Tetrahydropyran ring strain

The X-ray crystallographic analysis of thyrsiferol 18-acetate (5) revealed a strained tetrahydropyran ring C in a twist-boat conformation so as to avoid 1,3-diaxial interactions between the methyl groups at Cio and Cl 5. Initial biological studies of the natural product by Munro et al did not reveal any significant pharmacological activity [4]. 

Consequently, due to the ability to attain the favorable conformation, the ring strain for the 6-membered cyclic ether (tetrahydropyrane) is lower than that for the 5-membered one (THF). The same is true for cyclic acetals. 

It is interesting to compare the ease of conversion of deodarone to atlantone with the reverse conversion. The explanation lies in the greater stability of atlantone. In this molecule, there is considerable resonance stabilisation because of the delocalisation possible in the unsaturated ketone. Furthermore, there is some steric strain in deodarone which is relieved when the tetrahydropyran ring is opened. 

From the structures of these compounds, it is apparent that the ease of polymerization is related to the degree of ring strain. Ethylene oxide is a highly strained three-membered ring. The need to release this strain provides the driving force for polymerization and is reflected in the ease with which ethylene oxide undergoes polymerization. The ring strain decreases in the flve-membered tetrahydrofuran and is absent in the six-membered tetrahydropyran. 

Hashimoto, M., Kan, T, Yanagiya, M., Shirahama, H., and Matsumoto, T. (1987) Synthesis of A-B-C-ring segment of thyrsiferol constmction of a strained tetrahydropyran ring existent as a boat form. Tetrahedron Lett., 28, 5665-5668. 

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. 

Tetrahydropyranes and tetrahydrofuranes, with their low strain energies will tend to retain the ring more in the initial products. For example, a tetrahydrofuranyl radical will form an unsaturated ring compound in reacting with O2 although homolysis to give unsaturated aldehydes will also be competitive. 

Copolymerization was carried out in C2H5C1 solvent at 0 °C and at 40 mol % total comonomer concentration with a A1(C2H5)3-H20 catalyst system 13). Under these conditions, depropagation of THF and tetrahydropyran (THP) should be taken into account, and thus r, and r2 derived from Scheme (15-1) cannot be equal for these monomers to the corresponding rate constant ratios (reactivity ratios). Therefore, only results for oxiranes and oxetanes can be discussed. It should be noted that in spite of the higher strain of the three-membered rings, their incorporation into the copolymer is slower than that of the more basic oxetanes. 

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