Diels–Alder Reactions of Symmetrically 1,4‐Disubstituted Dienes: Theoretical Study on the Influence of the Configuration of the Double Bonds on the Regio‐ and Endoselectivity

Abstract

It was experimentally shown in Diels‐Alder reactions that symmetrically 1,4‐disubstituted dienes exhibit high regio‐ and endoselectivity induced by the (E,Z) configuration of the double bonds. In order to understand the origin of this selectivity, the transition states associated with the reaction between a series of such dienes (R = OMe, CH3, NH2, F, CN) on substituted ethylene (R′ = CO2Me, CN, F, OMe) were determined by DFT calculations. If the regioselectivity confirmed by a single‐point MP2 calculation is predicted to be good in most cases, its direction remains difficult to predict; the R′ group of the dienophile can orient itself toward either the (Z) or the (E) side of the diene. Neither primary nor secondary frontier orbital interactions appear to be able to rationalize these results. They are more likely explained by a delicate balance between steric and electrostatic interactions. This hypothesis is further supported by the calculated reactivity of the (E,E) and (Z,Z) corresponding dienes. In any case, a standard DFT calculation, confirmed by a single‐point MP2 step, is likely to provide a reliable guideline for a synthesis strategy that allows the control of up to four stereogenic centres in a single reaction step.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Theoretical Study on Hetero‐Diels–Alder Reaction of Butadiene with Benzaldehyde Catalyzed by Chiral InIII Complexes

“…In terms of ligand, the Jørgensen group [15] employed the chiral 1,1Ј-binaphthol (BINOL) ligand and the Yamada group [19] adopted the salen ligand. They also performed theoretical studies on HDA reactions catalyzed by metal (aluminum and cobalt, respectively) complexes.…”

“…Recently, the Chaquin group [19] investigated the influence of the configuration of the double bond on the regio-and endo-selectivity in DielsAlder reactions. The origin of the selectivities was attributed to the balance between steric hindrance and electrostatic interaction.…”

Reaction mechanisms : Part (ii) Pericyclic reactions

“…Chaquin and coworkers used B3LYP and MP2 calculations to probe the regio-and endo-selectivity of the Diels-Alder reactions of 1,4-disubstituted dienes with monosubstituted alkenes (Scheme 1). 5 The authors found that the orientation of the Y group of the alkene in such systems is difficult to predict; this feature appears to be controlled by a ''delicate balance between steric and electrostatic interactions.'' Houk and co-workers described calculations (B3LYP, CASPT2, CBS-QB3) on the dimerization of 1,3-cyclohexadiene (Scheme 2).…”

“…Peles and Thoburn reexamined the [1,5] shift in (Z)-1,3-pentadiene (Scheme 41) using mPW1K/6-31+G(d,p) calculations. 48 Rates, kinetic isotope effects and Swain-Schaad exponents were calculated for various isotopologues, and it was concluded that ''multidimensional tunneling is needed to account for the experimental KIEs''.…”

“…Bergman and coworkers examined the mechanism of the S N 2 0 reaction shown in Scheme 47, providing computational evidence (B3LYP/LANL2DZ) that it is best described as a concerted but asynchronous [3,3] sigmatropic shift. 53 Other sigmatropic shifts Nouri and Tantillo described B3LYP/6-31G(d) calculations on a series of [4,5] sigmatropic shifts for cycloalkanes bearing diene and allyl substituents (Scheme 48). 54 These authors concluded that such rearrangements, some of which lead directly to orbital symmetry ''forbidden'' products, are only formally pericyclic, even in cases where they are concerted, since their bond-making and bond-breaking events occur quite asynchronously.…”