Mechanistic Insights into the Substrate‐Controlled Stereochemistry of Glycals in One‐Pot Rhodium‐Catalyzed Aziridination and Aziridine Ring Opening

Abstract

We carried out a principle study on the reaction mechanism of rhodium-catalyzed intramolecular aziridination and aziridine ring opening at a sugar template. A sulfamate ester group was introduced at different positions of glycal to act as a nitrene source and, moreover, to allow the study of the relative reactivity of the nitrene transfer from different sites of the glycal molecule. The structural optimization of each intermediate along the reaction pathway was extensively done by using BPW91 functional. The crucial step in the reaction is the Rh-catalyzed nitrene transfer to the double bond of the glycal. We found that the reaction could proceed in a stepwise manner, whereby the N atom initially induced a single-bond formation with C1 on the triplet surface or in a single step through intersystem crossing (ISC) of the triplet excited state of the rhodium-nitrene transition state to the singlet ground state of the aziridine complexes. The relative reactivity for the conversion of the nitrene species to the aziridine obtained from the computed potential energy surface (PES) agrees well with the reaction time gained from experimental observation. The aziridine ring opening is a spontaneous process because the energy barrier for the formation of the transition state is very small and disappears in the solution calculations. The regio- and stereoselectivity of the reaction product is controlled by the electronic property of the anomeric carbon as well as the facial preference for the nitrene insertion, and the nucleophilic addition.

A Mechanistic Study of the Stereochemical Outcomes of Rhodium‐Catalysed Styrene Aziridinations

“…[14] In addition, Perez and co-workers have identified a radical mechanism concomitant with a singlet pathway using hydrotris(pyrazolyl)-borate silver complexes, which undergo an inter-system crossing between the triplet and closed-shell singlet surfaces, accounting for the observed stereospecific aziridination of Z-alkenes. [16] In 2011, we delineated a stereoselective rhodiumcatalysed aziridination of styrene derivatives using a chiral N-tosyloxycarbamate. [16] In 2011, we delineated a stereoselective rhodiumcatalysed aziridination of styrene derivatives using a chiral N-tosyloxycarbamate.…”

“…[15] Such a pathway appears favoured with rhodium(II) catalysts as reported in the scarce DFT studies on aziridination reactions using sulfamate esters as amination reagents. [16] In 2011, we delineated a stereoselective rhodiumcatalysed aziridination of styrene derivatives using a chiral N-tosyloxycarbamate. [10d] Readily removable chiral carbamate-protected aziridines were produced in good yields and diastereoselectivities using 1 equivalent of the alkene substrate.…”

Direct Stereospecific Synthesis of Unprotected N-H and N-Me Aziridines from Olefins

“…Calculations suggest that the triplet-spin state of the nitrene ( 3 17) is more than 8 kcal/mol lower in energy than the open-shell singlet and reaction pathways identified on the triplet-spin energy surface were found to be lower in energy than reaction pathways on the singlet-spin energy surface. (39, 40) Because the Rh 2 (esp) 2 catalyst and aziridine product have singlet-spin ground states, the reaction pathway must involve spin interconversion. The mechanism outlined in Fig.…”

Mechanistic Insight into the Intramolecular Benzylic C−H Nitrene Insertion Catalyzed by Bimetallic Paddlewheel Complexes: Influence of the Metal Centers

“…The pure generalized gradient approximation (GGA) BPW91 functional was believed to appropriately discriminate the energy levels of the different electron states and was used to help keeping the calculations tractable. [11,12,21] The meta-GGAM06L functional was found to accurately predict the thermochemistry of the transition-metal-containing structures involving significant noncovalent interactions and weak interactions. [19,22] Therefore, aB PW91/6-31 + G* (SDD [23] with ECPs for the transition metals) combination was utilized in the geometry optimization and the harmonic vibrational frequency analysis.…”