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In contrast to the simple 4,4′-bi-1,3-dioxanyl derivative 6, which has no conformational preference at the inter-ring bond, the derivatives 9 and 10, which have two strategically placed axial methyl groups, show conformational preferences exceeding 95 %. This is related to the conformational preference found in one of the substructures of the natural product prymnesin. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

A convergent synthesis of the meso-ter(1,3-dioxanyls) 8−11 has been achieved, starting from two enantiomeric building blocks in each case. The stereogenic centres in the central linkage region were set up by stereocontrolled aldol additions. Structure assignment of the final products was based on comparisons between experimental and calculated 3JH,H coupling constants, which reflect distinct conformer populations. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Stereoselective synthesis of a series of 1,3-dioxan-4-ylmethanes 1−9 has been achieved by use of solely substrate-based asymmetric induction. The simple C2-symmetric bis(dioxanyl)methane 1 has a greater than 99% conformational preference at the two inter-ring bonds for the conformation 1a. The homologous structures 3−9 contain up to five dioxanylmethane units, maintaining a high conformational preference in each of the bis(dioxanyl)methane units. Thus, these flexible compounds reach a conformational preference in excess of 90% over up to eight rotatable inter-ring bonds. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Compounds 12−15, meso-type 2,3,4,5,6,7-hexasubstituted octane derivatives, have been synthesized using solely substrate-based asymmetric induction. Thanks to the specific relative configurations at the six stereogenic centres, these compounds have a high tendency to populate the conformation with a fully extended zig-zag backbone chain.

A 2,4-dimethylpentane unit can be rendered monoconformational by the presence of a conformation-inducing group (an inductor group) at C-1 (cf. 6). The resulting entity may serve as an inductor group to control in turn the conformation of a neighboring dimethylpentane segment (cf. 7). This holds if the inducing dimethylpentane segment is isotactic (cf. 15, 25), but not when it is syndiotactic (cf. 28).

An isobutyl group placed equatorially in the 2-position of a 1-equatorially substituted cyclohexane adopts a preferred conformation (cf. 5). This also holds when it is placed in the 2-position on a 3-equatorially substituted tetrahydropyran (cf. 6). The same conformational preference is found for 2-methoxypropyl residues in the 2-position of 3-substituted tetrahydropyrans (cf. 8 and 10). The latter compounds chelate lithium cations as analogues of 1,2-dimethoxyethane. Through this complexation, it is possible to effect a change in the side chain conformation.

2,4-Disubstituted pentanes are molecules which adopt essentially only two conformations. Substituents have been varied in order to find those which lead to a strong preference of the conformer equilibrium. Studying 2-substituted 4-methylpentanes 3 and 4-benzyloxypentanes 12, it has been shown that substituent effects on the conformer equilibria are not additive, as would be expected on the grounds of steric effects alone. Rather, interactions between polar groups reinforce the bias of the conformer equilibria. When applied to 2,4-disubstituted pentanes, substituents such as chloro or phthalimido shift the conformer equilibrium to the side of the gg conformer with preferences exceeding 90%.

Whereas simple 4,4′-bi(1,3-dioxanyl)s 16 and 19 displayed little conformational preference at the inter-ring bond, their derivatives 4 and 13, with equatorial methyl groups in the 5- and 5′-positions, each showed a strong conformational preference to populate a conformation with a gauche arrangement of the oxygen atoms. These results form the basis of a modular approach to oligo-1,3-dioxanyls 5, 6, and 29, in each of which a strong conformational preference prevails at all of the inter-ring bonds. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)