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We present a method for the amination of enolizable and non-enolizable ketones in the alpha (or beta) position to the carbonyl group. This approach is based on the conversion of the corresponding cyanohydrins to carbonazidates, precursors for thermal intramolecular nitrene insertion reactions into the adjacent C-H bond. Hydrolysis of the resulting carbamates under basic conditions with simultaneous regeneration of the carbonyl group yields amino ketones.
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http://dx.doi.org/10.1039/d5ob00009b | DOI Listing |
Org Biomol Chem
March 2025
Charles University, Faculty of Science, Department of Organic Chemistry, Hlavova 8, 12840 Praha, Czech Republic.
We present a method for the amination of enolizable and non-enolizable ketones in the alpha (or beta) position to the carbonyl group. This approach is based on the conversion of the corresponding cyanohydrins to carbonazidates, precursors for thermal intramolecular nitrene insertion reactions into the adjacent C-H bond. Hydrolysis of the resulting carbamates under basic conditions with simultaneous regeneration of the carbonyl group yields amino ketones.
View Article and Find Full Text PDFBeilstein J Org Chem
September 2024
Faculty of Bioorganic Chemistry, Wrocław University of Science and Technology, wyb. Wyspiańskiego 27, 50-370 Wrocław, Poland.
The study presents a novel approach utilizing iminium salt activation and mild enolization of thioesters, offering an efficient and rapid synthesis of Michael adducts with promising stereoselectivity and marking a significant advancement in mechanocatalysis. The stereoselective addition of bisthiomalonates - to cyclic enones and 4-chlorobenzylideneacetone proceeds stereoselectively under iminium activation conditions secured by chiral primary amines, in contrast to oxo-esters as observed in dibenzyl malonate addition. Mild enolization of thioesters allows for the generation of Michael adducts with good yields and stereoselectivities.
View Article and Find Full Text PDFACS Catal
August 2024
Department of Chemistry, The University of British Columbia, Vancouver, British Columbia V6T 1Z1, Canada.
Palladium-catalyzed cross-couplings remain among the most robust methodologies to form carbon-carbon and carbon-heteroatom bonds. In particular, carbon-nitrogen (C-N) couplings (Buchwald-Hartwig aminations) find widespread use in fine chemicals industries. The use of base in these reactions is critical for catalyst activation and proton sequestration.
View Article and Find Full Text PDFJ Org Chem
December 2023
School of Chemistry, Indian Institute of Science Education and Research, Thiruvananthapuram, Kerala 695551, India.
A novel and highly selective 5--- aldol condensation of 6-ketoaldehydes is presented using a proline-based alkylphosphonium ion catalyst. Bulky and oxophilic phosphonium ion plays a vital role in facilitating kinetic aldenamine formation and activating keto groups for aldol addition. This innovative approach exclusively targets five-membered carbo- and heterocyclic aldehydes, involving unusual aldehydes as donors and ketones as acceptors.
View Article and Find Full Text PDFJ Org Chem
February 2023
State Key Laboratory of Natural Medicines, School of Science, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
A new synthesis of functionalized 2-pyran-2-ones has been developed through N-heterocyclic carbene-catalyzed formal [3 + 3] annulation of alkynyl esters with enolizable ketones. The key to the success of this protocol relies on the use of an NHC instead of a tertiary amine as the catalyst. This protocol also features a broad substrate scope and mild metal-free conditions, offering simple and rapid access to the target molecules in a highly regioselective manner.
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