Hexafluoro‐2‐propanol Promotes para‐Selective C–H Amination of Free Anilines with Azodicarboxylates

Abstract

An effective, mild, and clean method for the C–H amination of free anilines with azodicarboxylates in 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFIP) without the need for any additional catalysts or reagents was developed. The reaction was found to be highly regioselective and provided a series of p‐aminophenylhydrazine derivatives in excellent yields. Moreover, compatibility with a free amino group makes this protocol an attractive strategy in synthetic chemistry.

Atroposelective Synthesis of Biaryl Diamines and Amino Alcohols via Chiral Phosphoric Acid Catalyzed para-Aminations of Anilines and Phenols

“…Interestingly, in the presence of CPA catalyst A1 (10 mol %), the amination reaction between 1a and azodicarboxylate 2 (1.1 equiv.) in toluene (with 5 Å molecular sieves) proceeded smoothly at ambient temperature to afford the triazane 4a (Egger et al., 1983, Tang et al., 2017) as the major product (60% yield), whereas the desired para -amination product 3a was obtained only in 13% yield with 47% enantiomeric excess (ee) (entry 1). Next, a variety of BINOL-derived chiral phosphoric acid catalysts were examined (entries 2–7), and encouragingly the TCYP catalyst (cat A7 ) provided the desired product 3a in 80% yield with 98% ee, with the undesired N -amination product 4a and diamination product 5a isolated in <10% yield (entry 7).…”

“…You group (Wang et al., 2015, Xia et al., 2019) and Luan group (Nan et al., 2015) reported asymmetric dearomatization of naphthols via direct aminations of naphthols with azodicarboxylates enabled by chiral Brønsted/Lewis acid catalysis, constructing N-containing chiral quaternary centers (Scheme 1B). Nevertheless, most of these methods are still limited to ortho -aminations of naphthols and naphthylamines; asymmetric reactions involving para -aminations of common anilines and phenols (Leblanc and Boudreault, 1995, Tang et al., 2017, Yadav et al., 2002, Zaltsgendler et al., 1993) are still elusive. Herein, we report a versatile protocol for atroposelective synthesis of biaryl diamines and amino alcohols via para -aminations of anilines and phenols (Diener et al., 2015, Gustafson et al., 2010, Miyaji et al., 2015, Miyaji et al., 2017, Mori et al., 2013a, Mori et al., 2013b) with azodicarboxylates via chiral phosphoric acid catalysis (Akiyama, 2007, Akiyama et al., 2004, Akiyama and Mori, 2015, Li and Song, 2018, Parmar et al., 2014, Terada, 2010, Uraguchi and Terada, 2004) (Scheme 1C).

Scheme 1Asymmetric Friedel-Crafts Amination with Azodicarboxylates(A) construction of C-N axial chirality, (B) construction of N-containing chiral quaternary centers, and (C) atroposelective synthesis of biaryl diamines and amino alcohols.

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Fluorinated Alcohols: Magic Reaction Medium and Promoters for Organic Synthesis

“…Crousse and co‐workers have developed an electrophilic amination of free anilines 69 , using azodicarboxylates 70 as electrophiles (Scheme ) . A series of p ‐aminophenylhydrazine derivatives were assembled in excellent yields and high regioselectivities.…”

“…Crousse and co-workers have developed an electrophilic amination of free anilines 69, using azodicarboxylates 70 as electrophiles (Scheme 23). [44] A series of p-aminophenylhydrazine derivatives were assembled in excellent yields and high regioselectivities. Owing to HFIP-azodicarboxylate association, the reaction could only occured at the para-position of aniline, which was sterically less hindrance.…”

Direct Amination of Arenes with Azodicarboxylates Catalyzed by Bisulfate Salt/HFIP Association

“…8 Recently, the amination of anilines with azodicarboxylates in HFIP under mild conditions has been reported by our group (Scheme 1c). 9 Given the importance of the amination of aromatics, we sought to optimize conditions for aromatics of weak reactivity (Scheme 1d). We turned toward mild conditions that are easy to implement in the presence of weaker acid catalysts than TFA or TfOH because HFIP can further enhance their acidity by the hydrogen network.…”