Isomerizations of allylic alcohols

The metal catalysis method has been used for the preparation of simple enols, for example, by isomerization of allylic alcohols. These enols are stable enough for isolation (see p. 75), but slowly tautomerize to the aldehyde or ketone, with half-lives ranging from 40-50 min to several days. ... 

Scheme 53 Transition metal catalyzed isomerization of allylic alcohols...

Drivers Ibr Performing Isomerization of Allyl Alcohols in Micro Reactors... 

Beneficial Micro Reactor Properties for Isomerization of Allyl Alcohols... 

Isomerization of Allyl Alcohols Investigated in Micro Reactors Organic synthesis 41 [OS 41] Isomerization of diverse substituted allyl alcohols OH O... 

The isomerization of allylic alcohols provides an enol (or enolate) intermediate, which tautomerizes to afford the saturated carbonyl compound (Equation (8)). The isomerization of allylic alcohols to saturated carbonyl compounds is a useful synthetic process with high atom economy, which eliminates conventional two-step sequential oxidation and reduction.25,26 A catalytic one-step transformation, which is equivalent to an internal reduction/oxidation process, is a conceptually attractive strategy due to easy access to allylic alcohols.27-29 A variety of transition metal complexes have been employed for the isomerization of allylic alcohols, as shown below. 

Iron complex-catalyzed isomerization of allylic alcohols was found during the studies on the hydrolysis of 7t-allyliron tricarbonyl salts. The isomerization of allyl alcohol to propionaldehyde was observed on heating in the presence of Fe(CO)s (Equation (9)).30... 

The scope and limitations of the Fe(CO)s-catalyzed isomerization of allylic alcohols was investigated in detail. This study revealed that the treatment of secondary allylic alcohols with 10-20 mol% Fe(CO)s at 110-125 °C for 2-6 h gave isomerized ketones in 60-80% yield with >95% purity.31... 

Although the isomerization of allylic alcohols can be catalyzed by Fe(CO)s under thermal conditions, this reaction suffers from slow reaction rates, low yields, and high reaction temperature. To overcome these problems, photochemical activation of Fe(CO)s was investigated. By employing photochemical activation conditions, the isomerization of a wide variety of allylic alcohols proceeded in good to excellent yields using 1-10 mol% of Fe(CO)s in pentane (Scheme 9).32... 

Nickel complexes are also active catalyst for the isomerization of allylic alcohols. Ni(dppb)2, prepared by mixing Ni(cod)2/2dppb (2equiv.), catalyzed the isomerization of geraniol to citronellal in the presence of CF3C02H (4equiv.) in toluene at 80 °C (Equation (10)).34... 

Various ruthenium complexes catalyze the isomerization of allylic alcohols to saturated carbonyl compounds. Ru(acac)3 is an effective catalyst for the isomerization of a wide range of allylic alcohols (Scheme 12).35... 

High chemoselectivity is observed in this ruthenium-catalyzed isomerization of allylic alcohols. Simple primary and secondary alcohols and isolated double bonds are not affected by these catalysts. Furthermore, free hydroxy group is essential for this catalysis. The reaction of l-acetoxycyclododec-2-ene-4-ol furnished 4-acetoxycyclododecanone in high yield (Scheme 14).37... 

The plausible mechanism of this ruthenium-catalyzed isomerization of allylic alcohols is shown in Scheme 15. This reaction proceeds via dehydrogenation of an allylic alcohol to the corresponding unsaturated carbonyl compound followed by re-addition of the metal hydride to the double bond. This mechanism involves dissociation of one phosphine ligand. Indeed, the replacement of two triphenylphosphines by various bidentate ligands led to a significant decrease in the reactivity.37... 

Run(H20)6(tos)2 is an efficient catalyst for the isomerization of allylic alcohols and allylic ethers under mild conditions in aqueous media to yield the corresponding carbonyl compounds.39... 

In parallel to the asymmetric catalytic isomerization of allylamines, [Rh(BINAP) (solvent)2]C104 is a very efficient catalyst for the isomerization of allylic alcohols.9,11 By employing 0.5mol% of the catalyst, good to excellent conversions were achieved even in the case of substrates that are more difficult to isomerize, such as allylic alcohols having two alkyl groups in the terminal position (R1 = R2 = Me) and 2-cyclohexen-l-ol (Scheme 19). 

A very extensive and detailed study of the cationic rhodium(i)-catalyzed isomerization of allylic alcohols demonstrated that mono- and disubstituted allylic alcohols can be efficiently isomerized to the corresponding carbonyl compounds through the corresponding enol compounds (Scheme 20).45 The isomerization using cationic rhodium(l)... 

The mechanistic study revealed that the isomerization of allylic alcohols to the corresponding enols proceeds through a 7r-allyl intermediate (Scheme 21), and the isomerization of the enols to the corresponding carbonyl compounds proceeds through an oxy-7r-allyl intermediate (Scheme 22).45... 

As part of a search for catalysts that can be used under biphasic conditions, zwitterionic Rh(sulphos)(cod) derivatives were studied. The isomerization of allyl alcohol proceeded within 1 h at 100 °C using only 1 mol% catalyst to give propanal in quantitative yield (Equation (12)).46 After separation of the product, the catalyst could be recycled three times with a slight deactivation after each run. 

