We feature an article from ACS Med Chem Lett. where seven different C(sp2)–C(sp3) cross-coupling methodologies are compared for highly functionalized substrates.
Julia is one of the most widely used reactions in organic synthesis. This is a new reagent for the Julia-Kocienski reaction, a modification of the original Julia reaction.
Diazomethane is a versatile reagent, used for mild methylations, homologations, [3+2] cycloadditions and metal-catalyzed cyclopropanations. Scores high in the atom economy…
The introduction of fluorine atoms is a widely used approach in medicinal chemistry. It can lead to drugs with improved potency and permeability, but what about its effect on metabolic pathways?
This work tackles, once again, one of the most used methods to carry out the nucleophilic substitution of alcohols in one step, the Mitsunobu reaction.
An interesting application of flow chemistry for the continuous synthesis of #indoles through the palladium-catalyzed deoxygenation of nitrostilbenes with CO as the reducing agent.
Phil S. Baran and his co-workers had made a reality above chemical dreams by the application of Li-ion battery chemistry in synthetic organic electroreduction.
A general alkyl-alkyl cross-coupling enabled by redox-active esters and alkylzinc reagents Activated esters of alkylic acids as building blocks for the…
Ni/Cu-Catalyzed Defluoroborylation of Fluoroarenes for Diverse C–F Bond Functionalizations Using a mixed catalytic system to promote the transformation of aromatic fluorides…
Multimetallic catalysed cross-coupling of aryl bromides with aryl triflates A catalytic system using two metals allows the synthesis of biaryl products…
A Fluorinated Ligand Enables Room-Temperature and Regioselective Pd-Catalyzed Fluorination of Aryl Triflates and Bromides The development of a new phosphine ligand…
Chemoselective Reductive Amination of Carbonyl Compounds for the Synthesis of Tertiary Amines Using SnCl2·2H2O/PMHS/MeOH A new protocol for a reductive amination…
Synthesis of Heteroaryl Sulfonamides from Organozinc Reagents and 2,4,6-Trichlorophenyl Chlorosulfate Access to sulfonated heterocycles using zincates and the reagent TCPC. It…
Aminocarbonylation of Aryl Tosylates to Carboxamides Generation of aromatic amides using CO, amines and aryl tosylates as coupling substrates. This is…
Practical olefin hydroamination with nitroarenes A new, powerful method to generate quaternary amines without using expensive catalysts. Baran has done it…
In Situ Generation of Difluoromethyl Diazomethane for [3+2] Cycloadditions with Alkynes Safe preparation of an elusive reagent, difluoromethyl diazomethane, and its…
Transition-Metal-Free Hydration of Nitriles Using Potassium tert-Butoxide under Anhydrous Conditions A simple, controlled hydrolisis of nitriles using potassium tert-butoxide. This is…
Palladium-Catalyzed, Ring-Forming Aromatic C–H Alkylations with Unactivated Alkyl Halides Formation of carbocycles and saturated heterocycles through a palladium mediated intramolecular radical…
Synthesis of Pyrazoles from 1,3-Diols via Hydrogen Transfer Catalysis A method for the synthesis of 1,4-disubstituted pyrazoles using ruthenium-catalyzed hydrogen transfer….
