88912-03-2Relevant academic research and scientific papers
Enantioselective Synthesis of Chiral Amines via Biocatalytic Carbene N-H Insertion
Carminati, Daniela M.,Fasan, Rudi,Johnson, Nathan R.,Steck, Viktoria
, p. 10967 - 10977 (2020/11/23)
Optically active amines represent highly valuable building blocks for the synthesis of advanced pharmaceutical intermediates, drug molecules, and biologically active natural products. Hemoproteins have recently emerged as promising biocatalysts for the formation of C-N bonds via carbene transfer, but asymmetric N-H carbene insertion reactions using these or other enzymes have so far been elusive. Here, we report the successful development of a biocatalytic strategy for the asymmetric N-H carbene insertion of aromatic amines with 2-diazopropanoate esters using engineered variants of myoglobin. High activity and stereoinduction in this reaction could be achieved by tuning the chiral environment around the heme cofactor in the metalloprotein in combination with catalyst-matching and tailoring of the diazo reagent. Using this approach, an efficient biocatalytic protocol for the synthesis of a broad range of substituted aryl amines with up to 82% ee was obtained. In addition, a stereocomplementary catalyst useful to access the mirror-image form of the N-H insertion products was identified. This work paves the way to asymmetric amine synthesis via biocatalytic carbene transfer, and the present strategy based on the synergistic combination of protein and diazo reagent engineering is expected to prove useful in the context of these as well as other challenging asymmetric carbene transfer reactions.
Alkyl halide-free heteroatom alkylation and epoxidation facilitated by a recyclable polymer-supported oxidant for the in-flow preparation of diazo compounds
Nicolle, Simon M.,Hayes, Christopher J.,Moody, Christopher J.
supporting information, p. 4576 - 4579 (2015/03/18)
Highly reactive metal carbenes, generated from simple ketones via diazo compounds, including diazoamides and -phosphonates, using a recyclable reagent inflow, are transient but versatile electrophiles for heteroatom alkylation reactions and for epoxide formation. The method produces no organic waste, with the only byproducts being water, KI and nitrogen, without the attendant hazards of isolation of intermediate diazo compounds.
Enantioselective synthesis of α-secondary and α-tertiary piperazin-2- Ones and piperazines by catalytic asymmetric allylic alkylation
Korch, Katerina M.,Eidamshaus, Christian,Behenna, Douglas C.,Stoltz, Brian M.,Nam, Sangkil,Horne, David
supporting information, p. 179 - 183 (2015/02/05)
The asymmetric palladium-catalyzed decarboxylative allylic alkylation of differentially N-protected piperazin-2- ones allows the synthesis of a variety of highly enantioenriched tertiary piperazine-2-ones. Deprotection and reduction affords the corresponding tertiary piperazines, which can be employed for the synthesis of medicinally important analogues. The introduction of these chiral tertiary piperazines resulted in imatinib analogues which exhibited comparable antiproliferative activity to that of their corresponding imatinib counterparts.
Cytochrome P450-catalyzed insertion of carbenoids into N-H bonds
Wang, Z. Jane,Peck, Nicole E.,Renata, Hans,Arnold, Frances H.
, p. 598 - 601 (2014/01/17)
Expanding nature's catalytic repertoire to include reactions important in synthetic chemistry will open new opportunities for 'green' chemistry and biosynthesis. We demonstrate the first enzyme-catalyzed insertion of carbenoids into N-H bonds. This type of bond disconnection, which has no counterpart in nature, can be mediated by variants of the cytochrome P450 from Bacillus megaterium. The N-H insertion reaction takes place in water, provides the desired products in 26-83% yield, forms the single addition product exclusively, and does not require slow addition of the diazo component.
