Stereochemistry and mechanism

It was pointed out earlier that the low nucleophilicity of fluoride ion and its low concentration in HF solutions can create circumstances not commonly observed with the other halogen acids. Under such conditions rearrangement reactions either of a concerted nature or via a true carbonium ion may compete with nucleophilic attack by fluoride ion. To favor the latter the addition of oxygen bases, e.g., tetrahydrofuran, to the medium in the proper concentration can provide the required increase in fluoride ion concentration without harmful reduction in the acidity of the medium. 

Epoxide Opening with Hydrogen Fluoride in Chloroform-Ethanoi 

2 -Dihydroxy-9p, -oxidopregn-4-ene-3,2Q-dione 21-Acetate (5). To a solution of anhydrous potassium acetate (158 g) in absolute alcohol (1.6 liters), which has been heated just below reflux temperature is added a solution of 9a-broraocortisol acetate (4, 232 g) in dioxane (745 ml). The mixture is brought to reflux within 3 min and the reaction allowed to proceed for a total of 40 min. After cooling in an ice bath, ice water (4 liters) is added with stirring, upon which crystallization ensues rapidly. The resulting first crop of crystals amounts to 118 g and an additional 30 g is obtained by two successive concentrations of the mother liquors total yield of (5) acetate, 77%. Analytically pure material is obtained by recrystallization from acetone mp 209-211° [ajp 21° 243 m/i (e 15,500). 

Epoxide Opening with 70% Aqueous Hydrogen Fiuoride  

160 ml of 70% aqueous hydrogen fluoride contained in a polyethylene flask chilled to —30° is added, with stirring, a total of 64 g of 17a,21-dihydroxy-16)9-methyl-9j5,l l/5-oxidopregna-l,4-diene-3,20-dione in small amounts while maintaining the temperature below —20°. The reaction mixture is stirred for 4 hr and poured into a solution of 560 g of potassium carbonate in 640 ml of water. The resulting precipitate is isolated by filtration, washed to neutrality with water, and dried. Crystallization from ethyl acetate gives 55 g of the fluorohydrin mp 240-243°. The analytical 

Substituents on the carbonyl compound can also influence the stereo-outcome of the HWE reaction. For example, carbonyl compounds that possess oxygenated groups at the a- or jg-position generally favor the B-alkene [30, 31], although some exceptions have been observed [32]. 

The synthesis of tetrasubstituted alkenes using the HWE reaction generally proceeds with moderate selectivity [33, 34]. 

Factors that favor the E-alkene Factors that favor the Z-alkene 

Bulky R groups on the phosphonate e.g. (R0)2P(0)-CH(-)-R Bulky R groups adjacent to the carbanion e.g. (R0)2P(0)-CH(—)-R Use of a-fluoro phosphonates Use of bis(2,2,2-trifluoroethyl) phosphonates (Still-Gennari modification) Use of cyclic phosphonates such as 8 Use of (diarylphosphono)acetates (Ando method)/ excess Na+ ions 

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Studies by Levisalles and Tkatchenko on the mechanism and stereochemistry of the steroidal benzilic rearrangement have demonstrated that the configuration of the product obtained in about 85 % yield from 5a-cholestane-3,4-dione (27) is as shown (28). When redistilled ethylene glycol mono-... 

Rearrangements have been included in which sulfones participate not only as reactants but also as products. Reactions have been classified according to mechanism, but although the main emphasis has been on mechanism and stereochemistry, special attention to synthetic applications has also been given, wherever appropriate. Obviously, due to space limitations as well as the vast amount of work available, only selected and representative results of general importance, as judged by the concern of the reviewer, are presented below. Thus, the exclusion of a particular piece of work in no way passes judgement on its scientific value. 

Rearrangements have been included in which sulfoxides participate not only as reactants but also as products. Reactions have been classified according to mechanism, but although the main emphasis has been on mechanism and stereochemistry, special attention to synthetic applications has also been given wherever appropriate. 

Monoalkylthallium(III) compounds can be prepared easily and rapidly by treatment of olefins with thallium(III) salts, i.e., oxythallation (66). In marked contrast to the analogous oxymercuration reaction (66), however, where treatment of olefins with mercury(II) salts results in formation of stable organomercurials, the monoalkylthallium(III) derivatives obtained from oxythallation are in the vast majority of cases spontaneously unstable, and cannot be isolated under the reaction conditions employed. Oxythallation adducts have been isolated on a number of occasions (61, 71,104,128), but the predominant reaction pathway which has been observed in oxythallation reactions is initial formation of an alkylthallium(III) derivative and subsequent rapid decomposition of this intermediate to give products derived by oxidation of the organic substrate and simultaneous reduction of the thallium from thallium(III) to thallium(I). The ease and rapidity with which these reactions occur have stimulated interest not only in the preparation and properties of monoalkylthallium(III) derivatives, but in the mechanism and stereochemistry of oxythallation, and in the development of specific synthetic organic transformations based on oxidation of unsaturated systems by thallium(III) salts. 