Engaging Nonaromatic, Heterocyclic Tosylates in Reductive Cross-Coupling with Aryl and Heteroaryl Bromides Reductive coupling of common aliphatic heterocycles (piperidines, pyrrolidines, pyranes…
Palladium-Catalyzed Coupling of Azoles or Thiazoles with Aryl Thioethers via C–H/C–S Activation Coupling of azoles and thiazoles with aryl thioeters when…
Condensed-Phase, Halogen-Bonded CF3I and C2F5I Adducts for Perfluoroalkylation Reactions An old reagent for trifluoromethylation turned user-friendly. It is a pity that…
Nickel-Catalyzed Decarboxylative Cross-Coupling of Perfluorobenzoates with Aryl Halides and Sulfonates Conditions to carry out a Suzuki-like coupling with perfluorinated benzoates. I…
A Practical Lewis Base Catalyzed Electrophilic Chlorination of Arenes and Heterocycles Mild chlorination method of arenes and heteroarenes. Here you have…
Metal-Catalyzed Azidation of Tertiary C–H Bonds Suitable for Late-Stage Functionalization Another entry in the wonderful world of the C-H activation, this…
Two-Step Cyanomethylation Protocol: Convenient Access to Functionalized Aryl- and Heteroarylacetonitriles Accesing (hetero)arylacetonitriles using no cyanide at all. If you search through…
PhenoFluorMix: Practical Chemoselective Deoxyfluorination of Phenols Improved reagent for the direct conversion of phenols into fluorides. In a previous blog entry…
Functionalized olefin cross-coupling to construct carbon-carbon bonds A new method for the generation of quaternary centers using Fe catalysis. Some years…
Overcoming the limitations of directed C–H functionalizations of heterocycles C-H activation on heterocycles, avoiding the activation of the C-H adjacent to…
Cu(II) Catalyzed Imine C–H Functionalization Leading to Synthesis of 2,5-Substituted 1,3,4-Oxadiazoles Here you have a simple method to prepare 2,5-substituted 1,3,4-oxadiazoles:…
Synthesis of Catechols from Phenols via Pd-Catalyzed Silanol-Directed C–H Oxygenation Synthesis of catechols using a silanol as activating group. Here you…
Ligand-Promoted C3-Selective Arylation of Pyridines with Pd Catalysts: Gram-Scale Synthesis of (±)-Preclamol Coupling of aryl halides with pyridines through a C3…
Regioselective Synthesis and Slow-Release Suzuki–Miyaura Cross-Coupling of MIDA Boronate-Functionalized Isoxazoles and Triazoles Preparation of boronic acid MIDA esters of isoxazoles and…
Synthesis of 2-(Trifluoromethyl)oxazoles from ß-Monosubstituted Enamines via PhI(OCOCF3)2-Mediated Trifluoroacetoxylation and Cyclization Synthesis of trifluoromethylated oxazoles from enamines and PIFA. If this…
Ni(COD)2/PCy3 Catalyzed Cross-Coupling of Aryl and Heteroaryl Neopentylglycolboronates with Aryl and Heteroaryl Mesylates and Sulfamates in THF at Room Temperature Coupling…
Nickel-Catalyzed Suzuki–Miyaura Reaction of Aryl Fluorides Coupling of fluoroaromatics with boronates using a Nickel catalyst. It is official: We can couple…
A Powerful Palladium-Catalyzed Multicomponent Process for the Preparation of Oxazolines and Benzoxazoles Synthesis of oxazolines and benzoxazoles through a new MCR….
Palladium-Catalyzed, Direct Boronic Acid Synthesis from Aryl Chlorides: A Simplified Route to Diverse Boronate Ester Derivatives Advances in the preparation of…
A Mild Negishi Cross-Coupling of 2-Heterocyclic Organozinc Reagents and Aryl Chlorides Improved procedure for the Negishi coupling. We have mentioned in…
A Multiligand Based Pd Catalyst for C-N Cross-Coupling Reactions Advances in the palladium catalyzed amination. Palladium catalyzed C-N bond formation is…
Regioselective Palladium-Catalyzed Arylation of 4-Chloropyrazoles A very nice demonstration of the DOE usefulness in drug discovery. Our readers will remember that…
An Efficient and General Method for the Heck and Buchwald–Hartwig Coupling Reactions of Aryl Chlorides Efficient Heck coupling and Buchwald-Hartwig amination…
Total Synthesis of (±)-Streptonigrin: De Novo Construction of a Pentasubstituted Pyridine using Ring-Closing Metathesis A total synthesis of Streptonigrin using a…
Multijet Oscillating Disc Millireactor: A Novel Approach for Continuous Flow Organic Synthesis A new concept for flow chemistry reactors. Flow chemistry…
Practical Radical Cyclizations with Arylboronic Acids and Trifluoroborates A practical radical cyclization using boronic acids and trifluoroborates. Hmmm, this came like…
Silver-Mediated Trifluoromethylation of Arenes Using TMSCF3 Introduction of the trifluoromethyl moiety into aromatic rings. And now by Sanford et al. (University…
Copper-Catalyzed C(sp3)–C(sp3) Bond Formation Using a Hypervalent Iodine Reagent: An Efficient Allylic Trifluoromethylation Introduction of the trifluoromethyl moiety in allylic positions….
