Allylic with tertiary alcohols

The transformation is also possible with hexamethyldisilane and pyridinium bromide perbromide as the source of bromine. This reaction, however, is slower in the case of primary and secondary alcohols. Benzylic, allylic, and tertiary alcohols react rapidly. Hence selective reactions are possible. In the case of secondary alcohols, the conversion occurs with 88% inversion. 

Addition to alkenes.1 Hydrazoic acid adds readily to end ethers to give a-azido ethers. Addition to styrenes and 1,1-disubstituted or trisubstituted alkenes requires a Lewis acid catalyst (TiCl4 or A1C13). Benzylic, allylic, and tertiary alcohols react with HN3-TiCl4 to form azides. 

The reagent formed by reaction of Znij with NaCNBH3 in CHjClj allows the reduction of aromatic aldehydes and ketones as well as benzylic, allylic, and tertiary alcohols to hydrocarbons, probably by a radical process [LDl] (Section 2.4). Some comparable reductions are carried out in ether media starting from tertiary, benzylic, or allylic halides (Section 2.1). 

The AE reaction has been applied to a large number of diverse allylic alcohols. Illustration of the synthetic utility of substrates with a primary alcohol is presented by substitution pattern on the olefin and will follow the format used in previous reviews by Sharpless but with more current examples. Epoxidation of substrates bearing a chiral secondary alcohol is presented in the context of a kinetic resolution or a match versus mismatch with the chiral ligand. Epoxidation of substrates bearing a tertiary alcohol is not presented, as this class of substrate reacts extremely slowly. 

The rearrangement of an ether 1 when treated with a strong base, e.g. an organo-lithium compound RLi, to give an alcohol 3 via the intermediate a-metallated ether 2, is called the Wittig rearrangement. The product obtained is a secondary or tertiary alcohol. R R can be alkyl, aryl and vinyl. Especially suitable substrates are ethers where the intermediate carbanion can be stabilized by one of the substituents R R e.g. benzyl or allyl ethers. 

The relationship between 9 and its predecessor 10 is close. Oxidation of the allylic C-3 methylene group in 10 and elimination of the methoxy group could furnish enone 9. Retrosynthetic disassembly of ring E in 10 furnishes tertiary alcohol 11 as a viable precursor. That treatment of 11 with a catalytic amount of acid will induce the formation of a transient oxonium ion at C-12 which is then intercepted by the appropriately placed C-4 tertiary hydroxyl group is a very reasonable proposition. As we will see, the introduction of the requisite C-4 hydroxyl group is straightforward from intermediate 12. 

The reaction gives good yields with primary, secondary, and tertiary alcohols, and with alkyl and aryllithium reagents.Allylic alcohols also couple with certain... 

The subsequent epoxidation of these in situ formed allylic tertiary alcohols yielded the corresponding syn-e oxy alcohols with high levels of diastereo- and enantioselectivity, thus providing a novel one-pot asymmetric synthesis of acyclic chiral epoxyalcohols via a domino vinylation epoxidation reaction (Scheme 4.17). ... 

Despite the great success of the transmetalation process in the enantiose-lective arylation of ketones, its extension to allylation or alkynylation reactions failed, providing the corresponding tertiary alcohols with enantiomeric excesses never higher than 50% ee. On the other hand, more success has been found in the alkenylation of ketones. The process started with the hydrozirconation of terminal alkynes to give the corresponding alkenylzirconium intermediates, which were transmetalated by reaction, in this case, with various ketones in the presence of the HOCSAC ligand. This protocol tolerated the presence of other carbon-carbon multiple bonds on the alkyne, as well as different functionalities and achieved excellent results for alkyl ketones, a,(3-unsaturated ketones and even dialkylketones, as shown in Scheme 4.22. 

Trifluoromethanesulfonates of alkyl and allylic alcohols can be prepared by reaction with trifluoromethanesulfonic anhydride in halogenated solvents in the presence of pyridine.3 Since the preparation of sulfonate esters does not disturb the C—O bond, problems of rearrangement or racemization do not arise in the ester formation step. However, sensitive sulfonate esters, such as allylic systems, may be subject to reversible ionization reactions, so appropriate precautions must be taken to ensure structural and stereochemical integrity. Tertiary alkyl sulfonates are neither as easily prepared nor as stable as those from primary and secondary alcohols. Under the standard preparative conditions, tertiary alcohols are likely to be converted to the corresponding alkene. 

