42331-17-9Relevant articles and documents
Aryl nitrenium ions from N-alkyl-N-arylamino-diazonium precursors: Synthesis and reactivity
Huh, Chan Woo,Aube, Jeffrey
, p. 699 - 706 (2014)
A means of generating an N-alkyl-N-arylaminodiazonium ion, which then loses nitrogen to form a reactive aryl nitrenium intermediate, is described. In this sequence, a set of triazenyl acetonitriles was synthesized by nucleophilic addition of a nitrile anion to an aryl azide followed by temperature-dependent alkylation at either of two nucleophilic triazenyl nitrogen atoms. An α,α-disubstituted acetonitrile and N-arylaminodiazonium moiety (or aryl nitrenium ion upon loss of N2) are embedded in the resulting 1,3,3-trisubsituted triazene, which undergoes liberation and recombination of these two components under acidic conditions to yield an α-arylated acetonitrile containing an all-carbon-quaternary center. We propose that the N-alkyl-N-arylaminodiazonium ion loses nitrogen to generate an aryl nitrenium species, which then reacts with an α,α-disubstituted acetonitrile either at the para- or meta-position of the aromatic ring to afford p-alkylaminoaryl acetonitrile derivatives or 3,3-substituted 1-methylindolin-2-imines, depending on the substrates and conditions.
Enantiodivergent α-Amino C-H Fluoroalkylation Catalyzed by Engineered Cytochrome P450s
Zhang, Juner,Huang, Xiongyi,Zhang, Ruijie K.,Arnold, Frances H.
supporting information, p. 9798 - 9802 (2019/07/04)
The introduction of fluoroalkyl groups into organic compounds can significantly alter pharmacological characteristics. One enabling but underexplored approach for the installation of fluoroalkyl groups is selective C(sp3)-H functionalization due to the ubiquity of C-H bonds in organic molecules. We have engineered heme enzymes that can insert fluoroalkyl carbene intermediates into α-amino C(sp3)-H bonds and enable enantiodivergent synthesis of fluoroalkyl-containing molecules. Using directed evolution, we engineered cytochrome P450 enzymes to catalyze this abiological reaction under mild conditions with total turnovers (TTN) up to 4070 and enantiomeric excess (ee) up to 99%. The iron-heme catalyst is fully genetically encoded and configurable by directed evolution so that just a few mutations to the enzyme completely inverted product enantioselectivity. These catalysts provide a powerful method for synthesis of chiral organofluorine molecules that is currently not possible with small-molecule catalysts.
Direct ortho-Selective Amination of 2-Naphthol and Its Analogues with Hydrazines
Jia, Lei,Tang, Qiang,Luo, Meiming,Zeng, Xiaoming
, p. 5082 - 5091 (2018/05/15)
Described herein is a regioselective ortho-amination of 2-naphthol and its analogues with substituted hydrazines. It provides a direct methodology for the synthesis of N-arylaminated naphthol derivatives without the formation of related 1,1′-biaryl-2,2′-diamine or carbazole byproducts. Specifically, using N,N-disubstituted hydrazine precursors, N-unsubstituted ortho-aminated derivatives and related secondary amines can be formed in ethylene glycol in moderate to excellent yields. Variation of substrates to N,N′-diarylhydrazines and N-methyl-N,N′-diarylhydrazines led to N-aryl-1-amino-2-naphthol compounds. It is noted that biologically interesting indazole motifs can be facilely created by the reaction of N,N′-dialkylhydrazines with 2-naphthols. These ortho-amination reactions have the advantage of one-pot operation without the use of transition metal catalysts.