Innate C-H trifluoromethylation of heterocycles Introduction of the trifluoromethyl moiety into heterocycles. I admit that I almost missed this paper. Honestly,…
Cross-Coupling of Mesylated Phenol Derivatives with Potassium Cyclopropyltrifluoroborate Cyclopropylation of aromatic rings using mesylates as starting materials. Another paper by Molander…
Synthesis of Cyclic Enones via Direct Palladium-Catalyzed Aerobic Dehydrogenation of Ketones Synthesis of cyclic enones with a Palladium catalyst. Stahl (University…
Use of Catalytic Fluoride under Neutral Conditions for Cleaving Silicon–Oxygen Bonds Catalytic protocols for the deprotection of silyl ethers using TBAF…
Construction of Carbocyclic Ring of Indoles Using Ruthenium-Catalyzed Ring-Closing Olefin Metathesis Synthesis of highly substituted indoles using a RCM approach. Yoshida…
Palladium-Catalyzed Carbonation–Diketonization of Terminal Aromatic Alkenes via Carbon–Nitrogen Bond Cleavage for the Synthesis of 1,2-Diketones Nitroalkanes and styrenes as raw materials…
Palladium-Catalyzed Carbon-Monoxide-Free Aminocarbonylation of Aryl Halides Using N-Substituted Formamides as an Amide Source An aminocarbonylation protocol to introduce directly amides. This…
Highly Efficient Synthesis of Phenols by Copper-Catalyzed Hydroxylation of Aryl Iodides, Bromides, and Chlorides Copper catalyzed hydroxylation of chloro-, bromo- and…
Direct Transformation of N,N-Dimethylformamide to -CN: Pd-Catalyzed Cyanation of Heteroarenes via C-H Functionalization Cyanation of protected, C-2 substituted indoles, without using…
Deoxyfluorination of Phenols Direct conversion phenols into fluorides with a new fluorination reagent. Ritter (Harvard University, Mass., USA) has published a…
Microwave-accelerated reductive amination between ketones and ammonium acetate Reductive amination under microwave irradiation conditions. Reductive Amination is probably one of the…
Microwave-Assisted Synthesis of Weinreb and MAP Aryl Amides via Pd-Catalyzed Heck Aminocarbonylation Using Mo(CO)6 or W(CO)6 Preparation of Weinreb amides from…
Transition-Metal-Free O-, S-, and N-Arylation of Alcohols, Thiols, Amides, Amines, and Related Heterocycles Introduction of nucleophiles using superbase. Looks like an…
Stereospecific Nickel-Catalyzed Cross-Coupling Reactions of Alkyl Ethers: Enantioselective Synthesis of Diarylethanes Ni-catalyzed replacement of methoxy groups. I must admit that when…
Water works: an efficient palladium-catalyzed cross-coupling reaction between boronic acids and bromoacetate with aminophosphine ligand Preparation of phenylacetic acids in water…
Enhanced reactivity of silver- and gold-catalysed hydrogenations using silver(I) salts Using gold and silver to hydrogenate halonitroaromatics. If you have ever…
An Opportunity for Mg-Catalyzed Grignard-Type Reactions: Direct Coupling of Benzylic Halides with Pinacolborane with 10 mol % of Magnesium Preparation of…
Palladium-Catalyzed Cross-Coupling of Aryl Chlorides and Tosylates with Hydrazine Finally, the direct introduction of hydrazine through a Buchwald-Hartwig coupling. The introduction…
PyDipSi: A General and Easily Modifiable/Traceless Si-Tethered Directing Group for C-H Acyloxylation of Arenes Remote functionalization using a silicon-tethered directing group….
