Hydroxyalkenes

It is possible to make an oxidative cyclization, akin to the one suffered by 5,6-dihydroxyalkenes, starting from 5-hydroxyalkenes.284a 

This is the normal end product when an intermediate secondary alcohol is formed 

However, as the formation of an intermediate simple chromate ester is not as favorable as the generation of the cyclic chromate ester, involved in the oxidation of 5,6-dihydroxyalkenes, this reaction, demands harsher conditions. Therefore, only tertiary 5-hydroxyalkenes may be normally used as starting compounds, otherwise a direct oxidation of the alcohol to an aldehyde or ketone would occur.287 Because of the harsher conditions involved, very often the resulting 1-hydroxyalkyltetrahydrofuran is further oxidized to a y-lactone or to a ketone.288 

Interestingly, in alcohols containing properly positioned alkenes, it is possible to perform a highly stereoselective tandem formation of tetrahy-drofurans.284a 

A tandem formation of two tetrahydrofurans occurs. The resulting alcohol partially suffers an oxidative breakage to a lactone. 

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The effect of the nature of the electrophile on the stereoselectivity of reactions with substrates containing a terminal alkene and an allylic substituent is dramatically illustrated by some recent results with palladium electrophiles.124 Cyclizations of 3-methyl- or 3-phenyl-5-hydroxyalkenes with palladium catalysts proceed with high selectivity (>9 1) for the 2,3-trans isomer (equation 41).50-124 It is suggested that the steric interactions of the palladium-alkene complex affects the stereochemistry of these cyclizations. In some related cyclizations to form tetrahydropyran products (equation 42 and Table 10), reaction with iodine in the presence of sodium bicarbonate gives a different major diastereomer from cyclization with mercury(II) trifluoroacetate or palladium chloride.123... 

Examples of high levels of 1,4-asymmetric induction in kinetically controlled cyclofunctionalizations are rare. Cyclizations of 5-hydroxyalkenes to form 2,5-disubstituted tetrahydrofurans (equation 47) proceed with low selectivity in most cases.lp Exceptions shown in Table 13 are the palladium-catalyzed cy-clization to a trans 2-vinyl system (entry l )30.i04f gjyj cyclization of a 2-phenyl system with mercury(II) chloride to give a preponderance of the cis isomer (entry 2), presumably through equilibration.136 Equilibration with substituents other than phenyl (Me or f-butyl) resulted in much lower selectivity.136-138... 

As the oxidative cyclization of 5-hydroxyalkenes demands quite harsh conditions, normally it is possible to selectively perform a standard oxidation of a primary or secondary alcohol in other part of the molecule.290... 

The oxidation of 5-hydroxyalkenes 235 with rhenium(VII) oxide gives 2-(hydroxymethyl)-tetrahydrofurans 236 the stereoselectivity has been rationalized by an initial [2 + 2] cycloaddition followed by reductive elimination369. The yield and stereoselectivity of such oxidations are the same in both stoichiometric and periodate-catalysed reactions370. 

Hydroxyalkenes 363 have been found to react with Re2(>7 to produce moderate yields of hydroxymethyl tetrahydrofurans 364 with overall vyw-stereoselectivity493. 

A 6-endo-txig selenoetherification of ( )-5-hydroxyalkenes 225 provides /r-2,3-selenides 226, which undergo oxidative elimination upon treatment with H202 to afford 2-aryl-3,4-dihydropyrans 227 in high yield (Scheme 65, Table 4) <2002TL1735>. 

Intramolecular alkoxycarbonylation of 5-hydroxyalkenes allows the preparation of tetrahydro-furanyl derivatives in good yield. Starting from 3-methyl-5-hexen-2-ol (1), a mixture of 2,5-di-substituted tetrahydrofuranyl derivatives is produced, the 2,5-/ran.v-product being the major component of the reaction mixture. This result indicates that the C-3 substituent has little effect on the stereoselectivity42. 

