Radical tetrahydropyran

Interesdng intramolecular cycllzadon of Tnitroalkyl radicals generated by one-electron oxidadon of nci-nitro anions vrith CAN is reported. As shown in Eq. 5.44, stereoselecdve formadon of 3,4-funcdonalized tetrahydroflrtans is observed. TNitro-6-heptenyl radicals generated by one electron oxidadon of aci-nitroanions vrith CAN afford 2,3,4-trisnbsdtuted tetrahydropyrans. The requisite nitro compounds are prepared by the Michael addidon of 3-buten-Tal to nitroalkenes. 

As a strategy for the construction of cyclic ethers, the radical cyclization of jS-alkoxyacrylates was used for the preparation of czs-2,5-disubstituted tetrahy-drofurans and cis-2,6-disubstituted tetrahydropyrans. An example is given with S-alkoxymethacrylate 38 as precursor of the optically active benzyl ether of (+)-methyl nonactate, exclusively formed as the threo product (Reaction 44). ° ... 

The base-catalysed ring contraction of 1,3-dioxepanes offers an attractive route to 4-formyl tetrahydropyrans (Scheme 14) , whilst fused exo-cyclic dienes 27 result from the radical cyclisation of alkenyl iodides 26 (Scheme 15) <00OL2011>. Intramolecular radical addition to vinylogous sulfonates is highly stereoselective, leading to the ci s-2,6-disubstituted tetrahydropyran (Scheme 16) . 

The preparation in good yield of (3-mercaptoethylphosphines has been accomplished by the free radical-induced addition of primary and secondary phosphines across the olefinic linkage of 2-(vinylthio)tetrahydropyran.446 The target materials were isolated by hydrolysis of the intermediate substituted thiotetrahydropyran. 

Dilworth, J.R., Griffiths, D.V., Hughes, J.M., and Morton, S., Synthesis of 2-S-(2-tetrahydropyranyl)thioethylphosphines and 2-mercaptoethylphosphines by free radical addition of phosphines to 2-(vinylthio)tetrahydropyran, Phos-ph Sulf, Silic. Relat. Elem., 71, 249, 1992. 

Rychnovsky et al. considered the formation of achiral conformers from chiral molecules and trapping the prochiral radical with a hydrogen atom donor based on memory of chirality (Scheme 12) [41], The photo-decarboxylation of optically active tetrahydropyran 40 leads to an intermediate 43, which now does not contain a stereocenter. If the intermediate 43 can be trapped by some hydrogen atom source before ring inversion takes place, then an optically active product 41 will be formed. This is an example of conformational memory effect in a radical reaction. It was reported that the radical inversion barrier is low (< 0.5 kcal/mol) while the energy for chair flip 43 44 is higher (5 to... 

Some monomers with no tendency toward homopolymerization are found to have some (not high) activity in copolymerization. This behavior is found in cationic copolymerizations of tetrahydropyran, 1,3-dioxane, and 1,4-dioxane with 3,3-bis(chloromethyl)oxetane [Dreyfuss and Dreyfuss, 1969]. These monomers are formally similar in their unusual copolymerization behavior to the radical copolymerization behavior of sterically hindered monomers such as maleic anhydride, stilbene, and diethyl fumarate (Sec. 6-3b-3), but not for the same reason. The copolymerizability of these otherwise unreactive monomers is probably a consequence of the unstable nature of their propagating centers. Consider the copolymerization in which M2 is the cyclic monomer with no tendency to homopolymerize. In homopolymerization, the propagation-depropagation equilibrium for M2 is completely toward... 

Under anhydrous conditions, side reactions due to hydroxyl or perhydroxyl radical species can be avoided. Tetrahydropyran and tetrahydrofuran ethers were prepared in good to excellent yields (85-97%) from the corresponding primary and secondary alcohols and THP and THE as a solvent using (w-Bu4N)2S208. Under these reaction conditions the sulfide group and acid-sensitive groups such as aUylic hydroxyl or an acetal moiety remain intact (equation 27). 

It was reported that Pd(0)-catalyzed coupling reactions of allenic alcohols, amines and acids with hypervalent iodonium salts afforded cyclized heterocyclic tetrahydrofurans, tetrahydropyrans, pyrrolidines, piperidines, or lactones under mild conditions <99SL324>. Intramolecular 1,5-hydrogen atom transfer radical cyclization reaction of pyrrolidine derivatives was examined. Reaction of 3,4-dialiyloxy-JV-(0-bromobenzyl)pyrtolidine gave hexahydro-... 

