A5059572556- Catalytic Alkyne Reactions
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Synthetic Organic Chemistry Methods
- Oxidative Organic Chemistry Reactions
- Cyclopropane Reaction Mechanisms
- Catalytic Cross-Coupling Reactions
- Catalytic C–H Functionalization Methods
- Asymmetric Hydrogenation and Catalysis
- Asymmetric Synthesis and Catalysis
- Chemical Synthesis and Reactions
- Chemical Synthesis and Analysis
- Traditional and Medicinal Uses of Annonaceae
- Marine Sponges and Natural Products
- Chemical synthesis and alkaloids
- Inflammasome and immune disorders
- Ion Channels and Receptors
- Organoboron and organosilicon chemistry
- Synthesis and Catalytic Reactions
- Molecular spectroscopy and chirality
- N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
- Histone Deacetylase Inhibitors Research
- Fluorine in Organic Chemistry
- Synthesis and Reactions of Organic Compounds
- Mesoporous Materials and Catalysis
Janssen (Belgium)
2024
University of Hertfordshire
2024
Janssen (United Kingdom)
2023
MSD (UK) Limited (United Kingdom)
2014-2021
University of Cambridge
2007-2013
Universidad de Oviedo
2002-2009
Straightforward and efficient: Functionalized eight-membered carbocycles are easily obtained from simple allyl-substituted 5-hexyn-1-ol derivatives by a catalytic tandem sequence involving 6-exo cycloisomerization followed Prins-type cyclization (see scheme). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z503874_s.pdf or author. Please note: The publisher not responsible content functionality of any supporting supplied...
Abstract An efficient method for the synthesis of [3.3.1]bicyclic compounds from easily available alkynol derivatives has been developed. The reaction is based on a gold‐ or platinum‐catalyzed tandem process that involves an intramolecular hydroalkoxylation triple bond followed by Prins‐type cyclization. carried out with differently substituted and oxygen‐, nitrogen‐, carbon‐centered nucleophiles. incorporation halogen atoms as nucleophiles elimination reactions also studied....
Herein, we describe nickel oxidative addition complexes (Ni-OACs) of drug-like molecules as a platform to rapidly generate lead candidates with enhanced C(sp3) fraction. The potential Ni-OACs access new chemical space has been assessed not only in C(sp2)–C(sp3) couplings but also additional bond formations without recourse specialized ligands and improved generality when compared Ni-catalyzed reactions. development an automated diversification process further illustrates the robustness...
At sixes and sevens: The synthesis of [4.2.1]- [3.2.1]-fused bicyclic acetals by an intramolecular double alkoxylation alkyne diols is reported. course the reaction depends on substitution triple bond. Terminal alkynes give [3.2.1]bicyclic product a 6-exo pathway, whereas aryl undergo almost exclusively 7-endo cyclization to [4.2.1]bicycles (see scheme, Ts=toluene-4-sulfonyl). Supporting information for this article available WWW under...
Herein, we report an end-to-end process including synthesis, work-up, purification, and post-purification with minimal human intervention using Negishi coupling as a key transformation to increase Fsp3 in bioactive molecules. The main advantages of this protocol are twofold. First, the automated sequential generation organozinc reagents from readily available alkyl halides offers large diversity groups functionalize (hetero)aryl halide scaffolds via Pd-catalyzed continuous flow. Second,...
Progressive cycling! Highly functionalized benzofused oxabicyclo[3.3.1]nonanes are easily obtained from simple aryl-substituted alquinol derivatives by a catalytic tandem sequence involving an hydroalkoxylation reaction followed hydroarylation process, shown here.
Strained bicyclic substructures such as bicyclo[1.1.1]pentylamines (BCPAs) are increasingly targeted in medicinal chemistry arylamine bioisosteres. Here, we leverage high-throughput automated synthesis to rapidly develop library-amenable reaction conditions and maximize design space expand access BCPAs. This new protocol relies on a copper-mediated C–N coupling approach uses accessible bench-stable iodo-BCP building blocks. Its applicability has been exemplified by incorporating BCPs...
Herein, we present a novel class of diazo compounds as atomic carbon reagents substituted with two orthogonal redox-active leaving groups that were exploited in the late-stage construction chiral centers aryl C–H bonds from aromatic feedstocks and drug molecules. Key to strategy was use photoredox catalysis enable an initial diazomethylation reaction able generate diazomethyl-substituted esters. Subsequent readily available starting materials proceeded using broad range well-known ester...
Fischer carbene complexes have been implied as intermediates in a catalytic tandem process for the synthesis of cyclic compounds, including eight-membered carbocycles, excellent yields from alkynols (see scheme). The method was optimized to avoid use large quantities metallic species, thus overcoming one main limitations complexes. Supporting information this article is available on WWW under http://www.wiley-vch.de/contents/jc_2002/2005/z461414_s.pdf or author. Please note: publisher not...
Schlag auf Schlag: Funktionalisierte achtgliedrige Carbocyclen sind direktem Weg aus einfachen allylsubstituierten 5-Hexin-1-ol-Derivaten zugänglich. Dies gelingt durch eine katalytische Tandemsequenz 6-exo-Cycloisomerisierung und Prins-Cyclisierung (siehe Schema). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2006/z503874_s.pdf or from author. Please note: The publisher not responsible content functionality of any supporting...
