Anatoly M. Belostotskii

Conformational Schemes: An Available Tool for the Assignment of NMR-Measured Barriers, Demonstrated with the Example of Crowded Piperidines

MM3-Derived conformational schemes for systems with complex conformational dynamics, such as the substituted piperidine depicted here, permit the assignment of NMR-measured barriers to the corresponding processes.

A simple method of preparation of 7-alkyl-7-azabicyclo[2.2.1]heptanes

Abstract Action of triphenylphosphine - carbon tetrachloride on the trans-4-alkylaminocyclohexanols leads to 7-alkyl-7-azabicyclo[2.2.1]heptanes in the good yields. The starting aminoalcohols are easily available from the monoethylene ketal of 1,4-cyclohexanedione and primary amines in a four step process without isolation of intermediates.

Intramolecular dynamics in 4- to 6-membered saturated azacycles: a MM3 study☆

Abstract We show that the MM3 force field provides a reasonable modeling of the transition states of dynamic processes related to ring inversion for azetidines, pyrrolidines and piperidines. These involve isolated ring inversion (RI) and concerted ring inversion-nitrogen inversion-CN rotation (RINIR). Pseudorotation and concerted pseudorotation-nitrogen inversion are additional processes for piperidines. The schemes of conformational transformations (including a relationship of conformers with corresponding transition states) were established for these amines using a normal mode vibrational analysis. Pyramidal nitrogen inversion was found to occur only as the RINIR process for azetidine and pyrrolidine compounds, while nitrogen inversion as well as RINIR are inherent to NMe piperidine. Only the C s mode was attributed to interconversion of the piperidine ring (differing from the known cyclohexane case). The designed conformational schemes allowed the reassignment of the previously measured barriers (NMR) for these cyclic amines.

MM3 force field as a tool in mechanistic studies of nitrogen inversion processes for alkylamines

Abstract We show that the MM3 force field provides a reasonable modelling of the transition state of nitrogen inversion-rotation (NIR) for alkylamines and thus a quantitative estimate of nitrogen inversion barriers for amines of different structures. In general, the NIR barriers for most open-chain, monocyclic and polycyclic amines are now available within 0.7 kcal mol−1 (standard deviation) of the experimental values. However, for isopropyl- or isobutyl-type amines and pyrrolidine compounds this correlation between the calculated and experimental barriers drops down to 2.7 kcal mol−1. An effective study of the mechanism of the NIR process, and thus the assignment of NMR-measured barriers, proved possible using MM3-calculated barriers for the isolated rotation (ISR), as well as the concerted NIR. A simple MM3-based test was developed to identify the amines for which an NIR process excludes an isolated rotation process.

Crowded Piperidines with Intramolecularly Hydrogen-Bonded Nitrogen: Synthesis and Conformation Study

2,2,6,6-Tetramethyl substituted piperidines with a beta-branched N-alkyl substituent were synthesized by the photoreaction of N-Me precursors with ketones. The main conformation features of these sterically-hindered amines (established by NMR and IR spectroscopy) are a ring in the chair form, an eclipsed conformation for the N-substituent and an intramolecular OH...N bond. High barriers for the geminal substituent topomerization were measured for these piperidines at different temperatures by means of line-shape analysis of the temperature-dependent 13C and 1H NMR spectra. An MM3-derived conformation scheme indicated that, for one of the studied analogues, the rotation of the N-substituent determines a slow topomerization rate. A new mechanism of nitrogen inversion--a concerted hydrogen-bond dissociation/nitrogen inversion process--is considered for hydrogen-bonded amines.

Conformational Preferences for 3‐Piperideines: An Ab Initio and Molecular Mechanics Study

Conformational preferences in alkyl- as well as Ph-substituted 3-piperideines (1,2,3,6-tetrahydropyridines) have been characterized by ab initio and molecular mechanics calculations. A set of rules and subrules for estimation of the conformational equilibrium (in terms of preferred substituent orientation) in these systems. with differently positioned ring substituent (-s), is presented. Examples of the revision of some previous stereochemical assignments demonstrate the reliability of these rules.

New nucleoside heteroanalogues: Desoxynucleoside selenocyanates

Abstract New nucleoside heteroanalogues, 5′- and 3′-desoxynucleoside selenocyanates and primary desoxysugar selenocyanates, were synthesized from activated nucleoside and sugar derivatives and a new convenient seleno nucleophile, tetrabutylammonium selenocyanate. Tresylate-based activation of hydroxy functions turned out to be most successful for formation of these selenocyanates compared with mesylate- or triflate-based activation.

On Li-chelating additives to electrolytes for Li batteries

The relative affinity of several electrochemically stable bi- and polydentate organic ligands (containing ether, amino, carbonate or phosphonate moieties) to Li ion was estimated by ab initio calculations at the MP2/6-31G(d) level comparing their calculated binding energies (BEs). Polyether 12-crown-4 and a bisphosphonate, which is covalently locked in a cyclic “chelating” conformation, are stronger Li+ chelators than isosparteine and 1,2-methylenebisphosphonate (an open-chain compound). Organic biscarbonates are the weakest complexing agents among the ligands considered. Although BE values were calculated for the gas phase, the order of ligand complexation ability obtained is also considered relevant to solutions since the difference between the BEs for these three groups of ligands is significant. The same calculations that were performed for complexes of Li ion and different organic carbonate diesters (solvents usually used in Li-ion batteries) allowed singling out of conformationally locked bisphosphonates as new battery life-prolonging additives to carbonate electrolytes.

NEW 3′-DEOXYTHYMIDINES BEARING A NUCLEOPHILIC 3′-SUBSTITUENT

New potential cancer-driven as well as HIV-driven nucleoside hetero- analogs, such as 3′-thio- and 3′- as well as 5′-selenosubstituted thymidines, have been synthesized. We also report an effective method for the preparation of novel nucleoside derivatives, bis(deoxynucleoside) diselenides, in nearly quantitative yields. The North conformation is significantly populated in the conformational equilibrium for 3′-α-alkylthiothymidines.

Etherification of hydroxysteroids via triflates

Abstract Triflates of saturated alcohols are useful in the alkylation of 3- and 17-hydroxysteroids in the presence of hindered amines. The etherification is successful even in those cases where other alkylating agents are noneffective.