On the effect of tether composition on cisltrans selectivity in intramolecular diels-alder reactions

Michael N. Paddon-Row, Alistair I. Longshaw, Anthony C. Willis, Michael S. Sherburn

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    14 Citations (Scopus)

    Abstract

    Intramolecular Diels-Alder (IMDA) transition structures (TSs) and energies have been computed at the B3LYP/6-31+G(d) and CBS-QB3 levels of theory for a series of 1,3,8-nonatrienes, H2C=CH-CH=CH-CH2X-Z-CH= CH2 [-X-Z-=-CH2-CH2(1); -O-C(=O)- (2); -CH 2-C(=O)-(3); -O-CH2- (4); -NH-C(=O)- (5); -S-C(=O)- (6); -O-C(=S)- (7); -NH-C(=S)- (8); -S-C(=S)- (9)]. For each system studied (1-9), cis- and trans-TS isomers, corresponding, respectively, to endo- and exo-positioning of the -C-X-Z- tether with respect to the diene, have been located and their relative energies (ErelTS) employed to predict the cis/trans IMDA product ratio. Although the Erel TS values are modest (typically <3kJmol-1), they follow a clear and systematic trend. Specifically, as the electronegativity of the tether group X is reduced (X=O-→ NH or S), the IMDA cis stereoselectivity diminishes. The predicted stereochemical reaction preferences are explained in terms of two opposing effects operating in the cis-TS, namely (1) unfavorable torsional (eclipsing) strain about the C4-C5 bond, that is caused by the -C-X-Q=Y)- group's strong tendency to maintain local planarity; and (2) attractive electrostatic and secondary orbital interactions between the ertdo(thio)carbonyl group, C=Y, and the diene. The former interaction predominates when X is weakly electronegative (X=N, S), while the latter is dominant when X is more strongly electronegative (X=O), or a methylene group (X=CH2) which increases tether flexibility. These predictions hold up to experimental scrutiny, with synthetic IMDA reactions of 1, 2, 3, and 4 (published work) and 5, 6, and 8 (this work) delivering ratios close to those calculated. The reactions of thiolacrylate 5 and thioamide 8 represent the first examples of IMDA reactions with tethers of these types. Our results point to strategies for designing tethers, which lead to improved cis/trans-selectivities in IMDAs that are normally only weakly selective. Experimental verification of the validity of this claim comes in the form of fumaramide 14, which undergoes a more trans-selective IMDA reaction than the corresponding ester tethered precursor 13.

    Original languageEnglish
    Pages (from-to)126-134
    Number of pages9
    JournalChemistry - An Asian Journal
    Volume4
    Issue number1
    DOIs
    Publication statusPublished - 5 Jan 2009

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