Allylic alcohols transposition

En route to a total synthesis of the anticancer compound FR901464, Koide and coworkers carried out a diastereoselective allylic selenoxide rearrangement upon oxidation of either allyl selenide 251 [Scheme 18.641. Optimization studies using the preformed allyl selenide 251 identified the o-nitrophenyl selenide as an effective aryl substituent and N,N-dimethylaminopyridine as the best selenophilic base additive in the formation of rearrangement product 252 (see top of Scheme 18.641. Reactions were slower and diastereoselectivity, a crucial parameter here, was lower using other bases or with less than 3 equiv of DMAP. Using the optimized conditions, a one-pot method for overall 1,3-allylic alcohol transposition was... 

The allylic hydroperoxides generated by singlet oxygen oxidation are normally reduced to the corresponding allylic alcohol. The net synthetic transformation is then formation of an allylic alcohol with transposition of the double bond. 

A valuable alternative for enhancing the selectivity is based on telluride-mediated transposition applied to the fran -allylic alcohols." ... 

The transposition of the C=C bond and the alcohol functionality is highly stereospecific, erythro-g yciAo sulphonates giving cA-allylic alcohols and the f/ireo-isomer the trans-allylic alcohol. 

The first example of chemoenzymatic DKR of allylic alcohol derivatives was reported by Williams et al. [37]. Cyclic allylic acetates were deracemized by combining a lipase-catalyzed hydrolysis with a racemization via transposition of the acetate group, catalyzed by a Pd(II) complex. Despite a limitation of the process, i.e. long reaction times (19 days), this work was a significant step forward in the combination of enzymes and metals in one pot Some years later, Kim et al. considerably improved the DKR of allylic acetates using a Pd(0) complex for the racemization, which occurs through Tt-allyl(palladium) intermediates. The transesterification is catalyzed by a lipase (Candida antarctica lipase B, CALB) using isopropanol as acyl acceptor (Scheme 5.19) [38]. 

Enone transposition. A new method for this transposition depends on the regio- and stereoselectivity of addition of C6HsSeCI to allylic alcohols. An example is shown in equation (I). 

Details for the use of cncsilylation for 1,2-transposition of ketones (8, 289-290) have been published.2 The paper includes the conversion of vinylsilanes to rearranged allylic alcohols. The trimcthylsilyl group directs the cnc reaction with singlet oxygen exclusively to the a-position. A typical reaction is shown in equation... 

For reduction of allylic alcohols with double bond transposition, see page 229, Section 4. 

Sometimes, tertiary allylic alcohols interfere with the oxidation of primary and secondary alcohols with PDC, causing low-yielding transformations into the desired aldehydes and ketones.161 Secondary allylic alcohols occasionally suffer oxidative transposition to enones rather than a direct oxidation.162... 

PDC has a lesser tendency to effect oxidative transposition of allylic alcohols than other chromium-based reagents.163... 

This oxidative transposition of tertiary allylic alcohols into enones or enals is carried out under mild conditions and has ample application in organic synthesis. Although, it can be carried out with other chromium-based reagents (see pages 16 and 35), PCC is the reagent of choice.272... 

Although the PCC-mediated oxidative transposition of tertiary allylic alcohols is carried out under very mild conditions, normally it is possible to selectively oxidize a primary or secondary alcohol to aldehyde or ketone with PCC, without affecting a tertiary allylic alcohol present in the same molecule.273... 

Of course, using excess of PCC allows the operation of both, an oxidative transposition of a tertiary allylic alcohol and a normal oxidation of a primary or a secondary alcohol.276... 

The oxidation with PCC causes both, a normal oxidation of the primary alcohol and an oxidative transposition of the tertiary allylic alcohol. 

Although secondary allylic alcohols can suffer an oxidative transposition via the corresponding allylic chromate ester, in the same manner that the tertiary allylic alcohols normally, a direct oxidation to the corresponding enone with no transposition predominates.277 Nevertheless, minor amounts of enone, resulting from an oxidative transposition, can be formed.278 The formation of transposed enone may be minimized using the less transposing-prone PDC, instead of PCC.279... 

