Highly atroposelective synthesis of nonbiaryl naphthalene-1,2-diamine N-C atropisomers through direct enantioselective C-H amination

Abstract

Nonbiaryl N-C atropisomer is an important structural scaffold, which is present in natural products, medicines and chiral ligands. However the direct enantioselective C-H amination to access optically pure N-C atropisomer is still difficult and rare. Here we report a π-π interaction and dual H-bond concerted control strategy to develop the chiral phosphoric acids (CPAs) catalyzed direct intermolecular enantioselective C-H amination of N-aryl-2-naphthylamines with azodicarboxylates as amino sources for the construction of atroposelective naphthalene-1,2-diamines. This type of N-C atropisomers is stabilized by intramolecular hydrogen bond and the method features a broad range of substrates, high yields and ee values, providing a strategy to chirality transfer via the modification of N-C atropisomers.

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

“…Interestingly, subjection of the N-amination triazane product 4a into the optimal conditions without adding azodicarboxylate 2 also gave the para -amination product 3a in 58% yield with 98% ee after 16 h, with the aniline substrate 1a isolated in 28% yield, which suggested the reversible nature of the triazane formation step (Scheme 5B). Based on the above-mentioned experimental study and previous work (Bai et al., 2019, Drouet et al., 2011, Dumoulin et al., 2015), a plausible reaction mechanism is proposed, in which bifunctional activation (Parmar et al., 2014, Simón and Goodman, 2008, Yamanaka et al., 2007) of both the aniline substrate and azodicarboxylate via dual hydrogen-bonding interaction with the CPA catalyst is postulated (Scheme 5C). Under the catalysis of CPA catalyst, there are two alternative reaction pathways between aniline substrates and azodicarboxylates: (1) direct nucleophilic addition of the –NH 2 group to the azodicarboxylate facilitated the generation of the triazane products (path a), which is also reversible under these conditions; and (2) the para -selective amination of aniline substrates would give the dearomatized addition product INT A , possessing a chiral center (path b).…”

“…Asymmetric Friedel-Crafts aminations of naphthols and naphthylamines with azodicarboxylates have been well employed in asymmetric synthesis of N-containing chiral scaffolds. For instance, Jørgensen group (Brandes et al., 2006a, Brandes et al., 2006b) and Zhang group (Bai et al., 2019) developed asymmetric construction of C-N axial chirality by chiral amine and phosphoric acid-catalyzed ortho -amination of 2-naphthols and 2-naphthyl amines, respectively (Scheme 1A). 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).…”

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

“…Owing to the presence of axially chiral indole-based biaryl scaffolds such as naphthylindoles and phenylindoles in bioactive molecules and chiral catalysts [ 62 – 64 ], the construction of this scaffold has recently become valuable and attracted the attention of chemists [ 2 , 64 ]. In this context, Shi and co-workers reported a new strategy for the enantioselective synthesis of axially chiral naphthylindoles via the asymmetric addition reaction of racemic naphthylindole 42 with azodicarboxylate 43 under chiral phosphoric acid catalysis.…”

“…In general, the electronic properties of the substituents did not affect the stereoselectivity of the reaction. The mechanistic study revealed that, CPA 15 simultaneously activates N -phenyl-2-naphthylamine and azodicarboxylate through a dual hydrogen bond activation mode and a π–π interaction strategy ( Scheme 31 ) [ 2 ].…”

“…Axial chirality is one of the most important properties of nature, resulting from the nonplanar arrangement of four groups in pairs about a chirality axis. These include atropisomerism [ 1 ], chiral allenes, spiranes, spiroindanes, and so on [ 2 – 3 ]. Recently, there emerged an enormous demand for enantiopure compounds, not only for pharmaceutical and fine chemical industries, but also for fragrance, flavor, agrochemical, and food industries [ 4 ].…”