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Fluorine⋅⋅⋅ and π⋅⋅⋅Alkali Metal Interactions Control in the Stereoselective Amide Enolate Alkylation with Fluorinated Oxazolidines (Fox) as a Chiral Auxiliary: An Experimental and Theoretical Study
Author(s) -
Sini Gjergji,
Tessier Arnaud,
Pytkowicz Julien,
Brigaud Thierry
Publication year - 2008
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200701604
Subject(s) - diastereomer , alkylation , chiral auxiliary , amide , chemistry , stereoselectivity , metal , fluorine , alkali metal , medicinal chemistry , computational chemistry , stereochemistry , organic chemistry , enantioselective synthesis , catalysis
The α‐alkylation of amide enolates by using a pseudo‐ C 2 symmetry trans 4‐phenyl‐2‐trifluoromethyloxazolidine ( trans ‐ Fox ) as a chiral auxiliary occurs with an extremely high diastereoselectivity (>99 % de). The origin of this excellent stereocontrol was investigated by an experimental and theoretical (DFT) study. With this trans chiral auxiliary, both F⋅⋅⋅metal and π⋅⋅⋅metal interactions compete to give the same diastereomer through Re face alkylation of the enolate. A 5.5 kcal mol −1 energy difference found between the Re face and the Si face attack transition states is consistent with the complete diastereoselectivity that has been experimentally achieved. On the other hand, in the case of the cis chiral auxiliary ( cis ‐ Fox ) the competition between the F⋅⋅⋅metal and π⋅⋅⋅metal interactions is unfavourable to the diastereoselectivity. In this case, the Re face and the Si face attack transition states were found to be nearly isoenergetic (0.3 kcal mol −1 difference), which is in good agreement with the very low diastereoselectivity observed.