TY - JOUR
T1 - On the effect of tether composition on cisltrans selectivity in intramolecular diels-alder reactions
AU - Paddon-Row, Michael N.
AU - Longshaw, Alistair I.
AU - Willis, Anthony C.
AU - Sherburn, Michael S.
PY - 2009/1/5
Y1 - 2009/1/5
N2 - 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.
AB - 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.
KW - Cycloaddition
KW - Density functional calculations
KW - Diastereoselectivity
KW - Tether groups
KW - Transition structures
UR - http://www.scopus.com/inward/record.url?scp=58149178730&partnerID=8YFLogxK
U2 - 10.1002/asia.200800352
DO - 10.1002/asia.200800352
M3 - Article
SN - 1861-4728
VL - 4
SP - 126
EP - 134
JO - Chemistry - An Asian Journal
JF - Chemistry - An Asian Journal
IS - 1
ER -