Epimerization rearrangement

Some methods of metal ion-catalyzed chemical and enzymic isomerization (Lobry de Bruyn-Alberda van Ekenstein rearrangement, epimerization at C-2 of aldoses, action of isomerases) of free sugars have been reviewed (136 refs.). ... 

Also in 1993, Hauske and JuUn reported a similar Ireland-Claisen rearrangement of an acyclic C6 carbamate (Scheme 4.35) [39]. The authors examined three different silyl ketene acetals in the rearrangement, although no experimental details were provided. AU three examples apparently proceeded with complete facial selectivity with respect to the allyUc alkene to afford the syn stereochemistry between the aUyl group and the NHBoc group in the conformation shown. The same rationale for facial selectivity can be applied as for Mulzer s results in the previous scheme. The reason for the low C2,C3 synjanti diastereoselectivity in the propionate example was not addressed. A lack of control of enolate geometry or post-rearrangement epimerization are both possible. 

With the exception of the above example, post-rearrangement epimerization is generally an undesired side reaction. McIntosh et al. found that Ireland-Claisen rearrangement of some his-allyUc esters using excess KHMDS and TlPSOTf led to... 

The present authors have noted in compiling this review that there are several examples of unusually low diastereoselectivity in systems that would be expected to give good to high levels of stereoselectivity. It seems likely that, at least in some cases, post-rearrangement epimerization is taking place. 

The most recent, and probably most elegant, process for the asymmetric synthesis of (+)-estrone appHes a tandem Claisen rearrangement and intramolecular ene-reaction (Eig. 23). StereochemicaHy pure (185) is synthesized from (2R)-l,2-0-isopropyhdene-3-butanone in an overall yield of 86% in four chemical steps. Heating a toluene solution of (185), enol ether (187), and 2,6-dimethylphenol to 180°C in a sealed tube for 60 h produces (190) in 76% yield after purification. Ozonolysis of (190) followed by base-catalyzed epimerization of the C8a-hydrogen to a C8P-hydrogen (again similar to conversion of (175) to (176)) produces (184) in 46% yield from (190). Aldehyde (184) was converted to 9,11-dehydroestrone methyl ether (177) as discussed above. The overall yield of 9,11-dehydroestrone methyl ether (177) was 17% in five steps from 6-methoxy-l-tetralone (186) and (185) (201). 

Several ring contraction routes to /3-lactams have been developed. One of the most important is the photochemical Wolff rearrangement of 3-diazopyrrolidine-2,4-diones (178), which provides a general route to 3-carboxyazetidin-2-ones (179). Lack of stereoselectivity is a problem, but facile epimerization is possible because of the electron withdrawing 3-substituent (78T1731). 

In some cases products of rearrangement are obtained either partially or exclusively on treatment of Grignard reagents with epoxides. Thus, reaction of the 2/ ,3/ -epoxide (14) with methyl Grignard reagent affords a mixture of two epimeric secondary A-nor alcohols (15) in 80% yield and the tertiary hydroxy compound, 2a-methyl-5a-cholestan-2/f-ol (16) in 15 % yield. ... 

Oxidation of the hydroxy group in (10) to the ketone followed by isomerization affords the 10oc-methyl-A -3-ketone (11). In contrast, methylenation of 3)5-hydroxy-A ° -compounds proceeds in refluxing ether solution to give, after oxidation and acid rearrangement, the natural 10/5-methyl-A -3-keto steroids. With an epimeric mixture of 3fi- and 3a-A ° -alcohols only the )5-alcohol reacts under these imild conditions. ... 

In general all four possible diastereomers of the a-product are observed and there is evidence to suggest that the ratios of these products arc the result of epimerization of two of the stercogenic centres by a [2,3] sigmatropic rearrangement during workup and handling of the product. 

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. 

Photochemical oxygen transfer reactions involving sulfoxides have also been documented. For example, a photochemical rearrangement of 2-nitrophenyl phenyl sulfoxide to 2-nitrosophenyl phenyl sulfone224, and the inverse photoconversion of o-methylbenzoic acid225 have been reported. Finally, photochemical epimerizations of the sulfoxide centers... 

Enantiomers, preferential crystallization of 59 Endo selectivity 798 Ene reactions 808, 809 Enones, synthesis of 732 Enthalpies of formation 102, 103 Enynes, synthesis of 956 Enzymatic kinetic resolution 829 Epimerization 399 Episulphides, oxidation of 237 Episulphones 650, 775 Episulphoxides, photolysis of 742 a,/J-Epoxysulphones reactions of 811, 812 rearrangement of 685 synthesis of 612 / ,y-Epoxysulphones 781 y,<5-Epoxysulphones 627, 628 Epoxysulphoxides reactions of 613 rearrangement of 744 synthesis of 327, 612 Erythronolides 831... 

Van t Hoff t-factors 565 Vinylallenes rearrangement of 748 synthesis of 737 Vinyl carbonium ions 620 17a-Vinyl-17/f-hydroxysteroids, epimerization of 735 Vinyl sulphides, as alkyl sulphoxide reduction products 930, 932 Vinyl sulphones - see also Alkenyl... 

Finally, the most significant mechanistic feature of the Ramberg-Backlund rearrangement is the stereoselective formation of ds-olefin products, as a result of the preferential cis-positioning of the pair of R groups in the episulfone-forming transition state, variously attributed to London forces , to diastereoselectivity in carbanion formation and to steric attraction . However, with the use of stronger bases such as potassium t-butoxide °, the trans-olefin predominates (equation 52), apparently due to prior epimerization of the kinetically favoured cts-episulfone, and subsequent loss of the sulfur dioxide. Similarly, when the episulfone intermediates possess unusually acidic... 

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