An official website of the United States government
Abstract A practical protocol for the first regiodivergent asymmetric addition of aryl and alkenyl organometallic reagents to substitutedN‐alkyl pyridinium heterocycles is described. The couplings proceed with high regiochemical and stereochemical selectivities, and provide access to chiral 1,2,3‐ and 1,3,4‐trisubstituted dihydropyridine products, controlled by judicious choice of nitrogen activating agent. To this end, a correlation was found between the parameterized size of the activating group and the C2/C4 regioselectivity in the couplings. The utility of the described chemistry was demonstrated in two concise asymmetric syntheses of (+)‐N‐methylaspidospermidine and (−)‐paroxetine.
more »
« less
Note: When clicking on a Digital Object Identifier (DOI) number, you will be taken to an external site maintained by the publisher.
Some full text articles may not yet be available without a charge during the embargo (administrative interval).
What is a DOI Number?
Some links on this page may take you to non-federal websites. Their policies may differ from this site.
-
-
Free, publicly-accessible full text available July 14, 2026
-
This article describes the first enantioselective synthesis of the Tasmanian marine alkaloid (+)-cylindricine B. The concise construction of the compound hinged on dearomative retrosynthetic logic combined with a tactical advance in the generation of congested, cyclic, alpha-tertiary amine centers. The scope of this key coupling reaction was explored in addition to providing a synthetic application for Cu-catalyzed enantioselective dearomatization of N-acyl-pyridiniums. The synthesis proceeds in five or six steps from commercially available starting materials.more » « less
-
Recent developments in the isotopic labeling of heteroarenes may prove to be useful in the realms of biomedical science, materials chemistry, and fundamental organic chemistry. The use of the age-old Zincke reaction, or tactical variants thereof, has become particularly utilitarian in effecting single-atom nitrogen replacement in various azines to generate their desired isotopologues. This chemistry can be synthetically leveraged at an early stage for diversity-oriented heterocyclic labeling of pharmaceuticals and/or natural products. Additionally, given the prevalence of saturated azacycles in biologically relevant molecules, access to these isotopologues becomes relevant through dearomative retrosynthetic analysis from the corresponding 15N-labeled heteroarenes.more » « less
-
A synthesis of the natural product thebaine is reported in eight steps from commercially available starting materials, hinging on the dearomatization and coupling of simple aromatic starting materials. This provides divergent access to two unnatural opioid derivatives and is aimed at the long-term development of synthetic opioid analogs of the “wonderdrug” Naloxone. Additionally, a formal enantioselective synthesis of all reported targets is disclosed that leverages a catalytic asymmetric dearomatization via anion-pairing catalysis.more » « less
