Hydroxyalkenes, cyclization

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). 

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. 

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... 

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. 

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

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... 

Cyclization of hydroxyalkenes to furanes and pyranes Alkenes suitably substituted by a hydroxyl group undergo cyclization and carbonylation in the presence of PdCl,/ CuCI to pyranes and/or furanes. The preference for five- or six-membered rings depends mainly on the geometry of the alkenc (E)-alkcnes cyclize mainly to pyranes and (Z)-alkenes cyclize mainly to furanes. 

The cyclization of hydroxyalkenes with a Z-configurated double bond (e.g., 9) confirms this result. In fact, the 2,3-tram disposition determines the 2,5-relationship and for the formation of 2-(tetrahydro-2-furanyl)propanoales only one isomer is observed43. 

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. 

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... 

The cross-metathesis of the allylic phosphonate (480) and hydroxyalkenes (481) using the second generation Grubbs catalyst (482) and copper(I) iodide afforded substituted allylic phosphonates (483) in good yields (Scheme 123). Further stereospecific palladium(0)-catalyzed cyclization gave tetrahydrofuran (n = 1) and tetrahydropyran (n = 2) vinyl phosphonates (484). ... 

Reitz AB, Nortey SO, Maryanoff BE, Liotta D, Monahan R HI (1987) Stereoselectivily of electrophile-prmnoted cyclizations of y-hydroxyalkenes. An investigation of carbohydrate-dtaived and model substrates. J Org Chem 52 4197-4202... 

Hydroxyalkenes possessing a nucleophilic group on C-5 cyclize, via palladium-catalysed addition of the nucleophile to the alkene and subsequent carbonylative lactonization to the 3-hydroxy-group, to give bicyclic [3-3-0] systems. This general process has been used to prepare bicyclic bis-lactones, cis-3-hydroxypyrrolidine-... 

Electrophilic iodine reagents have also been employed in iodocyclization. Several salts of pyridine complexes with such as bis(pyridinium)iodonium tetrafluoroborate and bis(collidine)iodonium hexafluorophosphate have proven especially effective. y-Hydroxy- and (3-hydroxyalkenes can be cyclized to tetrahydrofuran and tetrahydropyran derivatives, respectively, by positive halogen reagents. (see entries 6 and 8 in Scheme 4.2). 

Similarly, Schlecht and Kim have reported a substituent-directed oxidation method for the synthesis of 8-lactones by oxidative cyclization of hydroxyalkenes [80] (Scheme 36). Addition of alkenyl Grignard reagent to ketones 184 afforded hydroxyalkene 185, which upon treatment with chromium trioxide in acetic acid and acetic anhydride provided spiro-8-lactone 186. 

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