Normally, the reaction of an ester with one equivalent of a Grignard reagent leads to a mixture of tertiary alcohol, ketone, and unreacted ester. However, when allylic Grignard reagents are used in the presence of one equivalent of LDA, good yields of ketones are obtained. What is the role of the LDA in this process ... 

Allyl Alcohols. Secondary cyclic allylic alcohols are reduced with the combination of Et3SiH and ethereal LiC104, even in the presence of a tertiary alcohol (Eq. 35) or ketal function.173 Primary allylic alcohols do not undergo deoxygenation under similar conditions.173... 

R1 to R3 with yields ranging from 20% to 90%. For the reaction of acetophenone, allyl bromide can be replaced with propargyl bromide, benzyl bromide, or an a-bromoester, affording the corresponding tertiary alcohols in 86%, 86%, and 66% yields, respectively. 

TMEDA and bipyridine also gave the corresponding complexes. Amoung those complexes, only 120 was found to react smoothly with 3-phenylpropanal to give 119 in good yield. When the aldehyde and the acetylene of Scheme 51 were replaced with acetone and dipentylacetylene, respectively, the corresponding allylic tertiary alcohol could be obtained in 83%. 

Addition of l,3-bis(methylthio)allyllithium to aldehydes, ketones, and epoxides followed by mercuric ion-promoted hydrolysis furnishes hydroxyalkyl derivatives of acrolein5 that are otherwise available in lower yield by multistep procedures. For example, addition of 1,3-bis-(methylthio)allyllithium to acetone proceeds in 97% yield to give a tertiary alcohol that is hydrolyzed with mercuric chloride and calcium carbonate to saturated aldehyde.8 Similarly, addition of l,3-bis(methylthio)allyl-lithium to an epoxide, acetylation of the hydroxyl group, and hydrolysis with mercuric chloride and calcium carbonate provides a 5-acetoxy-a,/ -unsaturatcd aldehyde,6 as indicated in Table I. Cyclic cis-epoxides give aldehydes in which the acetoxy group is trans to the 3-oxopropenyl group. 

These results support the /3-elimination from 220 to give 221, towards which KOtBu acts as a base and a nucleophile. As in the case of 215, the addition occurs at the central allene carbon atom leading the allyl anion 222, which is protonated to yield 223. On the other hand, the deprotonation of the methylene group brings about 224, whose major amount is converted to naphthalene, but a small proportion, behaving as a nucleophile, traps 221, giving rise to the allylanion 225, which in turn reacts with 221 and, by a hydride transfer, furnishes 228 and the allyl anion 229. By protonation, the latter is converted into 226. By conducting this experiment in the presence of benzophenone, this mechanistic model was confirmed as the tertiary alcohols 227 and 230 were obtained in addition to naphthalene, 223 and 228. Apparently, the anions 224 and 229 were intercepted in part or totally, respectively, by benzophenone (Scheme 6.52) [137]. 

Next, the TMS enol ether of 53c underwent oxidation with MCPBA to trimethylsilyloxy ketone 57. in 86% yield (86% conversion). Addition of methylmagnesium bromide in methylene chloride proceeded in almost quantitative yield (95%) to give tertiary alcohol 58. Dehydration with Burgess reagent [19] and acidic workup provided the allylic alcohol 59a in 63% yield, which was converted... 

A number of compounds react rapidly with DDQ at room temperature. They include allylic and benzylic alcohols, which can thus be selectively oxidized, and enols and phenols, which undergo coupling reactions or dehydrogenation, depending on their structure. Rapid reaction with DDQ is also often observed in compounds containing activated tertiary hydrogen atoms. The workup described here can be used in all these cases. 

Transition metal-catalyzed allylic substitution with phenols and alcohols represents a fundamentally important cross-coupling reaction for the construction of allylic ethers, which are ubiquitous in a variety of biologically important molecules [44, 45]. While phenols have proven efficient nucleophiles for a variety of intermolecular allylic etherification reactions, alcohols have proven much more challenging nucleophiles, primarily due to their hard, more basic character. This is exemphfied with secondary and tertiary alcohols, and has undoubtedly limited the synthetic utihty of this transformation. 

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