DIHYDROPTERIDINONES
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, (2013/05/23)
Compounds of Formula I, as shown below and defined herein: pharmaceutically acceptable salts thereof, synthesis, intermediates, formulations, and methods of disease treatment therewith, including treatment of cancers, such as tumors driven or mediated at
Well-defined binuclear chiral spiro copper catalysts for enantioselective N-H insertion
Zhu, Shou-Fei,Xu, Bin,Wang, Guo-Peng,Zhou, Qi-Lin
supporting information; experimental part, p. 436 - 442 (2012/03/07)
An asymmetric N-H insertion of α-diazoesters with anilines catalyzed by well-defined copper complexes of chiral spiro bisoxazoline ligands was studied in detail. The copper-catalyzed asymmetric N-H insertion of a wide range of α-alkyl-α-diazoacetates with anilines was accomplished with excellent enantioselectivity (up to 98% ee) and provided an efficient method for the preparation of optically active α-amino acid derivatives. A correlation study of the electronic properties of the substrates with the enantioselectivity of the N-H insertion reaction supports a stepwise insertion mechanism, and the significant first-order kinetic isotope effect proves that the proton transfer is most likely the rate-limiting step. A binuclear chiral spiro copper catalyst having 14-electron copper centers, a trans coordination model, a perfect C2-symmetric chiral pocket, and significant Cu-Cu interaction was isolated and extensively studied. The novel structure of the binuclear chiral spiro copper catalyst leads to unique reactivity as well as enantioselectivity in the N-H insertion reaction.
Iron(III) corroles and porphyrins as superior catalysts for the reactions of diazoacetates with nitrogen- or sulfur-containing nucleophilic substrates: Synthetic uses and mechanistic insights
Aviv, Iris,Gross, Zeev
scheme or table, p. 3995 - 4005 (2009/05/26)
A thorough mechanistic investigation has been performed on the reactions of primary and secondary amines with diazoacetates, which proceed uniquely quickly and efficiently when catalyzed by iron(III) corroles and porphyrins. Two major differences in relation to other metal-based catalysts are that the iron complexes are not poisoned by excess amine and that metal-carbene intermediates are apparently not involved in the reaction pathway. The results instead point towards nitrogen ylide intermediates formed by nucleophilic attack of the amines on diazoacetate-coordinated iron complexes. Nitrogen ylides are also formed when allyl- and propargylsubstituted tertiary amines react with diazoacetates, a scenario that smoothly leads to 2,3-rearrangement reaction products with catalytic amounts of the iron(III) complexes. Similar findings regarding the superiority of the iron-(III) complexes (in terms of catalyst loading, chemical yields, and reaction conditions) were obtained with thiols (S-H insertion) and sulfides (2,3-rear-rangement reactions), which suggest similar mechanisms operate in these cases.
Ruthenium-catalyzed one-pot carbenoid N-H insertion reactions and diastereoselective synthesis of prolines
Deng, Qing-Hai,Xu, Hai-Wei,Yuen, Angella Wing-Hoi,Xu, Zhen-Jiang,Che, Chi-Ming
supporting information; experimental part, p. 1529 - 1532 (2009/04/07)
Aryl- and aliphatic-substituted 3-hydroxyprolines and various other amino esters are conveniently prepared by [RuCI2(p-cymene)] 2-catalyzed one-pot intramolecular and intermolecular carbenoid N-H insertion reactions, respectively, and the prolines are formed with high diastereoselectivities. The catalytic reactions are tolerant toward air/moisture, and the product yields are insensitive to the organic solvents used.
Direct and indirect reductive amination of aldehydes and ketones with solid acid-activated sodium borohydride under solvent-free conditions
Byung, Tae Cho,Sang, Kyu Kang
, p. 5725 - 5734 (2007/10/03)
A simple and convenient procedure for reductive amination of aldehydes and ketones using sodium borohydride activated by boric acid, p-toluenesulfonic acid monohydrate or benzoic acid as reducing agent under solvent-free conditions is described.
Cu(I)-carbenoid- and Ag(I)-Lewis acid-catalyzed asymmetric intermolecular insertion of α-diazo compounds into N-H bonds
Bachmann, Stephan,Fielenbach, Doris,Jorgensen, Karl Anker
, p. 3044 - 3049 (2007/10/03)
Chiral Cu(I)-bisoxazoline- and Cu(I)-PN-complexes were found to catalyze the intermolecular insertion of α-diazo compounds into N-H bonds. The insertion reactions proceed with enantioselectivities of up to 28% ee for the different α-diazo acetates into one of the N-H bonds of different amines. Analogous chiral Ag(I) complexes were found to give higher enantioselectivities of up to 48% ee, however, lower yields were obtained. There are indications, that the Ag(I)-mediated reactions follow a different reaction mechanism compared to the Cu(I)-catalyzed insertions. It is demonstrated that different α-amino acid derivatives can be obtained via this approach in good yields and with low to moderate enantioselectivities. However, the results obtained are the highest asymmetric inductions obtained for an intermolecular N-H insertion via chiral carbene complexes or chiral Lewis acid catalysis.
