Heterocyclic ambident nucleophiles. II. The alkylation of adenine

1981 ◽  
Vol 34 (5) ◽  
pp. 1107 ◽  
Author(s):  
AE Beasley ◽  
M Rasmussen
Keyword(s):  
Transition State ◽  
Alkylating Agent ◽  
Alkyl Halides ◽  
Transition State Structures

The alkylation of un-ionized adenine by a variety of primary alkyl halides under standardized, common conditions (HCONMe2, 100�) was investigated. The alkylation pattern (N 1 : N 3 : N 7 : N 9) was found to be relatively insensitive to changes in the nature of the alkylating agent, except for cases involving benzyl chloromethyl ether and chloromethyl pivalate. An interpretation of these patterns in terms of modern ambient nucleophile reactivity concepts and variable SN2 transition state structures is presented.

Alkylation of camphor imines of glycinates. Diastereoselectivity as a function of electronic factors in the alkylating agent

1986 ◽  
Vol 64 (4) ◽  
pp. 726-731 ◽  
Author(s):  
John M. McIntosh ◽  
Pratibha Mishra
Keyword(s):  
Transition State ◽  
Alkylating Agent ◽  
Alkylating Agents ◽  
Type Systems ◽  
Alkyl Halides ◽  
State Interaction ◽  
Tert Butyl ◽  
Ca 50

Alkylation of the (R)-camphor imine of tert-butyl glycinate with a variety of alkylating agents gave diastereoselectivities ranging from 0–100%. Simple alkyl halides larger than methyl give de's (diastereomeric excesses) of ca. 50% whereas those derived from allylic type systems afford de's of 75–100%. The results are best explained by invoking a transition state interaction between the π system of the alkylating agent and the imine which, for steric reasons, requires alkylation to occur from the pro-R face.

Heterocyclic Ambident Nucleophiles. V. Alkylation of Benzimidazoles

1993 ◽  
Vol 46 (8) ◽  
pp. 1177 ◽  
Author(s):  
JR Howell ◽  
M Rasmussen
Keyword(s):  
Transition State ◽  
Electrostatic Field ◽  
Alkyl Halides ◽  
Proximity Effects ◽  
Aprotic Solvents ◽  
Control Factors ◽  
Transition State Structures

Alkylation of 5-substituted benzimidazole anions with a variety of primary alkyl halides in both protic and aprotic solvents showed only small regioselectivity , with a slight preference for reaction at N1 for 5-nitro and N3 for 5-methoxy systems. With 4-substituted benzimidazole anions, alkylation gave more divergent results with the N1 to N3 regioselectivity varying between 100:0 and 29:71. These alkylation patterns are interpreted as deriving from an interplay of electrostatic, thermodynamic, steric and associative control factors within the variable SN2 transition state structures involved. In the 4-substituted series, proximity effects, both electrostatic field and steric non-bonded, are clearly dominant.

scholarly journals Popular Integration Grids Can Result in Large Errors in DFT-Computed Free Energies

2019 ◽  
Author(s):  
Andrea N. Bootsma ◽  
Steven Wheeler
Keyword(s):  
Transition State ◽  
Molecular Orientation ◽  
Density Functional ◽  
Basis Sets ◽  
Free Energies ◽  
Functional Theory ◽  
Metal Free ◽  
Stereoselective Reactions ◽  
Functionalization Reaction ◽  
Transition State Structures

<div>Density functional theory (DFT) has emerged as a powerful tool for analyzing organic and organometallic systems and proved remarkably accurate in computing the small free energy differences that underpin many chemical phenomena (e.g. regio- and stereoselective reactions). We show that the lack of rotational invariance of popular DFT integration grids reveals large uncertainties in computed free energies for isomerizations, torsional barriers, and regio- and stereoselective reactions. The result is that predictions based on DFT-computed free energies for many systems can change qualitatively depending on molecular orientation. For example, for a metal-free propargylation of benzaldehyde, predicted enantioselectivities based on B97-D/def2-TZVP free energies using the popular (75,302) integration grid can vary from 62:38 to 99:1 by simply rotating the transition state structures. Relative free energies for the regiocontrolling transition state structures for an Ir-catalyzed C–H functionalization reaction computed using M06/6-31G(d,p)/LANL2DZ and the same grid can vary by more than 5 kcal mol–1, resulting in predicted regioselectivities that range anywhere from 14:86 to >99:1. Errors of these magnitudes occur for different functionals and basis sets, are widespread among modern applications of DFT, and can be reduced by using much denser integration grids than commonly employed.</div>

Evaluating transition state structures of vanadium–phosphatase protein complexes using shape analysis

2015 ◽  
Vol 147 ◽  
pp. 153-164 ◽  
Author(s):  
Irma Sánchez-Lombardo ◽  
Santiago Alvarez ◽  
Craig C. McLauchlan ◽  
Debbie C. Crans
Keyword(s):  
Transition State ◽  
Shape Analysis ◽  
Protein Complexes ◽  
Transition State Structures
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