Transient allylic alcohol

The conversion of 2 and 15 into the corresponding a,p-unsaturated aldehydes 17 has been judged to rely on one or both of the two competing mechanisms depicted in Scheme 5.4. The detection, on some substrates [27, 37], of the transient allylic alcohol 16 clearly suggests that an early PMB group removal followed by a subsequent oxidation in situ of 16 under single electron transfer (SET) conditions [39] may take place (Scheme 5.4A). The latter transformation is supposed to occur via formation of the stabilized cation intermediate 18, overall obtained by H and e abstractions from 16 by DDQ. Similarly, when no allylic alcohol intermediate, even at low temperature, could be detected, a direct oxidative deprotection mechanism has been postulated, involving formation of the hemiacetal intermediate 20 via cation 19 (Scheme 5.4B). 

Dehydrobromination of bromotrifluoropropene affords the more expensive trifluoropropyne [237], which was metallated in situ and trapped with an aldehyde in the TIT group s [238]synthesis of 2,6-dideoxy-6,6,6-trifluorosugars (Eq. 77). Allylic alcohols derived from adducts of this type have been transformed into trifluoromethyl lactones via [3,3] -Claisen rearrangements and subsequent iodolactonisation [239]. Relatively weak bases such as hydroxide anion can be used to perform the dehydrobromination and when the alkyne is generated in the presence of nucleophilic species, addition usually follows. Trifluoromethyl enol ethers were prepared (stereoselectively) in this way (Eq. 78) the key intermediate is presumably a transient vinyl carbanion which protonates before defluorination can occur [240]. Palladium(II)-catalysed alkenylation or aryla-tion then proceeds [241]. 

In early 1993, Haw and co-workers (107) reported in situ studies of allyl alcohol-/-13C on HZSM-5 and CsHX. No persistent carbenium ions were observed, but 1,3 label exchange was observed for the alcohol on the weakly acidic zeolite. We interpreted this as support for a transient allyl cation. The low stability of this cation was invoked to explain the failure to observe this species as a persistent species. Downfield signals observed in that study were attributed to the formation of propanal. Later in 1993, Biaglow, Gorte, and White (BGW) (108) reported similar studies conducted at different loadings and assigned a downfield resonance (variously reported at 216 and 218 ppm by BGW) to the allyl cation in HZSM-5. 

Penttila KE, Makinen J, Lindros KO. 1987. Allyl alcohol liver injury Suppression by ethanol and relation to transient glutathione depletion. Pharmacol Toxicol (Copenhagen) 60 340-344. 

Cookson has studied substrates that can, in principle, effect a tandem Claisen-Cope-Cope rearrangement. By employing 1,1,3-trimethoxybutane as a surrogate for 1-methoxy-1,3-butadiene (equation 10), allylic alcohol (62) undergoes acid-catalyzed exchange to provide the transient p,y-unsaturated aldehyde (66) which, lacking a substituent at the a-position, suffers a facile conjugation of the double bond that preempts the tandem process. This phenomenon has been also observed by Thomas. ... 

Nevertheless, it must be pointed out that the formation of such transient species has never been spectroscopically observed. Native CDs are effective inverse phase-transfer catalysts for the deoxygenation of allylic alcohols, epoxydation,or oxidation " of olefins, reduction of a,/ -unsaturated acids,a-keto ester,conjugated dienes,or aryl alkyl ketones.Interestingly, chemically modified CDs like the partially 0-methylated CDs show a better catalytic activity than native CDs in numerous reactions such as the Wacker oxidation,hydrogenation of aldehydes,Suzuki cross-coupling reaction, hydroformylation, " or hydrocarboxylation of olefins. Methylated /3-CDs were also used successfully to perform substrate-selective reactions in a two-phase system. 

A similar variant of the Claisen rearrangement reacts allyl alcohols such as 600 with 3-bromoselenides (601) to give 602. Oxidation to the transient selenoxide (603) and in situ syn-elimination (sec. 2.9.C.vi) gave 604. This ether possessed the proper functionality for Claisen rearrangement to the final product, ester 605.450 Petrzilka used a variation of this method for the synthesis of phoracantholide J.451... 

N. Selander, A. Kipke, S. Sebehus, K. J. Szab6, J. Am. Chem. Soc. 2007, 129, 13723-13731. Petasis borono-Mannich reaction and allylation of carbonyl compounds via transient allyl boronates generated by palladium-catalyzed substitution of aUyl alcohols. An efficient one-pot route to stereodefmed a-amino acids and homoaUyl alcohols. 

An intermediate of potential use in the synthesis of macrocyclic antibiotics has been obtained starting from allylic and homo-allylic alcohols. The anions generated with BuLi react with carbon dioxide to give the transient anion (60) which cyclizes in the presence of iodine. Functionalization of the double bond is highly regioselective and the equatorial stereochemistry of the 6-membered example (61, n = 1) has been established by n.m.r. spectroscopy. 

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. 

Alkyl cations are thus not directly observed in sulphuric acid systems, because they are transient intermediates present in low concentrations and react with the olefins present in equilibrium. From observations of solvolysis rates for allylic halides (Vernon, 1954), the direct observation of allylic cation equilibria, and the equilibrium constant for the t-butyl alcohol/2-methylpropene system (Taft and Riesz, 1955), the ratio of t-butyl cation to 2-methylpropene in 96% H2SO4 has been calculated to be 10 . Thus, it is evident that sulphuric acid is not a suitable system for the observation of stable alkyl cations. In other acid systems, such as BFj-CHsCOOH in ethylene dichloride, olefins, such as butene, alkylate and undergo hydride transfer producing hydrocarbons and alkylated alkenyl cations as the end products (Roberts, 1965). This behaviour is expected to be quite general in conventional strong acids. 

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