Trantirek L, K Hynkova, Y Nagata, A Murzin, A Ansorgova, V Sklenar, J Damborsky (2001) Reaction mechanism and stereochemistry of y-hexachlorocyclohexane dehydrochlorinase LinA. J Biol Chem 276 7734-7740. 

The mechanism and stereochemistry of the orthoester Claisen rearrangement is analogous to the Cope rearrangement. The reaction is stereospecific with respect to the double bond present in the initial allylic alcohol. In acyclic molecules, the stereochemistry of the product can usually be predicted on the basis of a chairlike TS.233 When steric effects or ring geometry preclude a chairlike structure, the reaction can proceed through a boatlike TS.234... 

Monocyclic Phosphoranes. - Further studies on the mechanism and stereochemistry of the Wittig reaction have been conducted by a combination of 1H, 13C and 3 P n.m.r.2k 25. The results show that at -18°C both ois and trans diastereomeric oxaphosphetans (e.g. 17 and 18) may be observed and their decomposition to alkenes monitored by n.m.r. Evidence was presented to suggest that during this process oxaphosphetan equilibration involving the siphoning of (17) into (18) occurred in competition with alkene formation. 

Several classes of reactions have now been distinguished and the results are summarized in Table 1 39>, where BR stands for biradical and C stand for concerted. The table illustrates the fact that substituents must be considered in tandem, and that biradical mechanisms are more common for these reactions than concerted reactions. The table is not recommended as a device for predicting mechanism and stereochemistry. Instead, a careful interaction diagram using experimental ionization... 

Hannon and Traylor158 used a specifically labelled organotin hydride, l/iiw-3-deutero-2-trimethylstannylbutane, to determine the mechanism and stereochemistry of the hydride abstraction from an organostannane by a carbocation (equation 101). 

The reaction itself is rather attractive and useful as a synthetic tool, because of its practical simplicity. Indeed, 1,5-dicarbonyl compounds can be readily prepared from olefin and 1,3-dicarbonyl compound in a one-pot reaction. Subsequent aldolization of the resulting 1,5-dicarbonyl compounds would furnish cyclohexenones. The reaction mechanism and stereochemistry of the de Mayo reaction has been comprehensively reviewed7), and the basic strategy of which has also been developed and extended. The following examples would demonstrate some applications and variations of the de Mayo reaction. 

The formation of halogenosulfonium salts is considered to be the first step in the -halogenation of sulfoxides. The mechanism and stereochemistry of a-halogenation of sulfoxides are discussed in detail by Montanari in his recent review paper (9). 

Armstrong, R.N., Enzyme-catalyzed detoxication reactions mechanisms and stereochemistry, CRC Crit. Rev. Biochem., 22 39-88 (1987). 

Pd-CH5CH5C(0)Me. The insertion of CO in the latter Pd-alkyl bond has provided original information on the mechanism and stereochemistry of alternating copolymer blocks incorporating a polar alkene (Scheme 7.26) [25]. 

The boron-oxygen mesomeric effect described in the previous section explains the lower reactivity of allylic boronates towards carbonyl compounds compared to that of allylic boranes. The use of Lewis acids, however, allows boronate derivatives, including hindered ones, to react at temperatures comparable to the analogous boranes. As described above (see section Mechanism and Stereochemistry ), the most reactive allylic boronates are those with the most electrophilic boron centers.The nucleophilicity of the y-position of an allylic boron reagent (the position that forms the new C-C bond with the aldehyde) is also important to the reactivity of the reagent. For example, allylic boronates with... 

Biosynthesis and Metabolism.—Pathways and Reactions. Two reviews of carotenoid biosynthesis discuss, respectively, the early steps and the later reactions." The former paper deals with the mechanism of formation of phytoene and the series of desaturation reactions by which phytoene is converted into lycopene, and also describes in detail the biosynthesis of bacterial C30 carotenoids. The second paper" presents details of the mechanism and stereochemistry of cyclization and the other reactions that involve the carotenoid C-1 —C-2 double bond and the later modifications, especially the introduction of oxygen functions. 

Mechanism and stereochemistry of reductions of ketones, 66 Mechanism of dehydrohalogenation, 292 Mechanism of hydrogenation, 111 Mechanism of reduction of aromatic compounds, 12... 

The mechanism and stereochemistry of halogenation, physical methods / 273 Dihalogenation / 276 The use of A-halo compounds / 280 The use of other reagents / 282 The oxidation of halohydrins / 283 Vinylogous a-halo ketones / 284... 

II. Vicinal Fluorohydrins / 425 Choice of reagents / 425 Mechanism and stereochemistry / 432 Experimental procedures / 433... 

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