Computational Organic Chemistry: Bridging Theory and Experiment in Establishing the Mechanisms of Chemical Reactions

Abstract

Understanding the mechanisms of chemical reactions, especially catalysis, has been an important and active area of computational organic chemistry, and close collaborations between experimentalists and theorists represent a growing trend. This Perspective provides examples of such productive collaborations. The understanding of various reaction mechanisms and the insight gained from these studies are emphasized. The applications of various experimental techniques in elucidation of reaction details as well as the development of various computational techniques to meet the demand of emerging synthetic methods, e.g., C-H activation, organocatalysis, and single electron transfer, are presented along with some conventional developments of mechanistic aspects. Examples of applications are selected to demonstrate the advantages and limitations of these techniques. Some challenges in the mechanistic studies and predictions of reactions are also analyzed.

Elusive Reaction Intermediates in Solution Explored by ESI‐MS: Reverse Periscope for Mechanistic Investigations

“…[8] Thepotential of this technique can be complemented and increased by MS n (n:m ultiple steps of product ion analysis) performance,ion mobility,ion spectroscopy, [9] and computational studies. [10,11] Herein we aim to review the most relevant and recent contributions on mechanistic studies of organic reactions, studies carried out by intercepting intermediates with ESI-MS.W ew ill also address the reliability of the various methods,a sw ell as their use in combination with the abovementioned techniques.…”

Computational and Synthetic Investigation of Cationic Rearrangement in the Putative Biosynthesis of Justicane Triterpenoids

“…We planned to elucidate the mechanism of this rearrangement by synthetic, computational, [16] and kinetic investigations. It was thus necessary to access a justicioside A-type rearrangement precursor and examine the migration to justicioside E aglycone ( 1 ).…”

Highly Regio‐ and Stereoselective Hydrosilylation of Internal Thioalkynes under Mild Conditions

“…(1); TBAF = tetrabutylammonium fluoride].T he oxidation of 3k with m-chloroperbenzoic acid (mCPBA) afforded the stereodefined a-silyl vinyl sulfone 4 with high efficiency. [11] Them echanism involves the direct formation of ar uthenacyclopropene intermediate, followed by silyl migration; [12] in this process the hydrogen atom and the silyl group of the silane are arranged on opposite sides of the ruthenacyclopropene plane. [9] Furthermore,p rotodesilylation and Hiyama cross-coupling efficiently furnished vinyl sulfides 5 and 6,r espectively.O ur method provides an attractive alternative route to these molecules.…”

“…[11] Them echanism involves the direct formation of ar uthenacyclopropene intermediate, followed by silyl migration; [12] in this process the hydrogen atom and the silyl group of the silane are arranged on opposite sides of the ruthenacyclopropene plane. [15] Also,the ruthenacyclopropene intermediate 2Ais more stable than 2B by 5.2 kcal mol À1 because the proton-like hydrogen atom [11] preferentially attacks the more electron-rich C b atom with the strongly p donating sulfenyl group.M oreover,t he sulfenyl group stabilizes the electrophilic carbene ligand in 2A through ac onjugation effect (see resonance structure 2A 1 , Figure 1; see also Figure S2 a). [14] Interestingly,t he presence of as ulfenyl substituent leads to a selectivity and the unusual syn addition.…”