Abstract The [W(CO) 5 ]‐catalyzed cycloisomerization reaction of 1,1‐disubstituted 4‐pentyn‐1‐ol derivatives has been studied from both, an experimental and theoretical point view. Three different catalytic systems have evaluated {preformed [(thf)W(CO) ], 6 ]/excess Et 3 N, ]/2 mol % N]. We found that the proceeds to give formal endo ‐ or exo ‐cycloisomerization products depending on amount N used substitution along alkyl chain starting alkynol. study allowed us find mechanisms reactions...
Abstract The AuCl 3 ‐catalyzed double hydroalkoxylation of conjugated 7‐hydroxyheptynoates offers a convenient route for the synthesis six‐membered cyclic acetals, which are common substructures polyketide natural products. When 6‐hydroxyhexynoates used as starting materials, either five‐membered E ‐enol ethers or corresponding acetals can be obtained by simply choosing appropriate reaction solvent. NMR spectroscopic studies were carried out to determine kinetics and pathway latterdomino 5‐...
Fischer-Carbenkomplexe treten vermutlich als Zwischenstufen in einem katalytischen Tandemprozess auf, der ausgezeichneten Ausbeuten Alkinole cyclische Verbindungen, darunter auch achtgliedrige Carbocyclen, überführt (siehe Schema). Es werden keine großen Mengen Metallspezies gebraucht, was eine Haupteinschränkungen von Fischer-Carbenkomplexen beseitigt. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2005/z461414_s.pdf or from...
New solvent-assisted mechanistic routes were located for the (THF)W(CO)5-promoted endo- and exo-cycloisomerization of 4-pentyn-1-ol using B3LYP/6-31G* (with LANL2DZ relativistic pseudopotential W) theory level. A mixed model was used by explicitly including a THF molecule as component reactive system taking into account effect bulk solvent means PCM-UAHF method. This plays crucial role making endo route leading to cyclic carbene complex most favorable one because an important catalytic...
Eight-membered carbocycles with up to five new stereogenic centers are enantioselectively obtained following a one-pot procedure that involves the coupling of three components: an alkenyl Fischer carbene complex, ketone enolate, and allyl lithium.
Sechs oder sieben: Die doppelte intramolekulare Alkoxylierung von Alkindiolen führt zu [4.2.1]- und [3.2.1]bicyclischen Acetalen, wobei der Reaktionsverlauf vom Substitutionsmuster Dreifachbindung abhängt. Terminale Alkine ergeben nach dem 6-exo-Modus [3.2.1]Bicyclen, Arylalkine reagieren fast ausschließlich unter 7-endo-Cyclisierung den [4.2.1]Bicyclen (siehe Schema, Ts = Toluol-4-sulfonyl).
The development and execution of a practical asymmetric synthesis the estrogen receptor beta selective agonist (8R,10aS)-6-(trifluoromethyl)-8,9,10,11-tetrahydro-8,10a-methanocyclohepta[1,2]indeno[4,5-d][1,2,3]triazol-7(3H)-one is described. optimized route features key chiral auxiliary-mediated dialkylation approach to set all-carbon quaternary center with exceptional stereocontrol. Overall, chemistry has been used prepare >30 kg drug candidate in 21% overall yield through 13 longest linear...
Process development to improve synthetic access a potent, selective, and brain-penetrant tricyclic diazepine clinical candidate that inhibits mutant IDH1 is described. A variety of disconnections were evaluated determine the preferred sequence fragment coupling. The optimized route involves metal-catalyzed C–N coupling/reductive cascade form central core, improved entries both zigzag morpholine cyclohexyl acid peripheral pieces, an efficient end-game acylation, coupling, deprotection. In...
Copper makes the difference: An umpolung reactivity of Michael acceptors is observed when alkenyl carbene complexes react with copper ketone enolates and electrophiles. This reaction allows straightforward synthesis functionalized three-component coupling products in a completely regio- diastereoselective way.
An improved route to the EF fragment of spongistatins has been developed and employed in a synthesis spongistatin 2. The C48–C51 diene side chain, which lacks chlorine substituent present 1, presented some compatibility issues during target assembly. These were overcome by implementing late stage Stille cross coupling construct portion natural product.
Azeotropic reflux chromatography (in which the eluent is continuously recycled by means of refluxing) was used to separate a mixture spiroketal intermediates in scale-up synthesis spongistatin 1, leading an improved separation and approximately 35-fold reduction amount solvent used.
Nickel catalysis has emerged as a powerful technique for streamlining the access to exceedingly complex organic molecules from simple precursors. However, nickel-catalyzed cross-couplings with advanced synthetic intermediates still remain considerable challenge. Herein, we describe based on utilization of nickel oxidative addition complexes (Ni-OAC) drug-like platform rapidly and reliably generate lead candidates enhanced C(sp3) fraction. The potential Ni-OACs new chemical space been...
Despite the prevalence of morpholine derivatives and bridged heterocycles in medicinally relevant compounds, bicyclic morpholines remain scarce because challenges associated with their synthesis. MRK A, an IDH1mut inhibitor for treatment glioma, derives its potency part from substitution a zigzag 2,5-bicyclic morpholine, 2-oxa-5-azabicyclo[2.2.2]octane, at C8. While existing entries suffered low yields lack stereochemical control, we developed concise stereospecific routes toward both...