Origins of the Regioselectivities in the Diels−Alder Reactions of Vinylindenes with 1,4-Quinone Monoketal and Acrolein Dienophiles

Abstract

Computations with density functional theory (B3LYP/6-31G(d)) have elucidated the origins of regioselectivities in the Diels-Alder reaction of vinylindene with a 1,4-quinone monoketal reaction that was employed as the key step in the synthesis of fluostatin C. Frontier Molecular Orbital theory and an electrostatic model are applied to the reactions of alkyl-substituted and vinylindene dienes with 1,4-quinone monoketal and acrolein dienophiles. Regiochemical results that deviate from expectation are explained by a progression from electronic to steric control upon the addition of a Lewis acid catalyst.

Origins of Stereoselectivity in the trans Diels−Alder Paradigm

“…Radical species were optimized with unrestricted (UB3LYP) density functional calculations. We have shown previously that this level of electronic structure theory is capable of providing ground-state and transition-state geometries for organic radicals that agree well with more elaborate calculations, and that the results obtained agree quantitatively with experiment 26. We have also performed single point energy calculations with M06-2X/UM06-2X density functional theory (DFT)27 that are expected to deliver a more accurate treatment of medium-range correlation effects, such as van der Waals interactions.…”

Revealing the Origin of Π‐facial and Regioselectivity in the Diels‐Alder Reaction of Unsymmetrical, Cage‐annulated 1,3‐Cyclohexadiene with Ethyl Propiolate Dienophile: a DFT Study

“…The molecular electrostatic potential is used to predict the probable sites of molecules for [4+2] cycloaddition in intramolecular Diels‐Alder reaction [32,33] The MESP study of the caged dienes HPDD and HHDD was carried out at the M06‐2X/6‐31+G(d,p) level of theory to elucidate the π‐facial differentiation of these dienes [32,34] . The MESP surfaces of HPDD and HHDD are shown in Figure 1.…”

A DFT investigation of Diels-Alder reaction of ethyl propiolate to the cage-annulated hexacyclo[7.5.2.01,6.06,13.08,12.010,14]hexadeca-2,4-diene-7,16-dione

“…The molecular electrostatic potential (MEP) map is widely used to identify the most probable site of molecules for cycloaddition in intermolecular DA reactions. 30,31 The red on the map indicates the negative region pertaining to electrostatic potential, representing the region with a high electron density on the entire molecule, which is hence prone to cycloaddition. The blue indicates the region with partially positive charges, and this site is unfavorable for cycloaddition.…”