Tctrahydro-2-furanyl)alkanoates by Alkoxycarbonylation of 5-Hydroxyalkenes General Procedure43 ... 

A mixture of 1.0 mmol of the 5-hydroxyalkene, 2.2 mmol of copper(I) chloride and 0.10 mmol of bis(ace-tonitrile)dichloropalladium in 3 mL of CH3OH under carbon monoxide (1.11 bar) is stirred at 23 °C until the reaction is complete (3.5 10 h, TLC monitoring). After removal of the methanol, the residue is triturated with pentane and the pentane solution is concentrated to give the crude organic products. Purification by short-path vacuum distillation provides the cyclization products. The stereochemistry is determined by an analysis of the H-NMR chemical shift of the hydrogen at C-5 this signal is 0.1 -0.2 ppm further downfield when the proton is cis to the ester side chain compared to the trans arrangement. 

Non-ate allylcopper is also useful in the synthesis of 5-hydroxyalkenes from aliyl chlorides and epoxides. 1,2-AminO alcohols are produced from reaction of epoxides with amide cuprate reagents. ... 

The present oxygenation reaction catalyzed by cobalt(II) complex with the combined use of molecular oxygen (Oxidant) and 2-propanol (Reductant) was also applied to several oxidation reactions as secondary alcohols into ketones, the direct preparation of ketones from vinylsilanes, and stereoselective oxidative cyclization of 5-hydroxyalkenes into tetrahydrofuran derivatives.il... 

Ionic Inflate derivatives of nonmetallic elements such as selenium, sulfur, phosphorus, and iodine form an important class of reagents lor organic chemistry. Highly electrophilic phenylselenyl triflate can be used in the cyclization of 5- and 6-hydroxyalkenes, affording the corresponding tetrahydrofurans and pyrans [132] (equation 68). 

Hydroxyalkenes are especially suitable starting materials for the retro-ene reaction since a stable carbonyl compound is then released as product. The retro-ene reaction of /3-hydroxyalkynes, e.g. 13 14, can be used for the preparation of... 

Positive halogen reagents can cyclize y- and 8-hydroxyalkenes to tetrahydro-furan and tetrahydropyran derivatives, respectively.85 Iodocyclization of homoal-lylic alcohols generates 3-iodotetrahydrofiirans when conducted in anhydrous acetonitrile.86 The reactions are stereospecific, with the /(-alcohols generating the irons and the Z-isomer the cis product. These are endo-5 cyclizations, which are preferred to exo-4 reactions. 

Following the results obtained in the intermolecular carbonylation of alkenes in the presence of alcohols, it seemed conceivable that an alkene-bearing alcohol functionality would react in an intramolecular way giving a cyclic ester as the main product. Thus, the carbonylation (also referred to as cyclocarbony-lation as a cyclization occurs simultaneously) of alkenols (or hydroxyalkenes) was investigated for the selective preparation of lactones. 

Wang and Shi have published a detailed study of their fructose-based dioxirane epoxidation catalyst system with hydroxyalkene substrates. The ees obtained were highly pH dependent. The lower enantioselectivity obtained at low pH is attributed to the substantial contribution of direct epoxidation by Oxone. The results obtained with... 

The H-site is formed of clusters ofnon-polar amino acid side chains which provide a highly hydrophobic surface, which, in the absence of a drug substrate is open to bulk solvent Binding of substrates to this site has been shown to relate to increased lipophilicity for substrates (4-hydroxyalkenes). The actual conjugation reaction, with the thiolate anion acting as a nucleophile proceeds via an SN2-type mechanism yielding the deactivated product... 

The toxic products of lipid peroxidation are malondialdehyde, hydroxyalkenals, and lipid peroxides. 

The earliest studies centered on the cyclization of oi-hydroxyalkenes to furan and pyran ring systems (equations 4 and 5).10 The regiochemistry (attack at the more substituted position) was that expected and the yields were only modest. However, modem advances in catalysis should permit much more efficient processes and many older systems probably warrant re-examination. 

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