When the oxidative transposition of secondary allylic alcohols is purposefully looked after, it can be fostered by the addition of p-toluenesulfonic acid.280 Most probably, the added acid catalyzes the equilibration of the intermediate allylic chromate esters, allowing the major formation of transposed enone when the corresponding chromate ester is less hindered. This means that an oxidative transposition of a secondary allylic alcohol can only dominate when the thermodynamics of the equilibrating allylic chromate esters are favourable. 

Very hindered secondary allylic alcohols may have a great tendency to suffer oxidative transpositions, even without the help of added acid a fact undoubtedly due to the release of steric tension, resulting from the transposition of the initially formed chromate ester.281... 

The authors of this book are not aware of any case, in which a primary allylic alcohol suffers an oxidative transposition with PCC. Such case would be most unlikely, because it would involve an equilibrating pair of allylic chromate ester, in which the less stable minor one would evolve to a carbonyl compound. 

The Overman Rearrangement allows the conversion of readily available allylic alcohols into allylic amines by a two-step synthesis involving the rearrangement of an allylic trichloroacetimidate to an allylic trichloroacetamide with clean 1,3-transposition of the alkenyl moiety. 

It is possible to perform selenenylation-deselenenylation sequences with only catalytic amounts of selenium species. This reaction sequence provides double bond transpositioned allylic ethers, allylic esters, or allylic alcohols 240 from the corresponding alkenes (Scheme 71). This sequence can be performed electrochemically, and the selenium electrophile is generated from catalytic amounts of diphenyl diselenide.467,468 It has been shown that the electrophilic selenium species can also be generated using diselenides and peroxosulfates together with copper (ii)... 

Carbonyl transposition.1 Tetrafluoroboric acid is the most effective acid for rearrangement of a-hydroxy ketene dithioketals to a,p-unsaturated thiol esters. This rearrangement is particularly useful for rearrangement of the tertiary allylic alcohols formed by addition of organometallic reagents to a-keto ketene dithioketals, which are readily available by reaction of ketone enolates with carbon disulfide followed by alkylation with methyl iodide. 

This chemistry forms the basis of a general method for 1,3-hydroxy transposition in allylic alcohols (equation 7). The starting alcohol is converted by 3,3-sigmatropic rearrangement of the 0-allyl-S-methyldithiocarbonate followed by hydrostannolysis to the allylic stannane, which is oxidized by MCPBA in a completely regiospecific manner. A similar sequence has been reported for allylsilanes. "... 

Besides oxidation reactions, MTO supported on AI2O3/ Si02, niobia, or zeolites also catalyzes the metathesis of functionalized alkenes, 1,2 transposition of allylic alcohols, addition of epoxides to ketones, alkoxylation of epoxides, dehydration and amination of alcohols, and... 

The oxidative rearrangement of allylic alcohols to a -unsaturated ketones or aldehydes is one of the most widely used synthetic reactions in this group, and forms part of a 1,3-carbonyl transposition sequence. Scheme 7 shows this reaction and the related conversion of the allylic alcohol to an a, -epoxy carbonyl compound. Chromate reagents induce some allylic alcohol substrates to undergo a dirMted epoxidation of the alkene without rearrangement, but this reaction is beyond the scope of the present discussion. 

Entries 1 and 2 in Table 8 are examples of an overall antarafacial 1,3-transposition of a hydroxy group by selenium compounds20,21. Treatment of the alcohols with 2-nitrophenyl seleno-cyanate in the presence of tributylphosphine gave the selenide with inversion of configuration. Oxidation with hydrogen peroxide led to the selenoxide, which rearranged suprafacially to the allylic alcohol. 

Occasionally, these ring-opening reactions can be used in tandem with other chemical processes, such as oxidation <1995T2467>, intramolecular nucleophilic attack leading to azetidines (Equation 4) <1997TL6059>, or 1,3-allylic transposition leading to Z° and y allylic alcohols <1997TL4675>. 

Oxyselenenylation-oxidative deselenenylation (oxyselenenylation-selenoxide elimination) sequence provides the double-bond transpositioned allylic alcohols and ethers from alkenes. Oxyselenenylation of alkenes and its asymmetric... 

Epoxides will fragment if carbanions are formed adjacent to the epoxide ring. Decomposition of the hydrazone of an epoxy ketone in the presence of base may lead to an allylic alcohol (Scheme 2.24). Since the epoxy ketone may be prepared from an unsaturated ketone, this can form part of a sequence for the 1- 3 transposition of an oxygen function. 

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