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
Hauptverfasser: Toma, Mateja, Zubčić, Gabrijel, Lapić, Jasmina, Djaković, Senka, Šakić, Davor, Vrček, Valerije
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Sprache:eng
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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.
ISSN:1860-5397
2195-951X
1860-5397
DOI:10.3762/bjoc.18.133