A General and Efficient Catalyst for Palladium-Catalyzed C-O Coupling Reactions of Aryl Halides with Primary Alcohols Introduction of primary alcohols using…
Highly Regioselective Palladium-Catalyzed Direct Arylation of Oxazole at C-2 or C-5 with Aryl Bromides, Chlorides, and Triflates Switching the coupling position…
Manganese-catalyzed cross-coupling reactions of aliphatic amines with aryl halides Manganese-catalyzed introduction of aliphatic amines into aryl halides. Sometimes I think that…
A General Palladium Catalyst System for Suzuki-Miyaura Coupling of Potassium Aryltrifluoroborates and Aryl Mesylates More improvements on the Suzuki-Miyaura reaction partners….
Synthesis of Unnatural Amino Acid Derivatives via Palladium-catalyzed 1,4-Addition of Boronic Acids Take advantage of many boronic acids to get unnatural…
Direct Synthesis of Cbz-protected (2-Amino)-6-(2-aminoethyl)pyridines Construction of ethylamino chains over functionalized pyridines and other azoles. The importance of the 2-amino-6-(2-aminoethyl)pyridine skeleton…
Triethanolamine-Mediated Palladium-Catalyzed Regioselective C-2 Direct Arylation of Free NH-Pyrroles Arylation of pyrroles using a phosphine-free protocol. ‘C-H activation is one of…
Titanium(IV) Isopropoxide Mediated Synthesis of Pyrimidin-4-ones Synthesis of highly substituted pyrimidones from amides mediated by Titanium. The pyrimidin-4-one scaffold is widespread…
Iridium-Catalyzed a-Alkylation of Acetates with Primary Alcohols and Diols A method for the alkylation of acetates using Iridium. Aldolic condensation is…
N-Alkylation of poor nucleophilic amine and sulfonamide derivatives with alcohols by a hydrogen autotransfer process catalyzed by copper(II) acetate Alkylation of…
Synthesis of 2-Substituted Pyrazolo[1,5-a]pyridines through Cascade Direct Alkenylation/Cyclization Reactions Synthesis of fused pyrazoles by coupling with an activated C-H. If you…
Nickel-Catalyzed Reductive Cross-Coupling of Aryl Halides with Alkyl Halides Introduction of alkyl chains into aromatic rings catalyzed by Nickel. Transition-metal (Pd,…
Palladium-Catalyzed Preparation of Weinreb Amides from Boronic Acids and N-Methyl-N-methoxycarbamoyl Chloride A method for the preparation of Weinreb amides by palladium-catalyzed…
Zinc-Catalyzed Reduction of Amides: Unprecedented Selectivity and Functional Group Tolerance A mild, selective reduction of tertiary amides catalyzed by zinc acetate….
Meldrum’s acid is the trivial name for 2,2-dimethyl-1,3-dioxane-4,6-dione; this amazingly simple, symmetric molecule is a very interesting starting material for many…
Phenols, phenols, and phenols Three papers using phenols as starting materials for organometallics couplings. Phenols are ubiquitous products in nature. They…
Umpolung Amination: Nickel-Catalyzed Coupling Reactions of N,N-Dialkyl-N-chloroamines with Diorganozinc Reagents An inverted alternative to the usual Buchwald–Hartwig amination. There are two…
Palladium-Catalyzed Direct Carboxylation of Aryl Bromides with Carbon Dioxide A carbonylation reaction that uses CO2. The preparation of carboxylic acids through…
Zn-Mediated, Pd-Catalyzed Cross-Couplings in Water at Room Temperature Without Prior Formation of Organozinc Reagents Easy and wet protocol for the Negishi…
Iron Complex-Catalyzed N-Arylation of Pyrazoles under Aqueous Medium Interesting protocol for the iron-catalyzed coupling of pyrazoles in aqueous medium. In the…
Efficient and Regioselective One-Pot Synthesis of 3-Substituted and 3,5-Disubstituted Isoxazoles A new one-pot procedure for the synthesis of isoxazoles with reverted…
Palladium-Catalyzed Benzylation of Heterocyclic Aromatic Compounds A method for the palladium-catalyzed benzylation of heterocycles. During the years GalChimia has been carrying…
Microwave-enhanced and Ligand-free Copper-catalyzed Cyanation of Aryl Halides with K4[Fe(CN)6] in Water A microwave-enhanced cyanation in water using an iron-cyanide complex….
