Open chain compounds with preferred conformations1

Göttlich, Richard; Kahrs, B. Colin; Krüger, Joachim; Hoffmann, Reinhard W.

doi:10.1039/a603040h

Cited by 43 publications

(28 citation statements)

References 22 publications

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“…If this conformer is populated to b 80 %, we call the compound or a particular segment of a compound monoconformational. [6,7] As a first step, we want to identify small segments of a hydrocarbon backbone, segments that, by virtue of their substituent pattern, have only a single low-energy conformation. As a next step we shall consider how these segments may be connected with one another to result in larger hydrocarbon backbones, which should ideally maintain the property of preferentially populating a single conformation.…”

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confidence: 99%

Conformation Design of Hydrocarbon Backbones: A Modular Approach

et al. 1998

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IntroductionUnbranched hydrocarbon chains have an enormous number of populated low-energy conformers. [2, 3] This number can be reduced by substituents that introduce steric strain in certain conformers. This is achieved most effectively [4] if these substituents create destabilizing syn-pentane interactions, [5] which add 7 ± 9 kJ mol À1 to the energy of a given conformer. The population of the remaining low-energy conformers is thereby increased (see Scheme 1).We are interested in defining substitution patterns on a hydrocarbon chain that would thus destabilize all but one conformer, which would remain free of syn-pentane inter- actions. This conformer would then be the only low-energy conformer and should be highly preferentially populated. If this conformer is populated to b 80 %, we call the compound or a particular segment of a compound monoconformational. [6,7] As a first step, we want to identify small segments of a hydrocarbon backbone, segments that, by virtue of their substituent pattern, have only a single low-energy conformation. As a next step we shall consider how these segments may be connected with one another to result in larger hydrocarbon backbones, which should ideally maintain the property of preferentially populating a single conformation. Discussion 1. Basic types of monoconformational skeletons: The smallest hydrocarbon segment to be considered is 2,3-dimethylbutane (2).[8] When rotating about the central 2,3-bond, 2 has three rotamers that are located at energy minima, 2 a ± c (Scheme 2). Rotamer 2 c is the lowest energy conformer. Energies of 2 a and 2 b are calculated to be slightly (ca. 1.5 kJ mol À1 ) higher, because one of the methyl groups is exposed to a double gauche interaction with two other methyl groups. To render the 2,3-dimethylbutane backbone monoconformational, two out of the three conformations of 2 have to be destabilized selectively, for example by introducing syn-pentane interactions. For instance, if it were possible to place an additional methyl group at C1 of 2, with the methyl group kept in an antiperiplanar orientation to the neighboring C2 methyl group, that is, 3, syn-pentane interactions would be created in conformers 3 b and 3 c, but not in 3 a. Likewise, if it were possible to fix the additional methyl group at C1 of 2 in a Conformation Design of Hydrocarbon Backbones: A Modular Approach** Reinhard W. Hoffmann,* Martin Stahl, Ulrich Schopfer, and Gernot Frenking* Abstract: A modular approach towards a conformation design of hydrocarbon backbones is described. The idea is to attach substituents (e.g., methyl branches) to a hydrocarbon backbone in such a manner that they create destabilizing syn-pentane interactions in all but one diamond-lattice backbone conformation. This creates a substantial (b 7 kJ mol À1 ) energy gap between the lowest energy conformer and the higher energy conformers. In consequence, the lowest energy conformer will be populated to a high extent (e.g., b 80 %). Small hydrocarbon modules that fulfil this requirement have been identified...

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Conformation Design of Hydrocarbon Backbones: A Modular Approach

et al. 1998

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“…Diastereoselectivity increases for the all-syn deoxypropionate upon addition of subsequent methyl substituents (Scheme 12). This increased selectivity was also observed in the synthesis of mycocerosic and phthioceranic acid (vide infra) and is probably the result of a distinct conformation in the transition-state in which 1,5-syn-pentane interactions 31 are minimized or avoided as was also observed by Hanessian. elucidated its absolute stereochemistry by degradation studies, confirmed subsequently by the synthesis of mycocerosic acid starting from chiral pool compounds and via a route involving kinetic resolution.…”

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confidence: 52%

Iterative strategies for the synthesis of deoxypropionates

2010

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“…The data for 4 in Table 1 show an extreme variation in the values of the coupling constants J 2-H/3-H and J 3-H/4-H (1.4 and 12.2 Hz), as would be expected [23] for the prevalence of a single preferred conformation. This preferred conformation (cf.…”

Section: Conformational Analysismentioning

confidence: 95%

Synthesis and Conformational Analysis of Bis(1,3‐dioxan‐5‐yl)ethane Derivatives

Hoffmann

Menzel

Harms

2002

European J Organic Chem

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Bis(1,3-dioxan-5-yl)ethanes 4, 30, 32, and 33 were synthesized in order to verify the high conformational preferences of their flexible backbones predicted by force-field calculations. Conformational analysis based on 3 J H,H coupling constants gave results different from expectations based on the force-field calculations. The MM3* force-field of MACROMany of the natural products of polyketide biogenetic origin have conformational preferences, be it global ones or local ones in certain segments of the molecule. [2] This is assumed to be the result of an evolutionary process, optimizing the binding properties of these molecules to their corresponding receptors. Over the last few years we have been interested in learning how conformational preferences are attained in the flexible open-chain structures used by nature. We are interested in identifying principles that might be applicable in the design of flexible molecules with preferred conformations, molecules not necessarily patterned after the polypropionate structures found in nature. [3] A general search identified some substituent patterns for alkane chains that should give rise to preferred backbone conformations. [4] One such substituent pattern is shown in 1, for which a conformation with an extended chain should be favored, because all the other (undesired) conformations are of higher energy. [4,5] Rotation about the C-2/C-3 bond in 1 generates conformations with a syn-pentane interaction. These conformers relax to a non-diamond lattice conformation, calculated to be ϩ1.6 and ϩ2.0 kcal·mol Ϫ1 higher in energy than conformation 1a. [5] Similarly, rotation about the central C-3/C-4 bond generates conformations ϩ2.6 kcal·mol Ϫ1 higher in energy than 1a. Because there are three rotatable bonds, the overall conformation preference for 1 is calculated to be only 80%.[ ‡] Flexible Molecules with Defined Shape, XVIII. Part XVII:MODEL was apparently not parametrized suitably to deal with the double-gauche interactions occurring along the backbones of compounds 30, 32, and 33.

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Open chain compounds with preferred conformations1

Cited by 43 publications

References 22 publications

Conformation Design of Hydrocarbon Backbones: A Modular Approach

Conformation Design of Hydrocarbon Backbones: A Modular Approach

Iterative strategies for the synthesis of deoxypropionates

Synthesis and Conformational Analysis of Bis(1,3‐dioxan‐5‐yl)ethane Derivatives

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