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Substituent effects on conformational preference in α ‐substituted α ‐fluorophenylacetic acid methyl ester model systems for chiral derivatizing agents
Author(s) -
Sahnoun Riadh,
Fujimura Yuichi,
Kabuto Kuninobu,
Takeuchi Yoshio,
Noyori Ryoji
Publication year - 2009
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.1537
Subject(s) - chemistry , natural bond orbital , stereocenter , steric effects , substituent , stereochemistry , asymmetric carbon , fluorine , computational chemistry , density functional theory , crystallography , organic chemistry , enantioselective synthesis , optically active , catalysis
In connection with study of chiral derivatizing agents (CDAs) for NMR determination of absolute configuration of organic compounds, factors controlling the conformational preference between syn ‐ and anti ‐forms in α ‐substituted α ‐fluorophenylacetic acid methyl ester (FC(X)(Ph)COOMe) model systems were theoretically investigated. Substituents X at the stereogenic carbon atom were X = H, CCH and CH 3 , the electronic and steric properties of which were significantly different from each other. The model system with X = CCH and that with X = CH 3 were found to be possible candidates for fluorine‐containing CDAs. The syn conformation is stable compared with the anti one by 0.7 kcal mol −1 for the ester with X = CCH. On the other hand, the anti conformation is stable compared with the syn one by 0.5 kcal mol −1 for the ester with X = CH 3 . Both natural bond orbital (NBO) analysis and deletion of selected orbitals based on the donor–acceptor NBO scheme were adopted for semi‐quantitative estimation of factors responsible for the conformational preference as well as a qualitative inspection of occupied canonical molecular orbitals (MOs). It was shown that [ σ –( σ * + π *)(CO)] and [ σ – σ *(Ph) and π (Ph)– σ *] hyperconjugations are the main factors controlling the conformational preferences between the syn and anti conformations. Other types of effects such as electrostatic effects were also investigated. The role of the fluorine atom was also clarified. Copyright © 2009 John Wiley & Sons, Ltd.