Preparation of Oxiranes

Bromomethyl)-lithium in the Preparation of Oxiranes Ethyl 2-Methyloxirane-2-propanoate. 

Crocker, M., Herold, R.H.M. (Shell Oil Company, USA) (1998) Preparation of oxirane compounds with titanasilsesquioxane catalysts. US PCT 97/783965. 

Some examples of the preparation of oxiranes, thiiranes and aziridines by the reaction of diazo compounds with trifiuoromethyl-substituted carbonyl161 - 164 and thiocarbonyl compounds,165 imines,166167 and oximes168 arc known. However, as noted in Section 2.1.1.6.2.5.1., carbenes are not always the reactive species. Thus, the reaction can consist of a 1,3-di polar cycloaddition, followed by decomposition of the resulting pyrazoline. 

In both the synthetic organic laboratory and industry, the first and foremost procedure for the preparation of oxiranes is the direct oxidation of alkenes. Significant new results have been achieved in the development of methods of oxidizing alkenes in the liquid phase. The major aim is the attainment of an oxidation reaction under the mildest possible experimental conditions, which allows an increase in the selectivity of oxirane formation and permits the selective oxidation of more sensitive compounds. Since the various methods of preparing oxiranes were reviewed quite recently, the individual oxidation procedures will be mainly illustrated here with some more recent examples. Surveys concentrating on stereo-controlled epoxidations and assymmetric synthetic methods have been published. "... 

Chromic acid oxidation of olefins can rarely be used for the preparation of oxiranes because they occur as intermediates that rapidly undergo further transformation. From an investigation of the mechanism of oxidation of triaryl-substituted olefins, it was concluded that a carbonium ion or cyclic chromate ester is a possible intermediate. Selective epoxidation of compounds containing conjugated double bonds is attainable by means of chromic-acid oxidation (Eq. 48) 535 Exclusively cis product was obtained from a highly substituted octalin with Na2Cr04, KMn04, or ozone (Eq. 49). ... 

Preparation of Oxiranes from 1,2-Difunctional Compounds by 1,3-Elimination... 

Halohydrin has been produced in the presence of a free radical initiator for the preparation of oxirane fluorinated in the side-chain (Eq. 61). ... 

Preparation of Oxiranes from Carbonyl Compounds by Formation of Carbon-Carbon Bonds... 

A new catalytic redox procedure has been devised for the preparation of oxiranes from ketones or ketoalcohols with Cu alkoxides (e.g., Cu(OCH3)Cl pyridine) (Eq. 99). ... 

Dimethylthioformamide (DMTF) (234) reacts with oxiranes (235) in the presence of a catalytic amount of trifluoroacetic acid under mild conditions to form the corresponding thiiranes in good yield as shown in Scheme 79 and Table 37 <86S779>. A possible reaction mechanism is postulated based on the mechanism observed in the preparation of oxiranes with thiocyanate or thiourea <66CRV297>. Intermediate (236) is generated by the nucleophilic attack of the sulfur atom of (234) on the carbon atom of (235) followed by ring closure reaction of the hydroxy oxygen atom with the iminium carbon atom. Subsequent elimination of dimethylformamide affords thiirane (237). 

Two studies on the use of chiral phase-transfer catalysts in the preparation of oxirans have been reported. " ... 

Besides direct hydrolysis, heterometaHic oxoalkoxides may be produced by ester elimination from a mixture of a metal alkoxide and the acetate of another metal. In addition to their use in the preparation of ceramic materials, bimetallic oxoalkoxides having the general formula (RO) MOM OM(OR) where M is Ti or Al, is a bivalent metal (such as Mn, Co, Ni, and Zn), is 3 or 4, and R is Pr or Bu, are being evaluated as catalysts for polymerization of heterocychc monomers, such as lactones, oxiranes, and epoxides. An excellent review of metal oxoalkoxides has been pubUshed (571). 

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) ... 

Many functional groups are stable to alkaline hydrogen peroxide. Acetate esters are usually hydrolyzed under the reaction conditions although methods have been developed to prevent hydrolysis.For the preparation of the 4,5-oxiranes of desoxycorticosterone, hydrocortisone, and cortisone, the alkali-sensitive ketol side chains must be protected with a base-resistant group, e.g., the tetrahydropyranyl ether or the ethylene ketal derivative. Sodium carbonate has been used successfully as a base with unprotected ketol side chains, but it should be noted that some ketols are sensitive to sodium carbonate in the absence of hydrogen peroxide. The spiroketal side chain of the sapogenins is stable to the basic reaction conditions. 

Due to the abundance of epoxides, they are ideal precursors for the preparation of P-amino alcohols. In one case, ring-opening of 2-methyl-oxirane (18) with methylamine resulted in l-methylamino-propan-2-ol (19), which was transformed to 1,2-dimethyl-aziridine (20) in 30-35% yield using the Wenker protocol. Interestingly, l-amino-3-buten-2-ol sulfate ester (23) was prepared from l-amino-3-buten-2-ol (22, a product of ammonia ring-opening of vinyl epoxide 21) and chlorosulfonic acid. Treatment of sulfate ester 23 with NaOH then led to aziridine 24. ... 

The living nature of ethylene oxide polymerization was anticipated by Flory 3) who conceived its potential for preparation of polymers of uniform size. Unfortunately, this reaction was performed in those days in the presence of alcohols needed for solubilization of the initiators, and their presence led to proton-transfer that deprives this process of its living character. These shortcomings of oxirane polymerization were eliminated later when new soluble initiating systems were discovered. For example, a catalytic system developed by Inoue 4), allowed him to produce truly living poly-oxiranes of narrow molecular weight distribution and to prepare di- and tri-block polymers composed of uniform polyoxirane blocks (e.g. of polyethylene oxide and polypropylene oxide). 

The living polymerization of lactones, oxiranes, and thiiranes became also possible by improved preparation of the Al—Zn oxyalkoxides. These catalysts were first studied by Tsuruta 6) and by Vanderberg 7), and later by Teyssie 8 b). 

Sulfonic peracids (66) have also been applied recently to the preparation of acid sensitive oxiranes and for the epoxidation of allylic and homoallylic alcohols, as well as relatively unreactive a, p - unsaturated ketones. These reagents, prepared in situ from the corresponding sulfonyl imidazolides 65, promote the same sense of diastereoselectivity as the conventional peracids, but often to a higher degree. In particular, the epoxidation of certain A -3-ketosteroids (e.g., 67) with sulfonic peracids 66 resulted in the formation of oxirane products (e.g., 68) in remarkably high diastereomeric excess. This increased selectivity is most likely the result of the considerable steric requirements about the sulfur atom, which enhances non-bonded interactions believed to be operative in the diastereoselection mechanism <96TET2957>. 

Oxidation of cyclic phosphonoformaldehyde dithioacetal, using the Modena protocol, yields the trans disulfoxide 121 in excellent enantiomeric excess. Then 121, via HWE olefination and oxidation of the double bond has been used for the diastereoselective preparation of spirocyclic his-sulfinyl oxiranes (new versatile intermediates in asymmetric synthesis) [79] (Scheme 37). 

It may be concluded that the conversion of functionalized oxiranes into the corresponding aziridines by an azide ring opening followed by a Staudinger ring closure with triphenylphosphine constitutes a general method for the preparation of aziridines with high enantiopurity. 

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 rate of hydrozirconation of a terminal olefin is much faster than the reduction of the oxirane ring. This chemoselectivity was used in the preparation of various cycloalkylmethanols by hydrozirconation of alkenyloxiranes (Scheme 8-28) [217]. 

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