolate 104 with the chiral oxiranes 105 and 106 °. It should be noted that a strong matched/mismatched effect occurs for enolates 100 and 103 with chiral oxiranes, and excellent diastereoselec-tivities can be achieved. 

Examples for and have been observed under certain experimental conditions for reactive and/or strained chiral oxiranes which were separated by complexation gas chromatography (Figure 21)133. The first eluted peak was diminished in the separation of racemic 2-methyl-3-phenylo.xirane. In this case two enantioselective processes are mediated by the chiral metal chelate, i.e., chromatographic resolution and kinetic resolution (in favor of the first eluted enantiomer). Since two enantioselective processes are involved, the elution profile will be the same svhen the chirality of the metal chelate is inverted. 

By the extension of the above-mentioned stereoselective asymmetric addition of alkylithiums to other organolithium reagents such as lithium salts of methyl phenyl sulfide, 2-methylthiazoline, trialkylsilylacetylene, N-nitroso-dimethylamine, and acetonitrile, chiral oxiranes (95) U1), thiiranes (96) nl), acetylenic alcohols (98) 112), and amino alcohols (97) U1) were readily obtained. 

The original racemic patents described the use of resolution to give a chiral oxirane, such as 25, as an intermediate or the use of a chiral auxiliary (20) to produce the salmeterol enantiomers. Alkylation of chiral amine 20 with 2-benzyloxy-5-(2-bromo-acetyl)-benzoic acid methyl ester, followed by diastereoselective reduction of the ketone with lithium borohydride furnished intermediate 21 after chromatographic separation of the diasteromers. Removal of the benzyl group and the chiral auxiliary was... 

A three-step protocol (92T10515, 92TL2095) converts chiral diols, efficiently into chiral oxiranes (Scheme 10). 

The conversion of alkenes to oxiranes using ketone catalysts in the presence of a terminal oxidant such as Oxone has proved to be an important advance in the past decade, especially for the formation of chiral oxiranes (see Section 1.03.4.3.3(ii)). The conversion of alkenes to oxiranes has been comprehensively reviewed <20020R219>. The formation of the dioxirane species usually proceeds in situ, whether it be the formation of methyl(trifluoromethyl)-dioxirane in an academic setting <1995JOC3887>, or under conditions amenable to large-scale conversion of aromatic alkenes to oxiranes (oxone, acetone, ethyl acetate, no phase-transfer catalysis) <20020PD405>. 

Epoxide formation using biocatalysis is a useful process for the formation of chiral oxiranes (Scheme 29). The synthesis of enantioenriched epoxides using enzymes has been reviewed <1995BCSF769>. Chloroperoxidase has been examined for the oxidation of 2-methyl-l-alkenes, among other alkenes. The yields in some cases can be low, but the enantioselectivities can be high <1995JA6412, 1997JA443>. This enzyme has been used in a synthesis of... 

As in CHEC-II(1996), emphasis will be placed on epoxides fused to small rings or other systems with unusual structural features. Methods of generation will focus on chiral oxiranes and those methods which allow access to... 

This remains a developing area for the synthesis of chiral oxiranes and has attracted interest from several research groups. As with the use of dioxiranes (above), it is not necessary to form the reactive oxaziridinium salt rather, the epoxidation reaction can be mediated by the corresponding iminium salt and Oxone. 

Finally, mention may be made of those articles in which this method is utilized in the synthesis of optically active oxiranes for example, the simple synthesis of monosubstituted (S)-oxiranes and the asymmetric cyclization of some chlorohydrins catalyzed by optically active cobalt (salen)-type complexes, or in the enantiomeric selection of racemic oxiranes via halohydrins and /3-hydroxy sulfides. A useful three-step synthesis has been worked out from (S)-amino acids to (R)-alkyloxiranes as well as enantiomer resolution for chiral oxiranes by complexation gas chromatography. ... 

The enantioselective total synthesis of triterpenes of the jS-amyrin series has been described by Corey and co-workers who utilized a MeAlCl2-catalyzed tricarbocyclization of a chiral oxirane <93JA8873>, see also <91TL7005>. 

This classical example of oxirane synthesis involves treatment of a halohydrin with base <84CHEC-1(7)115,85CHE1,85MI103-01). Kolb and Sharpless introduced a three-step protocol <92X10515,92TL2095) whereby chiral diols, available by Sharpless asymmetric dihydroxylation <92JOC2768>, are efficiently converted into chiral oxiranes (Scheme 55). 

A. Toshimitsu, H. Abe, C. Hirosawa, S. Tanimoto, Preparation of chiral aziridines from chiral oxiranes with retention of configuration, /. Chem. Soc. Chem. Commun. (1992) 284. 

A. Schmid, K. Hofstetter, H. J. Feiten, F. Hollmann, B. Witholt, Integrated biocatalytic synthesis on gram scale The highly enantioselective preparation of chiral oxiranes with styrene monooxygenase, Adv. Synth. Catal. 343 (2001) 732. 

Halo-substituted acetophenones such as m-bromo- [74] or p-chloroacetophe-none [46] were reduced with borane in high enantioselectivity in the presence of oxazaborolidines 4b and 47, respectively. Other important halogen-containing ketones are chloromethyl or bromomethyl ketones. Oxazaborolidine reduction of co-chloro- or co-bromoacetophenone gives enantio-enriched halohydrins that can be converted into chiral oxiranes [20]. Martens found that the sulfur-containing oxazaborolidine catalysts 60 show high enantioselectivity in this kind of reduction [44, 86, 87]. Enantiopure halohydrins were obtained as shown in Scheme 8. 

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