Discovery and enantiocontrol of axially chiral urazoles via organocatalytic tyrosine click reaction

Abstract

Axially chiral compounds play an important role in areas such as asymmetric catalysis. The tyrosine click-like reaction is an efficient approach for synthesis of urazoles with potential applications in pharmaceutical and asymmetric catalysis. Here we discover a class of urazole with axial chirality by restricted rotation around an N–Ar bond. By using bifunctional organocatalyst, we successfully develop an organocatalytic asymmetric tyrosine click-like reaction in high yields with excellent enantioselectivity under mild reaction conditions. The excellent remote enantiocontrol of the strategy originates from the efficient discrimination of the two reactive sites in the triazoledione and transferring the stereochemical information of the catalyst into the axial chirality of urazoles at the remote position far from the reactive site.

Organocatalytic Atroposelective Arylation of 2‐Naphthylamines as a Practical Approach to Axially Chiral Biaryl Amino Alcohols

“…We selected readily available N-sulfonyl iminoquinone 1a as the substrate instead of the quinone ester in the above-mentioned model reaction. Of the solvents investigated for the reaction catalyzed by CPA1 (Table 1, entries [11][12][13][14][15], DCM proved optimal. Then, various chiral phosphoric acid catalysts were screened but the results were inadequate ( Table 1, entries 2-10).…”

“…CPA1 was found to be the best catalyst in terms of the enantioselectivity for the model reaction. Of the solvents investigated for the reaction catalyzed by CPA1 ( Table 1, entries [11][12][13][14][15], DCM proved optimal. Having identified CPA1 as the best catalyst and DCM as the best solvent, we turned our attention to other reaction variables.Reducing the concentration had apositive effect on the enantioselectivity.W hen the DCM volume was doubled to 4mL, the ee of the product increased to 91 % (Table 1, entry 16).…”

Organocatalytic atroposelective synthesis of axially chiral styrenes

“…As part of our ongoing interest in asymmetric organocatalysis on construction of axially chiral compounds15275758, we describe herein the first organocatalytic atroposelective synthesis of axially chiral styrene compounds via direct Michael reaction of substituted diones/ketone esters/malononitrile to alkynals, providing a powerful and straightforward synthetic route toward substituted styrene derivatives. Such structural motifs are important chiral components for further transformations into biologically active natural products and pharmaceutical compounds and may have potential application in asymmetric catalysis as olefin ligands or organocatalysts.…”

Enantioselective syntheses of atropisomers featuring a five-membered ring

“…Another interesting prochiral atropisomeric scaffold concerns the N-arylurazole series 26 elegantly exploited by B. Tan and co-workers very recently (Scheme 11a). 29 They identified two structurally different bifunctional organocatalysts 27 and 31 for the enantioselective desymmetrisation of 26 resulting in the efficient revelation of the stereogenicity of the C-N bond with usually high level of enantioselectivity (86-99% ee). The use of the bifunctional thiourea 27 allowed the fast Friedel-Crafts type amination of naphthol-(phenol) derivatives 28 to give 29, while in sharp contrast, with indoles 30 only, chiral phosphoric acid 31…”