General and User-Friendly Protocol for the Synthesis of Functionalized Aryl- and Heteroaryl-cyclopropanes by Negishi Cross-coupling Reactions Introduction of cyclopropyl rings by…
Gold-Catalyzed One-Pot Cascade Construction of Highly Functionalized Pyrrolo[1,2-a]quinolin-1(2H)-ones Synthesis of a fused heterocycle using a gold catalyst. Gold chemistry is one…
Palladium-Catalyzed Synthesis of Diarylmethanes: Exploitation of Carbanionic Leaving Groups An interesting way for the introduction of a methylene bridge between aryl…
Easily Attachable and Detachable ortho-Directing Agent for Arylboronic Acids in Ruthenium-Catalyzed Aromatic C–H Silylation Introduction of diversity in available boronic acids….
Microwave-Assisted trans-Halogenation Reactions of Various Chloro-, Bromo-, Trifluoromethanesulfonyloxy- and Nonafluorobutanesulfonyloxy-Substituted Quinolines, Isoquinolines, and Pyridines Leading to the Corresponding Iodinated Heterocycles A…
C–H Bonds as Ubiquitous Functionalities: A General Approach to Complex Arylated Pyrazoles via Sequential Regioselective C-Arylation and N-Alkylation Enabled by SEM-Group…
Rapid and easy access to indoles via microwave-assisted Hemetsberger–Knittel synthesis A straighforward synthesis of indoles using microwave technology. The synthesis of…
Pd(II)-Catalyzed Olefination of Electron-Deficient Arenes Using 2,6-Dialkylpyridine Ligands An alternative method for meta C–H activation. The introduction of any group in…
Efficient Iron/Copper Co-catalyzed S-Arylations of Thiols with Aryl Halides In the 21st Century, these ancient metals allow fine chemistry. The formation…
Palladium-Catalyzed Direct Arylation of Azine and Azole N-Oxides: Reaction Development, Scope and Applications in Synthesis A demonstration of C–H activation using…
Ruthenium-Catalyzed N-Alkylation of Amines and Sulfonamides Using Borrowing Hydrogen Methodology A powerful alternative to reductive amination using alcohols and a ruthenium…
Iodomesitylene-Catalyzed Oxidative Cleavage of Carbon–Carbon Double and Triple Bonds Using m-Chloroperbenzoic Acid as Terminal Oxidant Oxidative-cleavage of double and triple bonds…
A One-pot Process for the Regioselective Synthesis of 1,3,4-Trisubstituted-1H-pyrazoles A new one-pot procedure for the regioselective preparation of trisubstituted pyrazoles. Pyrazoles…
CuO Nanoparticle-Catalyzed C–N, C–O, and C–S Cross-Coupling Reactions: Scope and Mechanism How nanoparticles can change the way we do catalytic reactions….