Although the asymmetric isomerization of allylamines has been successfully accomplished by the use of a cationic rhodium(l)/BINAP complex, the corresponding reaction starting from allylic alcohols has had a limited success. In principle, the enantioselective isomerization of allylic alcohols to optically active aldehydes is more advantageous because of its high atom economy, which can eliminate the hydrolysis step of the corresponding enamines obtained by the isomerization of allylamines (Scheme 26). 

The first enantioselective isomerization of allylic alcohols was carried out by using RhH(CO)(PPh3)3/(—)-DIOP. However, the enantioselectivity was very low (Equation (14)).50... 

The enantioselective isomerization of allylic alcohols using cationic rhodium(l)/BINAP complex was reported.9,11 Although the enantioselectivities were lower than those achieved by the isomerization of the corresponding enamines, 3,3 -disubstituted allylic alcohols were isomerized to the corresponding aldehydes in moderate yield and enantioselectivity (Scheme 27). 

A ruthenium(n)-indenyl complex, which is an efficient catalyst for the isomerization of allylic alcohols, is also an effective catalyst for the isomerization of propargylic alcohols to both a,/3-enals and a,/ -enones (Scheme 57).96 In this reaction, the addition of 20—40 mol% InClj is highly effective. The reaction exhibits extraordinary chemoselectivity and a variety of functional groups are unaffected, which allows a highly efficient synthesis of dienals (R1 =Me2C = CH, R2 = H). 

Metal-catalyzed C-H bond formation through isomerization, especially asymmetric variant of that, is highly useful in organic synthesis. The most successful example is no doubt the enantioselective isomerization of allylamines catalyzed by Rh(i)/TolBINAP complex, which was applied to the industrial synthesis of (—)-menthol. A highly enantioselective isomerization of allylic alcohols was also developed using Rh(l)/phosphaferrocene complex. Despite these successful examples, an enantioselective isomerization of unfunctionalized alkenes and metal-catalyzed isomerization of acetylenic triple bonds has not been extensively studied. Future developments of new catalysts and ligands for these reactions will enhance the synthetic utility of the metal-catalyzed isomerization reaction. 

Some support for the allylic shift pictured above comes from the work of Goetz and Orchin (23) on the isomerization of allyl alcohol to propionaldehyde by DCo(CO)4. These authors found that in the deuterated aldehyde all the D was on the methyl carbon and the following reaction path was suggested ... 

Ordinarily, DCo(CO)4 would be expected to add to an olefin to an appreciable extent by anti-Markownikoff addition, since with olefins more straight chain than branched chain product results. Such addition would place deuterium on the penultimate carbon atom. It can be argued that allyl alcohol is not an olefin and therefore might be expected to behave differently. As usual more work is necessary. A similar isomerization of allyl alcohol to propanal using FelCO) has been reported by Emerson and Pettit (24). 

In support of this mechanism, it was shown that allyl alcohol on treatment with Fe(CO)j is isomerized to propionaldehyde. The identical isomerization of allyl alcohol has been demonstrated (23) to proceed by HCo(CO)4 catalysis and evidence secured for a similar 1,3 or allylic hydrogen shift [Eq. (11)]. 

A recent study has indicated that the skeletal rearrangement step in the B12-catalysed isomerization of methylmalonyl-CoA to succinyl-CoA occurs not by a radical pathway but by an anionic or organocobalt pathway. A computational study of the isomerization of allyl alcohol into homoallyl alcohol by lithium amide has pointed to a process proceeding via a transition state in which the proton is half transferred between carbon and nitrogen in a hetero-dimer. l,l-Dilithio-2,2-diphenylethene... 

As for allylic ethers, there are relatively few reports of highly enantioselective rhodium-catalyzed isomerizations of allylic alcohols (for example, >80% ee). Relative to the other processes described above, reactions of allylic alcohols are more atom economical [6] since they obviate the need for a separate hydrolysis step (Eq. 5). 

For Rh(I)/BINAP-catalyzed isomerizations of allylic amines, the mechanistic scheme outlined in Eq. (2) has been proposed. The available data are consistent with the notion that Rh(I)/PF-P(o-Tol)2-catalyzed isomerizations of allylic alcohols follow a related pathway [11]. For example, the only deuterium-containing product of the reaction depicted in Eq. (9) is the l,3-dideuterated aldehyde, which estabhshes that the isomerization involves a clean intramolecular 1,3-migration. The data illustrated in Eqs. (10) and (11) reveal that the catalyst selectively abstracts one of the enantiotopic hydrogens/ deuteriums alpha to the hydroxyl group. 

One of the landmark achievements in the area of enantioselective catalysis has been the development of a large-scale commercial application of the Rh(I)/BINAP-catalyzed asymmetric isomerization of allylic amines to enamines. Unfortunately, methods for the isomerization of other families of olefins have not yet reached a comparable level of sophistication. However, since the early 1990s promising catalyst systems have been described for enantioselective isomerizations of allylic alcohols and aUylic ethers. In view of the utility of catalytic asymmetric olefin isomerization reactions, I have no doubt that the coming years will witness additional exciting progress in the development of highly effective catalysts for these and related substrates. 

The metal catalysis method has been used for the preparation of simple enols, by isomerization of allylic alcohols, e.g.,71a... 

Rearrangement of allylic alcohols. RuClj in combination with NaOH is a useful catalyst for isomerization of allylic alcohols of the type RCIIOHClI=CH2 to saturated ketones, RCOCH2CH3. In the isomerization of a chiral allylic alcohol such as I, the product is optically active. The 1,3-hydrogen transfer is 37% stereoselective. 

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