Ferrocenoyl-adenines: substituent effects on regioselective acylation
A series of N 6 -substituted adenine–ferrocene conjugates was prepared and the reaction mechanism underlying the synthesis was explored. The S N 2-like reaction between ferrocenoyl chloride and adenine anions is a regioselective process in which the product ratio ( N 7/ N 9-ferrocenoyl isomers) is g...
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Veröffentlicht in: | Beilstein journal of organic chemistry 2022-09, Vol.18 (1), p.1270-1277 |
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Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
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Zusammenfassung: | A series of
N
6
-substituted adenine–ferrocene conjugates was prepared and the reaction mechanism underlying the synthesis was explored. The S
N
2-like reaction between ferrocenoyl chloride and adenine anions is a regioselective process in which the product ratio (
N
7/
N
9-ferrocenoyl isomers) is governed by the steric property of the substituent at the
N
6
-position. Steric effects were evaluated by using Charton (empirical) and Sterimol (computational) parameters. The bulky substituents may shield the proximal
N
7 region of space, which prevents the approach of an electrophile towards the
N
7 atom. As a consequence, the formation of
N
7-isomer is a kinetically less feasible process, i.e., the corresponding transition state structure increases in relative energy (compared to the formation of the
N
9-isomer). In cases where the steric hindrance is negligible, the electronic effect of the
N
6
-substituent is prevailing. That was supported by calculations of Fukui functions and molecular orbital coefficients. Both descriptors indicated that the
N
7 atom was more nucleophilic than its
N
9-counterpart in all adenine anion derivatives. We demonstrated that selected substituents may shift the acylation of purines from a regioselective to a regiospecific mode. |
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ISSN: | 1860-5397 2195-951X 1860-5397 |
DOI: | 10.3762/bjoc.18.133 |