Research on Chemicals and Custom Synthesis
The Georganics research department is actively engaged in organic chemistry research at an academic/university level. Our interest lies in fundamental research on new reaction cascades involving C-H activation/carbonylation, total syntheses of natural products, and flow chemistry.
Flow chemistry is utilized in the synthesis of natural products and in the optimisation of various reaction steps in the preparation of a range of different products.
The active participation of our research group members in problem solving current research challenges ensures that our knowledge expands for our custom synthesis/research programs or our customers.
Recent advances in the construction of isoindolo[2,1-a]indol/indolin-6-ones via C-C cross-coupling reactions
The review summaries the most recent synthetic methodologies for assembly of the 6H-isoindolo[2,1-a]indol-6-one and 10b,11-dihydro-6H-isoindolo[2,1-a]indol-6-one scaffolds, the structural motifs present in many natural and biologically interesting compounds. The literature covered in this overview dates from January 2015 to April 2020, and presented strategies are based on transition metal-catalysed C-C cross coupling reactions.
Recent Applications of Continuous Flow in Homogeneous Palladium Catalysis
Considerable advances have been made using continuous flow chemistry as an enabling tool in organic synthesis. Consequently, the number of articles reporting continuous flow methods has increased significantly in recent years. This review covers the progress achieved in homogeneous palladium catalysis using continuous flow conditions over the last five years, including C–C/C–N cross-coupling reactions, carbonylations and reductive/oxidative transformations.
Continuous Pd-Catalyzed Carbonylative Cyclization Using Iron Pentacarbonyl as a CO Source
This work discloses a continuous flow carbonylation reaction using iron pentacarbonyl as source of CO. The described transformation using this surrogate was designed for use in commonly accessible flow equipment. Optimized conditions were applied to a scalable synthesis of the natural compound isolated from perianal glandular pheromone secretion of the African civet cat. In addition, a flow Pd-catalyzed carbonylation of aryl halides is successfully reported.
One-Step Synthesis of Isoindolo[2,1-a]indol-6-ones via Tandem Pd-Catalyzed Aminocarbonylation and C–H Activation
A unified catalytic system for tandem Pd-catalyzed carbonylation and C–C cross-coupling via C–H activation was designed. The proposed cascade reaction allows a facile one-step construction of a tetracyclic isoindoloindole skeleton, in which three new C–C/C–N bonds are simultaneously formed. In detail, the carbonylation of aryl dibromides with indoles and C–H activation of in situ formed N-(2’-bromoaroyl)-indole provide biologically relevant 6H-isoindolo[2,1-a]indol-6-ones from commercially available substrates. The aminocarbonylation step in the proposed tandem reaction utilizes glyoxylic acid monohydrate as an environmentally friendly CO surrogate.
A Short Asymmetric Synthesis of Sauropunols A–D
A short and efficient asymmetric synthesis of natural sauropunols A, B, and C/D has been accomplished in 6 steps from divinylcarbinol with overall yield of 19%, 7% and 32%, respectively. The key synthetic steps include effective Sharpless asymmetric epoxidation of penta-1,4-dien-3-ol and a highly diastereoselective Pd-catalysed oxycarbonylation of pentene-1,2,3-triol. The structures of sauropunols A and B have been confirmed.
Glyoxylic Acid as a Carbon Monoxide Source for Carbonylation Reactions
A new protocol for the generation of carbon monoxide by the dehydration of glyoxylic acid has been developed. Glyoxylic acid was applied as an environmentally friendly and cheap substitute for toxic and gaseous CO in the palladium-catalyzed carbonylation reactions providing industrially interesting products in good to excellent yields.
Zn-Mediated Reduction of Oxalyl Chloride Forming CO and Its Application in Carbonylation Reactions
An efficient protocol for the generation of carbon monoxide by Zn-mediated reduction of oxalyl chloride has been developed. Oxalyl chloride was applied as an extremely effective substitute for toxic gaseous CO in the palladium-catalyzed alkoxy-/amino-/hydrogen-/hydroxycarbonylation processes providing industrially interesting esters, amides, aldehydes, and carboxylic acids in good to excellent yields. This new procedure can be applied to various carbonylation reactions in the presence of a transition metal catalyst under mild conditions and with a stoichiometric amount of CO source.
Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds
The study of Pd-catalysed cyclisation reactions of alkenols using different catalytic systems is reported. These transformations affect the stereoselective construction of mono- and/or bicyclic oxaheterocyclic derivatives depending on a starting alkenol. The substrate scope and proposed mechanism of Pd-catalysed cyclisation reactions are also discussed. Moreover, the diastereoselective Pd-catalysed cyclisation of appropriate alkenols to tetrahydrofurans and subsequent cyclisation provided properly substituted 2,5-dioxabicyclo[2.2.1]heptane and 2,6-dioxabicyclo[3.2.1]octane, respectively. Such bicyclic ring subunits are found in many natural products including ocellenynes and aurovertines.
A General Continuous Flow Method for Palladium Catalysed Carbonylation Reactions Using Single and Multiple Tube-in-Tube Gas-Liquid Microreactors.
A series of continuous flow chemistry processes that facilitate the palladium-catalysed carbonylation of aryl and vinyl iodides and aryl bromides with a range of alkoxy, hydroxy and amino nucleophiles is reported. Harnessing a semipermeable Teflon® AF-2400 Tube-in-Tube assembly, these reactors permit the controlled transport of carbon monoxide into solution at elevated pressure to generate homogeneous flow streams, avoiding some potential issues associated with segmented flow gas-liquid reactors. As the volume of pressurised gas contained within the device is low, the hazards associated with this are potentially mitigated relative to comparable batch processes. We also show how the incorporation of a second in-line gas-flow reactor allows for the sequential introduction of two gases (carbon monoxide and a gaseous nucleophile) into the reaction stream.