Allyl alcohols epimerization

In all cases examined the ( )-isomers of the allylic alcohols reacted satisfactorily in the asymmetric epoxidation step, whereas the epoxidations of the (Z)-isomers were intolerably slow or nonstereoselective. The eryfhro-isomers obtained from the ( )-allylic alcohols may, however, be epimerized in 95% yield to the more stable tlireo-isomers by treatment of the acetonides with potassium carbonate (6a). The competitive -elimination is suppressed by the acetonide protecting group because it maintains orthogonality between the enolate 7i-system and the 8-alkoxy group (cf the Baldwin rules, p. 316). 

The simple and elegant tactic of cleaving the acetoxythioacetal function in 29 either with or without concomitant epimerization at C-2 effectively avoids the problematic (nonstereoselective) epoxi-dation of chiral Z allylic alcohols such as 12-Z (see Scheme 9). 

The aldehyde function at C-85 in 25 is unmasked by oxidative hydrolysis of the thioacetal group (I2, NaHCOs) (98 % yield), and the resulting aldehyde 26 is coupled to Z-iodoolefin 10 by a NiCh/CrCH-mediated process to afford a ca. 3 2 mixture of diaste-reoisomeric allylic alcohols 27, epimeric at C-85 (90 % yield). The low stereoselectivity of this coupling reaction is, of course, inconsequential, since the next operation involves oxidation [pyridinium dichromate (PDC)] to the corresponding enone and. olefination with methylene triphenylphosphorane to furnish the desired diene system (70-75% overall yield from dithioacetal 9). Deprotection of the C-77 primary hydroxyl group by mild acid hydrolysis (PPTS, MeOH-ClHhCh), followed by Swem oxidation, then leads to the C77-C115 aldehyde 28 in excellent overall yield. 

The beneficial effect of fluorine atoms on hydrolytic stability has been demonstrated with synthetic prostaglandin (SC-46275). This compound possesses an antisecretory activity that protects the stomach mucous membrane. However, its clinical development was too problematic because of the instability of the tertiary allyl alcohol function in acidic media (epimerization, dehydration, etc). A fluorine atom has been introduced on the C-16 methyl to inhibit the formation of the allylic carbocation (Figure 4.39). The fluoroanalogue possesses the same biological activity but does not undergo any degradation or rearrangement, and it epimerizes only slowly. 

Epimeric 15-benzoates 9 and 10, derived from the intermediates in prostaglandin synthesis, follow the above mentioned relation of the Cotton effect to the allylic alcohol configuration150. 

On another front, the mixture of allylic alcohols 512 and 513 was converted by reaction with methanesulfonic acid anhydride in the presence of triethylamine to a mixture of the corresponding mesylates, which were subjected collectively to methanolysis to afford 514, and none of the allylic ether epimeric at C-3 was isolated. N Debenzylation of 514 followed by a classic Pictet-Spengler cyclization then afforded ( )-buphanisine (361) (208). 

The quaternary center was constructed stereospecifically by Claisen rearrangement (Scheme 46). The necessary enol ether was obtained by reaction of the secondary alcohol of 399 with ethyl vinyl ether and mercuric acetate. To change the polarity of the endocyclic double bond, the unsaturated ketone was reduced with lithium aluminum hydride to the allylic alcohol, 400, at low temperature. Then, prolonged heating with xylene led to the aldehyde, 401. Protection of the secondary alcohol was achieved by bromoether formation with W-bromosuccinimide in acetonitrile before the aldehyde of 402 was reacted with methyllithium. The epimeric mixture of secondary alcohols was protected as acetates 403. Then, the cyclic ketone... 

Oxidation of -substituted allylic sulfides with 3-chloroperoxybenzoic acid or periodate usually yields S-epimeric sulfoxides, which can be directly subjected to the rearrangement to give optically active allyl alcohols. The enantiomeric excess is determined by the preference of the transoid transition state over the cisoid transition state. 

Spirolactone moieties are important components of some biologically active steroids that possess antitumor activity. A prelude to formation of the spiro unit is the introduction of an allyl side chain into a steroidal ketone. This reaction can be accomplished in good yield by the Barbier reaction of allyl bromide, ketone, and iodine-activated magnesium in ether. With 5a-cholestan-3-one, 51 and 48% of the epimeric allyl alcohols are isolated. With 3(i-(tetrahydropyran-2-yloxy)-5a-androstan-17-one, 98% of the allyl alcohol is isolated [39]. 

Other examples of directed epimerization of allyl alcohols by such processes are known, e.g. in the case of the bicyclic system (8) an exo to endo ratio of 8 to 1 was obtained starting from the more accessible endo-alcohol (8 equation 17). ... 

In the stereoselective total synthesis of ( )-14-deoxyisoamijiol by G. Majetich et al., the last step was the epimerization of the C2 secondary allylic alcohol functionality. The Mitsunobu reaction resulted only in a poor yield (30%) of the inverted product, so the well-established sulfoxide-sulfenate rearrangement was utilized. The allyic alcohol was first treated with benzenesulfenyl chloride, which afforded the thermodynamically more stable epimeric sulfenate ester via an allylic sulfoxide intermediate. The addition of trimethyl phosphite shifted the equilibrium to the right by consuming the desired epimeric sulfenate ester and produced the natural product. 

Oxidation reactions often produce reactive functional groups that can engage in further reactions with various nucleophiles. For example, the allylic epoxidation of 574 using VO(acac)2/t-BuOOH in toluene provided a mixture of 575 and 576 in 40 and 44% yields, respectively (Scheme 96) (04TL6349). Formation of 576 occurred by the spontaneous cyclization of the initially formed epoxide 577. Cyclization of 575 was initiated by the action of TFA to give 578 in 82% yield. The epimeric allylic alcohol 579 reacted in a similar fashion. 

Johnson and Schaaf4 applied the method of CF3C02H-cyclization of polyole-finic allyl alcohols to the tetraenol (16) and obtained the two 13-epimeric alcohols (17) and (18) of the podocarpanc series. 

Structure CXXXVTI is compatible with several miscellaneous reactions and properties of tazettine. It accounts for the production of phenanthridine derivatives by zinc dust distillation (128a) and Oppen-auer oxidation (55) more satisfactorily than CXXXII. The double bond of tazettine is sufficiently removed from the nitrogen atom to have no effect on the basicity of the alkaloid. The allylic methyl ether may be cleaved with hydrochloric acid to a mixture of two epimeric allylic alcohols, tazettinol (CLI) and isotazettinol (CLII). Methylation of tazettinol afforded 0-methyltazettine methiodide, identical with that obtained by the methylation of tazettine. Under similar conditions, isotazettinol afforded the epimeric 0-methylisotazettine methiodide. Both methiodides gave 2-(4-methoxyphenyl)-4,5-methylenedioxyben-... 

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