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Enantio‐ and Site‐Selective α‐Fluorination of N ‐Acyl 3,5‐Dimethylpyrazoles Catalyzed by Chiral π–Cu II Complexes
Author(s) -
Ishihara Kazuaki,
Nishimura Kazuki,
Yamakawa Katsuya
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202007403
Subject(s) - epimer , chemistry , catalysis , yield (engineering) , enantioselective synthesis , propionates , fluorine , hydrogen , substrate (aquarium) , organic chemistry , derivative (finance) , medicinal chemistry , combinatorial chemistry , stereochemistry , materials science , oceanography , metallurgy , geology , economics , financial economics
Catalytic enantioselective α‐fluorination reactions of carbonyl compounds are among the most powerful and efficient synthetic methods for constructing optically active α‐fluorinated carbonyl compounds. Nevertheless, α‐fluorination of α‐nonbranched carboxylic acid derivatives is still a big challenge because of relatively high p K a values of their α‐hydrogen atoms and difficulty of subsequent synthetic transformation without epimerization. Herein we show that chiral copper(II) complexes of 3‐(2‐naphthyl)‐ l ‐alanine‐derived amides are highly effective catalysts for the enantio‐ and site‐selective α‐fluorination of N ‐(α‐arylacetyl) and N ‐(α‐alkylacetyl) 3,5‐dimethylpyrazoles. The substrate scope of the transformation is very broad (25 examples including a quaternary α‐fluorinated α‐amino acid derivative). α‐Fluorinated products were converted into the corresponding esters, secondary amides, tertiary amides, ketones, and alcohols with almost no epimerization in high yield.