Mechanistic insights on the stereospecific ring opening of aziridines by carbenes a computational study

Abstract

The C-C double bond or unsaturation in organic compounds makes them biologically significant on the grounds that they are structural motifs of several natural products. In addition, the stereochemistry of organic compounds plays a major role in deciding the mode of action towards biological systems. However, the synthetic chemists face challenges to synthesize stereospecific alkenes with positive mode of action. At present, novel olefination methods have been followed to synthesize stereo-controlled olefins. Therefore, extensive study has been performed to model a part of olefin inversion to synthesize olefins through aziridine, a three-membered heterocyclic compound with different sets of carbenes as ring opening agent. A short glimpse on each chapter and their results has been listed below. Chapter 1, gives the preface of the stereospecific ring cleavage reactions, their significance and applications in the field of synthetic organic chemistry. Herein, the three membered heterocyclic compounds involved in the ring cleavages and their ring opening agents taken in the research work have been extensively discussed. In addition, the review of literature supporting the research work has been presented. Chapter 2, discusses the diverse quantum mechanical techniques used in the modeling of our chemical reactions and their elaborative theoretical background. In chapter 3, the deamination reaction of aziridine resulted in the formation of an alkene with retention of stereochemistry has been discussed. cis -2,3-dimethylaziridine undergoes ring cleavage with unsaturated carbenes to yield corresponding olefins. Ab initio and density functional investigationsof this ring opening reaction show that deamination of aziridine reaction takes place to give alkene with the same configuration. Computations suggest that the asynchronous concerted cleavage of C-N bonds leads to retention of stereochemistry. Substitution of groups at R3 and R4 of carbene carbon predict the same trend. Chapter 4, describes the ring opening reaction of cis-2,3- dimethylaziridine with methylene (a saturated carbene) to give the corresponding alkene. Density functional theory studies have been performed to study this deamination process to find out the plausible mechanism of this reaction. The investigation shows that carbene in its singlet state follows a concerted mechanism to yield alkene with the retention of stereochemistry while carbenes in the triplet state follow a stepwise mechanism which involves C-C bond rotation to give the inversion in stereochemistry. Substitutions on the methylene carbene decides the stability of the spin state of carbon and hence the mechanism of the reaction as well. newline