Graduate School of Engineering, Nagoya University, B2-3(611), Furo-cho, Chikusa, Nagoya, 464-8603, Japan.
Angew Chem Int Ed Engl. 2020 Sep 28;59(40):17641-17647. doi: 10.1002/anie.202007403. Epub 2020 Aug 11.
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 pK 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.
手性铜(II)配合物的催化对映选择性α-氟化反应是构建光学活性α-氟代羰基化合物最强大和有效的合成方法之一。然而，由于其α-氢原子的相对高的 pK 值以及在不发生差向异构化的情况下进行后续合成转化的困难，α-氟化α-直链羧酸衍生物仍然是一个巨大的挑战。在此，我们证明 3-(2-萘基)-L-丙氨酸衍生酰胺的手性铜(II)配合物是 N-(α-芳基乙酰基)和 N-(α-烷基乙酰基)3,5-二甲基吡唑的对映选择性和位点选择性α-氟化的高效催化剂。该转化的底物范围非常广泛(25 个例子，包括季碳α-氟代α-氨基酸衍生物)。α-氟代产物在几乎没有差向异构化的情况下转化为相应的酯、仲酰胺、叔酰胺、酮和醇，收率很高。
