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On the Effect of Tether Composition on cis / trans Selectivity in Intramolecular Diels–Alder Reactions
Author(s) -
PaddonRow Michael N.,
Longshaw Alistair I.,
Willis Anthony C.,
Sherburn Michael S.
Publication year - 2009
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.200800352
Subject(s) - intramolecular force , selectivity , chemistry , diels–alder reaction , composition (language) , stereochemistry , organic chemistry , catalysis , art , literature
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, H 2 CCHCHCHCH 2 XZCHCH 2 [XZ=CH 2 CH 2 ( 1 ); OC(O) ( 2 ); CH 2 C(O) ( 3 ); OCH 2 ( 4 ); NHC(O) ( 5 ); SC(O) ( 6 ); OC(S) ( 7 ); NHC(S) ( 8 ); SC(S) ( 9 )]. For each system studied ( 1 – 9 ), cis ‐ and trans ‐TS isomers, corresponding, respectively, to endo ‐ and exo ‐positioning of the CXZ tether with respect to the diene, have been located and their relative energies ( E rel TS ) employed to predict the cis / trans IMDA product ratio. Although the E rel TS values are modest (typically <3 kJ mol −1 ), they follow a clear and systematic trend. Specifically, as the electronegativity of the tether group X is reduced (XO→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 C4C5 bond, that is caused by the CXC(Y) group’s strong tendency to maintain local planarity; and (2) attractive electrostatic and secondary orbital interactions between the endo ‐(thio)carbonyl group, CY, and the diene. The former interaction predominates when X is weakly electronegative (XN, S), while the latter is dominant when X is more strongly electronegative (XO), or a methylene group (XCH 2 ) 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 .