Highly Efficient Copper-Catalyzed Cascade Synthesis of Quinazoline and Quinazolinone Derivatives Amidines are useful building blocks for the synthesis of 1,3-diazaheterocycles. See…
Versatile Pd(II)-Catalyzed C–H Activation/Aryl–Aryl Coupling of Benzoic and Phenyl Acetic Acids It is always interesting to see advances being made in…
Indole Synthesis via Rhodium-Catalyzed Oxidative Coupling of Acetanilides and Internal Alkynes A new preparation of 2,3-disubstituted indoles from o-haloanilines and internal…
Synthesis of Condensed Pyrroloindoles via Pd-catalyzed Intramolecular C–H Bond Functionalization of Pyrroles A new method for the preparation of pyrroloindoles via…
Cross-coupling of aryl esters catalyzed by Ni Pivalates are usually considered protecting groups. Change your mind. Transition metal-catalyzed cross-coupling reactions being…
Highly Chemoselective Reductive Amination of Carbonyl Compounds Promoted by InCl3/Et3SiH/MeOH System A new procedure for reductive amination in protic solvents. As…
Palladium- and Nickel-Catalyzed Cross-Couplings of Unsaturated Halides Bearing Relatively Acidic Protons with Organozinc Reagents Zinc can do things that others just…
A General and Efficient Method for the Synthesis of Benzo-(iso)quinoline Derivatives A new method for the preparation of benzoquinolines and benzoisoquinolines….
Cross-Coupling of Cyclopropyl- and Cyclobutyltrifluoroborates with Aryl and Heteroaryl Chlorides The introduction of those small funny cycloalkyls is becoming easier. When…
Direct Acylation of Aryl Bromides with Aldehydes by Palladium Catalysis Preparation of aryl ketones is becoming easier with the new palladium-mediated…
Cu(II)-Catalyzed Direct and Site-Selective Arylation of Indoles under Mild Conditions In previous issues of this newsletter, we have talked about direct…
Copper-Catalyzed Synthesis of Primary Arylamines via Cascade Reactions of Aryl Halides with Amidine Hydrochlorides Sometimes, the fastest way is the shortest…
Pd-Catalyzed Direct Arylation of Tautomerizable Heterocycles with Aryl Boronic Acids via C–OH Bond Activation Using Phosphonium Salts If this method can…
A New Efficient Synthesis of Isothiocyanates from Amines Using di-tert-Butyl Dicarbonate The preparation of many sulfur-containing heterocycles relies on the availability…
An Expeditious and Environmentally Benign Methodology for the Synthesis of Substituted Indoles from Cyclic Enol Ethers and Enol Lactones An interesting…
One-Pot Three-Component Synthesis of Pyrazoles Through a Tandem Coupling-Cyclocondensation Sequence A new method for the one-pot synthesis of pyrazoles from cheap,…
Microwave-Assisted Efficient Copper-Promoted N-Arylation of Amines with Arylboronic Acids The Chan–Lam–Evans reaction is a recent addition to the arsenal of the…
Copper-Catalyzed Domino Annulation Approaches to the Synthesis of Benzoxazoles under Microwave-Accelerated and Conventional Thermal Conditions Sequential one-pot formation of two bonds…
Copper-Mediated Direct Arylation of Benzoazoles with Aryl Iodides From the Far East, here comes another interesting paper about C–H functionalization, in…
Room-Temperature and Phosphine-Free Palladium-Catalyzed Direct C-2 Arylation of Indoles Direct C–H functionalization is an attractive way to increase molecular diversity. A…
Concise Synthesis of 2-Amino-4(3H)-quinazolinones from Simple (Hetero)aromatic Amines Short methods for the preparation of nitrogen heterocycles are always welcome. In this…
Scope of Aminomethylations via Suzuki–Miyaura Cross-Coupling of Organotrifluoroborates Once again, the development of an organometallic cross-coupling reaction increases the array of…
Direct ortho-Cupration: A New Route to Regioselectively Functionalized Aromatics When talking about directed ortho-metallation (DoM), most people think about organolithium bases,…
Meta-Halogenation of 1,3-Disubstituted Arenes via Iridium-Catalyzed Arene Borylation Preparation of aryl halides is a key step in many syntheses, but the…
Convergent Synthesis of Polysubstituted Aromatic Nitriles via Palladium-Catalyzed C–H Functionalization Metal-mediated alkylations and cyanations are not new but, what about accomplishing…
