Epimerization double

Ledlie and coworkers have studied the silver ion catalyzed solvolyses of the epimeric double bond containing tertiary propellanes 25 and 26 in methanol. They observed no... 

In acid solution, the double bond of (203) is hydrogenated to the trans-fused sulfone (204). Presumably, this hydrogenation goes through a cis-fused intermediate that is rapidly epimerized to (204) under the acidic conditions of the reaction. Condensation of the sodium salt of 7,7-ethylenedioxy-3-oxooctanoate (205) with (204) produces (206). Cmde (206) is cyclized, hydroly2ed, and decarboxylated, producing the tricycHc compound (207). Hydrogenation of (207) followed by ketal hydrolysis and cyclization affords (208) in an overall yield of 35% from hydrindandione (203). 

Strong bases such as methan olic potassium hydroxide, sodium methoxide, or 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), cause epimerization at the C-2 carbon or shift the beta-gamma double bond into conjugation with the lactone carbonyl (Fig. 4) (25,26). 

Pyridone also catalyzes epimerization of the anomeric position of the tetramethyl ether of glucose. The mechanism involves two double proton transfers. The first leads to a ring-opened intermediate, and the second results in ring closure to the isomerized product ... 

The reductive elimination of halohydrins provides a means of introduction of double bonds in specific locations, particularly as the halohydrin may be obtained from the corresponding a-halo ketone. This route is one way of converting a ketone into an olefin. (The elimination of alcohols obtainable by reduction has been covered above, and other routes will be discussed in sections IX and X.) An advantage of this method is that it is unnecessary to separate the epimeric alcohols obtained on reduction of the a-bromo ketone, since both cis- and tran -bromohydrins give olefins (ref. 185, p. 251, 271 cf. ref. 272). Many examples of this approach have been recorded. (For recent examples, see ref. 176, 227, 228, 242, 273.) The preparation of an-drost-16-ene (123) is illustrative, although there are better routes to this compound. 

Treatment of an epimeric mixture of 4-substituted 2-(trimethylsilyloxy)-5-phenyl-3-phenylthio-l,4-oxazine 264 with ZnBr2 led to the stereoselective formation of perhydropyrido[2,l-c][l,4]oxazine 266 via the iminium ion 265 by the phenyl bearing stereocenter directed addition of the olefinic double bond from the /S-face of the cyclic moiety (97SL799, 98T10309). Similarly, an epimeric mixture of (45,9aS)-l-trimethylsilyloxy-4-phenyl-3,4,6,7-tetra-hydropyrido[2,l-c][l,4]oxazine was prepared by cyclization of (Z)-5(S)-phenyl-3-phenvlsulfanyl-2-trimethylsilyloxy-4-[4-(trimethylsilyl)but-3-enyll morpholine (OOSC2565). 

The final two stages are very straightforward. Oxidative scission of the C3-C5 double bond in 6 with ozone provides triketone 5 which, without purification, is subjected to a base-induced intramolecular aldol/dehydration reaction. The crystalline product obtained from this two-step sequence (45 % overall yield) was actually an 85 15 mixture of ( )-progesterone and a diastereomeric substance, epimeric at C-17. Two recrystallizations afforded racemic progesterone [( )-(1)] in diastereomerically pure form. 

After 12 hours at 4 kbar. this reaction provided only 35% of a 63 27 mixture of 22 and a compound which was tentatively assigned structure 23. It is assumed that 23 derives from epimerization of 21 prior to reaction with (aS,S,S)-5l0b. Whether this stereochemical assignment is correct or not, this result shows that 5 may have problems with configurationally labile aldehydes in demanding cases of mismatched double diastereosclcction. For further examples of double asymmetric induction with 5 or related reagents, see refs 31, 34 and 47. 

Another version of the double [2,3]-sigmatropic rearrangement, involving the sequence sulfenate - sulfoxide - sulfenate, has also been observed. For example, an effective one-pot epimerization procedure of 17a-vinyl-l 7/i-hydroxysteroids to the rather inaccessible 17-epimers has been achieved by the use of such a rearrangement (equation 35)137. Thus treatment of alcohol 76a with benzenesulfenyl chloride afforded the sulfoxide 77 as a single isomer and E-geometry of the olefinic double bond. Exposure of 77 to trimethyl phosphite in refluxing methanol produced a mixture of 76b and 76a in a 73 27 ratio. 

As for the synthesis of 5-e/j/-KDG, compound 6 seemed to be a suitable precursor of the methyl ester of 5-deoxy-KDG 20 since only the C-5 hydroxyl was unprotected. In this case the key step was not the epimerization but the removal of that hydroxyl. Our attempts of radicalar deoxygenation of 6 were unsuccessful because the intermediate radical was intramolecularly trappy by the C-2.C-3 double bound. Therefore we first reduced the double bond and then converted the resulting diastereoisomeric alcohols 14 into the corresponding triflates 15 which were submitted to the action of sodium iodide. Finally the iodides 16 Aus obtained were hydrogenolyzed in the presence of diisopropylethylamin to give 17. 

The cyclization requires that the intermediate have a cis ring fusion. The stereochemistry of the ring junction was established when the double bond was moved into conjugation in Step B-2. The product was not stereochemically characterized, and need not be, because the stereochemically important site at C(l) can be epimerized under the basic cyclization conditions. Thus, the equilibration of the ring junction through a dienol allows the cyclization to proceed to completion from either stereoisomer. 

There was, however, no significant selectivity in the initial hydroboration of the terminal double bond. As a result, both configurations are formed at C(6). This problem was overcome using the epimerization process from Scheme 13.34. 

Formal isomerization of the double bond of testosterone to the 1-position and methylation at the 2-position provides yet another anabolic/androgenic agent. Mannich condensation of the fully saturated androstane derivative 93 with formaldehyde and di-methylamine gives aminoketone 94. A/B-trans steroids normally enolize preferentially toward the 2-position, explaining the regiospecificity of this reaction. Catalytic reduction at elevated temperature affords the 2a-methyl isomer 95. It is not at all unlikely that the reaction proceeds via the 2-methylene intermediate. The observed stereochemistry is no doubt attributable to the fact that the product represents the more stable equatorial isomer. The initial product would be expected to be the p-isomer but this would experience a severe 1,3-diaxial non-bonded interaction and epimerize via the enol. Bromination of the ketone proceeds largely at the tertiary carbon adjacent to the carbonyl (96). Dehydrohalogenation... 

Fry and Newberg 1,2> examined the electrochemical reduction of nor-camphor oxime (109) and camphor oxime (110) to the corresponding amines. The results of this study are shown in Table 3. It is clear from a comparison of these data with those in Table 2 that the electrochemical reduction of oximes 109 and 110 takes a very different stereochemical course from reduction of the corresponding anils 103 and 104. Reduction of oximes apparently proceeds under kinetic control, affords products corresponding to protonation at carbon from the less hindered side of the carbon-nitrogen double bond, and affords the less stable epimeric amine in each case. It is not evident why the stereochemistry of reduction of anils and oximes should differ, however. 

Reduction of the N(ll)=C(lltf) double bond of l,4-dihydro-2//-pyrazino[2,l-A quinazoline-3,6-diones 30 (R1 = indol-3-ylmethyl R2 = Me) and 31 (R1 = CH2-C6H4-C1- z Rz = Me) was effected with NaBH4. While the m-diastereomer, 30, retained its configuration, the /razw-diastereomer, 31, epimerized during the reaction. <1999JOC7233>. 

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