Allyl alcohol moieties

Ti compounds also promote epoxidation of olefins, mainly allyl alcohol moieties in the presence of peroxides (Scheme 32).1 5... 

Similarly, allenes [32] and alkynols [33] were used as starting materials and their carbonylation provides /3,y-unsaturated acids and unsaturated diacids, respectively. The specific reactivity of alkynols is explained by three formal steps during nickel catalysis (i) carbonylation of the triple bond leading to an acid containing an allylic alcohol moiety (ii) second carbonylation of the double bond to provide a hydroxydiacid and (iii) a dehydration step giving the corresponding unsaturated diacid (Scheme 2). 

An example of a structural substituent that is often metabolized (bioactivated) to an electrophile is the allyl alcohol substituent (C=C—C—OH). Allyl alcohol moieties are found in many commercial chemical substances, either as the free alcohol or as an ester or ether. As illustrated in Scheme 4.1, allyl alcohols (and also as their esters or ethers) that contain at least one hydrogen atom on the alcoholic carbon can be oxidized in the liver by alcohol dehydrogenase (ALDH) to the corresponding a, 3-unsaturated carbonyl metabolite, which is toxic in many cases [29-31]. The hepatotoxicity of allyl alcohol (1), for example, is due to its oxidation by ALDH to acrolein (2), an a,(3-unsaturated aldehyde, which undergoes Michael addition with cellular nucleophiles in the liver [29] (Scheme 4.1). Cyclic allyl alcohols (Scheme 4.1) are expected to undergo similar enzymatic oxidation to yield a,(3-unsaturatcd carbonyl metabolites and are also likely to be toxic. 

The allyloxy radicals generated from hydroperoxide, dialkyl peroxide and cyclic peroxide intermediates, in accordance with Reactions 6, 9, and 10, respectively, are converted to allyl alcohol moieties, as shown in Reaction 7. The latter are particularly susceptible to reaction with hydrogen chloride. 

In conclusion, a Sharpless asymmetric epoxidation reaction may be used to achieve regioselectivity in a complex molecule containing two allylic alcohol moieties with opposite topicity. Thus, 32 could be alternatively converted into laulimalide (1) and its C-20 regioisomer simply by switching the chiral additive from +)- R,R)- to -)- S,S)-diisopropyl tartrate (DIPT). Biological tests have shown that the natural compound 1 is by far the most active one compared to other derivatives such as the C-20 regioisomer. 

The primary alcohol is oxidized to the corresponding aldehyde. Simultaneously, the allylic alcohol moiety is oxidized to an a,p-unsaturated ketone. 

L-Arcanose and L-olimycose have been prepared in enantiomerically pure forms and with high stereoselectivity by Lewis-acid promoted addition of (5)-2-benzyloxypropanal to 1-tri-methylsilyl-2,3-butadiene. Depending on the nature of the Lewis acid either the syn (with TiCl4) or the anti adduct (with BF3 Et20) can be obtained. Epoxidation with lateral control by the allylic alcohol moieties and standard reactions lead to the unprotected monosaccharides [334]. Total syntheses of 2,3-dideoxy-3-C-methyl-D-maw o-heptose and of 2,3-dideoxy-2,3-di-C-methyl-D-gfycero-D-ga(acto-heptose have been realized by addition of 2-(trimethylsiloxy)furan to 2,3-0-isopropylidene-D-glyceraldehyde ((R)-37) [335]. 

For the elaboration of the dienyl side-chain of the E-F fragment of (+)-spongistatin 2, A.B. Smith et al. oxidized the sensitive primary allylic alcohol moiety using the Dess-Martin oxidation. The resulting a,p-unsaturated aldehyde was treated with a Wittig reagent to obtain the desired 1,3-dienyl side chain. 

Oxidation with lead dioxide in 5% phosphoric acid yielded acetaldehyde and formaldehyde. Catalytic reduction in the presence of platinum resulted in the absorption of 1.5 mole equivalents of hydrogen and the isolation, by its steam volatility, of nearly 0.6 mole of a-methylbutyric acid. The carbon skeleton of sarracinic acid was thus determined, and the accompanying hydrogenolysis (some nonvolatile acid was also obtained) established that the double bond and hydroxyl constituted an allylic alcohol moiety. Since further data (spectroscopic data would be especially valuable) were not available, Danilova and Kuzovkov (127) were limited to the conclusion that sarracinic acid could be represented by one of three possible structures (CLXIa-c) ... 

Acyclic Claisen Systems Containing a Secondary Allylic Alcohol Moiety... 

Further branching in the side chain of the allylic alcohol moiety gives rise to enhanced selectivities. For example, the rearrangement of 3,5-dimethyl-l-hexen-3-ol yields a 70 30 EjZ mixture of 2.5,7-trimethyl-4-octenal154. 

Both diastereomers 5 and 6 have exclusively E configuration. This requires the branched side chain of the tertiary allylic alcohol moiety of 4 to occupy the equatorial position. The diastereomeric ratio derives from the enolization stereoselectivity. For a less selective example see also ref 30. 

Enhanced selectivities are also observed in the rearrangements of substrates with a tertiary allylic alcohol moiety 5357,358, 5359,360 7359 and 8357. For the mercury(II)-catalyzed rearrangement of allylic carbamates see ref 358. 

In contrast to allyl N-phenylimidates N-phenyl-/V-silylimidates 4 with an E-allylic alcohol moiety [in the case of 4d (Z)-substrates note that the change in the stereochemical descriptor is only based on the CIP rules] again afford au/t-anilides 5, while. sivt-products 6 arc obtained from the corresponding (Z)-isomers251-463. The rearrangement of the ( )-isomer proceeds smoothly at room temperature, whereas the (Z)-isomers require at least the temperature of refluxing tetrahydrofuran. 

The rearrangement of ester enolates (Ireland rearrangement)36 41 87,88-91-257,292 467-469 derived from allyl esters is perhaps the most flexible Claisen variation, allowing the diasiereo-and enantioselective controlled synthesis of y.fS-unsaturated acids either by a change of the double-bond configuration of the allylic alcohol moiety or variation of the solvent system. 

In comparison to glycolate esters derived from primary allylic alcohols, esters with a secondary allylic alcohol moiety give enhanced selectivities (Table 13, entries 7-13). The increase in the diastereoselectivity has been attributed to the greater steric demand thus favoring the chairlike transition state. 

The Corey-Kim protocol was successfully applied late in the multi-step total synthesis of ingenol (51) to convert diol 49 to a-ketol 50 where it was the less hindered hydroxyl group that was selectively oxidized.14 The newly formed ketone was then used to construct the allylic alcohol moiety of ingenol after several steps. 

Alkynes are useful partners in cationic cyclization reactions. Initial reaction of the allylic alcohol moiety in 91 with formic acid gave allyl cation 92. Subsequent attack by the alkyne moiety across the molecule generated vinyl cation 93. This cation trapped formate anion to generate a formate enol ester (C=C—OCHO). Hydrolysis liberated the final ketone product 94, which Lansbury converted to damsinic acid. ... 

The next and particularly crucial phase of the synthesis was the construction of the quaternary carbon center associated with galanthamine as well as the formation of the furan or B-ring. While it took some time to establish the right sequence of reactions to realize such an outcome, this was eventually achieved in just three steps (Scheme 4). The first was the engagement of the allylic alcohol moiety within compound 15 in an Eschenmoser-Claisen (EC) rearrangement by treating it with the dimethyl acetal of... 

Gaudin, J.-M. (1991) Intramolecular Heck reaction with substrates possessing an allylic alcohol moiety. Tetrahedron Lett., 32, 6113-6. 

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