Opening of oxides

A facile method for the stereospecific labeling of carbon atoms adjacent to an oxygenated position is the reductive opening of oxides. The stereospecificity of this reaction is due to virtually exclusive diaxial opening of steroidal oxides when treated with lithium aluminum hydride or deuteride. The resulting /ra/w-diaxial labeled alcohols are of high stereochemical and isotopic purity, with the latter property depending almost solely on the quality of the metal deuteride used. (For the preparation of m-labeled alcohols, see section V-D.) 

Lithium aluminum deuteride reduction of the 2a,3a-oxide function has been carried out with a number of different 5a-steroids (227). ° The isotopic purity of the resulting 2 -d,-3a-ols (228) is usually 96-100%. By mild oxidation, under Jones conditions, these alcohols can be converted into stereospecifically labeled monodeuterio ketones (229) ° of high isotopic purity. (For an alternate preparation of certain a-monodeuterio ketones, see section VI-B.) 

Other successful applications of this reaction are the preparation of 

6j5-di-7a-liydroxy and 16j5-di-17a-hydroxy steroids from the corresponding 6a,la- and 16a,17a-oxido derivatives. 

The course of the ring opening in epoxides derived from various exocyclic methylene compounds by treatment with lithium aluminum deuteride has been studied in the norbornane series.  

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The alcoholysis of a-epoxides gives hydroxy ethers in a trans opening of the ring. An example is the treatment of cyclohexene oxide with methanol under reflux in the presence of a small quantity of sulfuric acid, trans-2-methoxycyclohexanol being formed in 82% yield. The mechanism and stereochemistry of the opening of oxide rings have been reviewed. ... 

Cyclic compounds capable of undergoing ring opening (alkylene oxides, lactones, lactams, anhydrides, etc.). 

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

Tertiary alcohols are usually degraded unselectively by strong oxidants. Anhydrous chromium trioxide leads to oxidative ring opening of tertiary cycloalkanols (L.F. Fieser, 1948). 

We saw an example of nucleophilic ring opening of epoxides in Section 15 4 where the reaction of Grignard reagents with ethylene oxide was described as a synthetic route to primary alcohols... 

As we ve just seen nucleophilic ring opening of ethylene oxide yields 2 substituted derivatives of ethanol Those reactions involved nucleophilic attack on the carbon of the ring under neutral or basic conditions Other nucleophilic ring openings of epoxides like wise give 2 substituted derivatives of ethanol but either involve an acid as a reactant or occur under conditions of acid catalysis... 

FIGURE 16 6 The mecha nism for the acid catalyzed nucleophilic ring opening of ethylene oxide by water... 

The reactions are highly exothermic. Under Uquid-phase conditions at about 200°C, the overall heat of reaction is —83.7 to —104.6 kJ/mol (—20 to —25 kcal/mol) ethylene oxide reacting (324). The opening of the oxide ring is considered to occur by an ionic mechanism with a nucleophilic attack on one of the epoxide carbon atoms (325). Both acidic and basic catalysts accelerate the reactions, as does elevated temperature. The reaction kinetics and product distribution have been studied by a number of workers (326,327). 

With W-substituted quaternary derivatives in the presence of oxidizing agents, ring opening is avoided and the classical Dekker oxidation of the pseudo-base occurs to give (45) (62JCS1671). 

The nitrosation of pyrroles and indoles is not a simple process. The 3-nitroso derivatives (84) obtained from indoles exist largely in oximino forms (85) (80IJC(B)767). Nitrosation of pyrrole or alkylpyrroles may result in ring opening or oxidation of the ring and removal of the alkyl groups. This is illustrated by the formation of the maleimide (86) from 2,3,4 -trime thylpyrrole. 

Oxidation to an azolone is an expected reaction for a pseudo base, but little appears to be known of such reactions. Most commonly, pseudo bases suffer ring fission. Estimated rates of ring-opening of (169) are in the ratio 10 10" 1 for X = O, S and NMe, respectively (79AHC(25)1). 

Treatment of benzo derivatives with oxidizing agents leads to less predictable results. Thus, substituted 2,1-benzisoxazoles with nitrous acid or with CrOs/AcOH generated a variety of ring-opened products of higher oxidation state, the ratio of which depended on the amount of oxidant. These reactions are illustrated in Scheme 30. 

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