Unsaturated tetrahydropyran derivatives have received only cursory attention in the literature as heterocyclic monomers. 2,3-Dihydropyran and several of its substituted derivatives apparently undergo cationic polymerization in a manner typical of vinyl ethers (72MI11103), while tetrahydropyranyl esters of methacrylic acid (123) are fairly typical free radically polymerizable monomers (Scheme 35) (74MI11105). The THP group was used in this study as a protecting group for the acid functionality, and it was found that deprotection of polymers (124) could be accomplished under extremely mild conditions. 

A different report provided the access to a highly strained tetracyclic [3.6.6.4] ring system containing a fused tetrahydropyran-(3-lactam moiety [83]. The radical precursors 120 were easily accessible via cycloaddition reaction of the appropriate imines with a chiral chloride derived from enantiomerically pure (+)-3-carene. 

It is interesting to note that lactones 42-46, 51 corresponding to the above tetrahydropyrans 109-114 (with the exception of 125, the precursor to 115) showed a similar but attenuated trend in activities. For example, lactones 43 and 44 were most potent in this series (ethyl and propyl) at about 12 times the activity of artemisinin, and had dropped significantly in potency by butyl (45) and pentyl (46). Similarly, 3-phenylpropyl lactone 51 was reasonably potent at 4-6 times control. It is clear that removal of the lactone carbonyl in the series 108-115 provides excellent potency enhancement and that overall trends relative to lactones 42-46, 51,125 are not radically altered, but do seem to be offset somewhat (e.g. ethyl most potent in lactone series butyl most potent in tetrahydropyran series). 

Radical addition to P-alkoxyalkylidenemalonate 347 provides highly electrophilic malonyl radical intermediates 348 that undergo t>-endo cyclization onto tethered unactivated alkenes to afford tetrahydropyrans 349. The diaster-eoselectivity in the product can be improved by using bulky radicals (Scheme 84, Table 17) <2004EJ0372>. 

Table 17 Effect of increasing radical size on diastereoselec-tivity observed in tetrahydropyrans 349 (Scheme 84)...

Intramolecular cyclization of the chiral oxime ether 993 in the presence of isopropyl iodide and triethylborane affords the 3,4,5-trisubstituted tetrahydropyran-2-one 994 in poor yield but with good diastereoselectivity (Equation 388) <2003JOG5618>. Similarly, a triethylborane-induced atom transfer radical cyclization of 3-butenyl 2-iodoacetate leads to 4-(iodomethyl)tetrahydropyran-2-one. Higher yields are achieved when conducting the reaction at lower concentrations (Equation 389) <2000JA11041 >. 

Treatment of 9-oxabicyclo[3.3.1]nonan-l-ols 1014 with a combination of lead tetraacetate and copper diacetate affords 3-allenyl tetrahydropyran-2-ones 1015 via an alkoxy radical accelerated ((-fragmentation pathway (Equation 396) <2001TL2047>. 

An intramolecular acyl radical cyclization of acyl selenide 1024 uses a (Z)-vinylogous sulfonate to control rotamer population, affording ry -2,6-disubstituted tetrahydropyran-4-one 1025, a key intermediate during synthesis of the tetrahydropyran unit of mucocin (Equation 399) <1997TL5249>. This methodology is also applicable to the synthesis of polycyclic ethers <1996JOC4880>. 

The reductive lithiation of substituted tetrahydropyrans such as 82 is stereoselective, producing principally the axial organolithium at -78 °C.81 Since reductive lithiation proceeds by fast reduction of a more slowly formed radical, the stereochemical outcome of the reaction... 

The CC14 and CH2C12 radical anions223 were produced by exposing frozen solutions of carbon tetrachloride and methylene dichloride to y-radiation in the presence of tetrahydropyran. The g and hyperfine tensors obtained for these two species have axial symmetry. The fact that for CC14 Three chlorine nuclei are equivalent indicates a rapid reorientation of the radical about the C3 axis similarly, the equivalence, for CH2C12, of... 

Sulfuryl chloride, in the absence of light or free-radical initiators, acts as an electrophile. At 65-85 °C, in the dark, tetrahydrofuran and tetrahydropyran are selectively chlorinated by S02C12 to 2,3,3-trichloro tetrahydrofuran and 2,3,3-trichlorotetrahydropyran, respectively (equation 120)853,854. 

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