Tetrahydropyrans radical conformation

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... 

Rychnovsky has systematically examined 5-, 6-, 7-, and 8-membered a-oxygenated radicals as intermediates in reductive decyanations and the diastereoselectivities associated with their reactions (Scheme 18) [27]. In eaeh case, reductive decyanation with lithium in ammonia proceeds in good yield, but the selectivity varies from >20 1 in the case of the 2,6-disubstituted tetrahydropyran to 1 1 in the case of the 2,5-disubstituted tetrahydrofuran. The observed stereoselectivities in these anomeric radical reductions correlate with the conformational rigidity of the parent ring systems. 

Conformational memory is also observed in Barton radical decarboxylations of optically active tetrahydropyrans [31]. Photolysis of thiohydroxamate esters derived from optically pure tetrahydropyrans in the presence of various hydrogen atom... 

The control of anomeric stereochemistry continues to fuel the investigation into the synthetic utility of (x-oxygenated radical intermediates. Moreover, it has proven to be a valuable tool in organic synthesis, especially in the stereoselective synthesis of various substituted tetrahydropyrans, y>>n-l,3-dioxanes, and carbohydrate derivatives. The recent discovery of non-equilibrium radical reactions and conformation-induced self-regeneration of stereocenters should provide new opportunities in the ever-expanding field of a-oxygenated radical chemistry. 

The absolute configuration, i.e. S,S), of a tetrahydropyran (17) that is present in civet Viverra civetta) has been determined, using a chiral shift reagent [Eu(hfc)3] and 360 MHz n.m.r. spectroscopy in comparison with a synthetic sample of (+)-(5,5)-(17) and its methyl ester.X-Ray analysis was applied to the determination of the conformation of the violet form of cunaniol acetate (18), which was shown to have an undistorted chair form with both substituents equatorial. An e.p.r. spectral study has shown that the radical which is formed from several stereoisomeric 2,4-disubstituted tetrahydropyrans is the same, namely the cis-2-alkoxy-4-methyltetrahydropyran-2-yl radical. 

On the basis of EPR studies, Beckwith and Duggan have reported that 3-acyloxy-tetrahydropyran-2-yl radicals (4) preferentially adopt a conformation where the ester group is orientated to allow maximum overlap between the SOMO, the lone pair of the ring oxygen and the a orbital of the C—O bond. The implications of this study for the conformation of more complex glycosyl radicals are discussed. 

Another systematic study of the radical cyclization was reported by Burke and coworkers [54]. Homolytic cleavage of the carbon-selenium bond in 1.47 provided tetrahydropyran 1.49 as a single diastereomer (Scheme 1.9). The stereochemical outcome of this reaction was explained by the equatoriaUy oriented substituents, which leads to the conformational preference as shown in transition state 1.48. 

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