Copper-catalyzed Transformation Research Articles

Copper-Catalyzed Difunctionalization of Propargylic Carbonates through Tandem Nucleophilic Substitution/Boroprotonation.

Highly functionalized organic molecules are in high demand, but their preparation is challenging. Copper-catalyzed transformation of alkynyl- and allenyl-containing substrates has emerged as a powerful tool to achieve this objective. Herein, an efficient copper-catalyzed difunctionalization of propargylic carbonates through tandem nucleophilic substitution/boroprotonation has been developed, affording the formation of thiol-, selenium-, and boron-functionalized alkenes with high yield and stereoselectivity. Two distinct catalytic mechanisms involving a single reaction without any requirement of catalyst change were successfully demonstrated.

Copper-catalyzed strain-enabled reaction of bicyclobutanes with diazo compounds to synthesize penta-1,4-dienes.

Herein we report an interesting copper-catalyzed transformation of BCBs with diazo compounds. This reaction leads to the synthesis of substituted skipped penta-1,4-dienes in good to excellent yields with only one diastomer obtained, and the reaction can also be performed on a gram scale. The transformation is compatible with many different functional groups attached to the BCBs and the diazo compounds.

Copper-Catalyzed Synthesis of Difluoromethyl Alkynes from Terminal and Silyl Acetylenes.

An efficient method for the direct C(sp)-H difluoromethylation of terminal alkynes and the desilylation-difluoromethylation of (trimethylsilyl)acetylenes is disclosed. The copper-catalyzed transformation provides access to a wide range of structurally diverse CF2H alkynes in good yields, utilizing a (difluoromethyl)zinc reagent and an organic oxidant. The difluoromethylation of important synthons and API's is showcased. The synthetic utility of these (difluoromethyl)alkynes is demonstrated by selected cycloaddition reactions. Additionally, a slight modification to the reaction conditions allowed the selective preparation of a 2-difluoromethylindole.

Cu-Catalyzed Three-Component Cascade Synthesis of 1,3-Benzothiazines from ortho-Aminohydrazones and Bromodifluoroacetamides.

An efficient and convenient synthesis of benzo[d][1,3]thiazine has been developed by employing a copper-catalyzed transformation of readily available ketone-derived hydrazones with elemental sulfur and bromodifluoroalkylative reagents. The strategy involves an S8-catalyzed selective triple-cleavage of bromodifluoroacetamides, which acts as a C1 synthon at the 2-position of benzo[d][1,3]thiazine. A mechanism proceeding through a Cu-carbene intermediate is proposed for the C-S bond formation.

Copper-Catalyzed Chemoselective Silylative Cyclization of 2,2'-Diethynylbiaryl Derivatives.

In this protocol, copper-catalyzed diverse silylative carbocyclization reactions of 2,2'-diethynylbiaryl derivatives with silaboronate were reported. Three new and novel types of domino reactions for the copper-catalyzed transformation of silaboronate were discovered. The corresponding cyclobuta[l]phenanthrene, bis((silyl)methyl)phenanthrene, and silyl-substituted exocyclic diene products were chemoselectively formed with high efficiency.

Late-Stage Transformation of Carboxylic Acids to N-Trifluoroethyl­imides with Trifluoromethyl Diazomethane

AbstractWe report the first systematic evaluation of the reaction of trifluoromethyl diazomethane (2,2,2-trifluorodiazoethane, CF3CHN2) with drug-like molecules. We found our previous copper-catalyzed transformation of carboxylic acids to the corresponding N-trifluoro­ethylimides with CF3CHN2 and acetonitrile is well-suited for the late-stage modification of drug and drug-like acids. A procedure that enables the use of solid nitriles and nitriles with high boiling points as viable substrates is also disclosed.

Divergent Synthesis of Disulfanes and Benzenesulfonothioates Bearing 2-Aminofurans From N-Tosylhydrazone-Bearing Thiocarbamates.

An efficient and convenient synthesis of valuable disulfanes and benzenesulfonothioates, having a 2-aminofuran framework, has been developed by employing a copper-catalyzed transformation of readily available N-tosylhydrazone-bearing thiocarbamates. This method features an inexpensive metal catalyst, mild reaction conditions, good functional-group tolerance, short reaction times, and delivers valuable and complex products. A copper carbene generated from an N-tosylhydrazone-bearing thiocarbamate is proposed as the key intermediate for the transformation and it triggers the subsequent cascade. Remarkably, the Ts anion released from N-tosylhydrazone further serves as a nucleophile, thus rendering the formation of benzenesulfonothioates under controlled conditions.

Copper-catalyzed transformation of ketones to amides via C(CO)-C(alkyl) bond cleavage directed by picolinamide.

Copper catalyzed chemoselective cleavage of the C(CO)-C(alkyl) bond leading to C-N bond formation with chelation assistance of N-containing directing groups is described. Inexpensive Cu(ii)-acetate serves as a convenient catalyst for this transformation. This method highlights the emerging strategy to transform unactivated alkyl ketones into amides in organic synthesis and provides a new strategy for C-C bond cleavage.

Copper-Catalyzed Transformation of Hydrazones into Halogenated Azabutadienes, Versatile Building Blocks for Organic Synthesis

A one-step copper-catalyzed reaction of aldehyde-derived N-substituted hydrazones with CCl4 resulted in efficient synthesis of 4,4-dichloro-1,2-diazabuta-1,3-dienes. It was proven that this C–C bond-forming cascade reaction operates via an addition of trichloromethyl radical to the C═N bond of hydrazone followed by a base-induced elimination of HCl. The reaction was found to be very general, as diverse hydrazones possessing various aromatic groups at N-site, as well as aromatic, aliphatic, and heterocyclic substituents at C-site, are capable partners for coupling with a wide range of polyhalogenated compounds (CCl3Br, CBr4, CCl3CN, CCl3COOEt, CCl3CF3, CBr3CF3) to produce a family of functionalized 1,2-diazabuta-1,3-dienes. It was demonstrated that the prepared heterodienes are highly versatile building blocks for straightforward assembly of various valuable acyclic and heterocyclic molecules.

ChemInform Abstract: Copper‐Catalyzed Oxidative Transformation of Secondary Alcohols to 1,5‐Disubstituted Tetrazoles.

AbstractA mild and convenient protocol using TmsN3 as a nitrogen source is developed for the conversion of cinnamyl and benzyl alcohols into disubstituted tetrazoles.

Chemoselective Oxidative C(CO)C(methyl) Bond Cleavage of Methyl Ketones to Aldehydes Catalyzed by CuI with Molecular Oxygen

Aldehyde Termination: A novel copper-catalyzed transformation from methyl ketones into aldehydes has been accomplished. This method is applicable to a wide range of aromatic and aliphatic methyl ketones and chemoselectively produces aldehydes, accompanied by the release of hydrogen (H2 ) and carbon dioxide (CO2 ) as by-products.

A copper-catalyzed, pH-neutral construction of high-enantiopurity peptidyl ketones from peptidic s-acylthiosalicylamides in air at room temperature.

A copper-catalyzed transformation of peptidic thiol esters and boronic acids gives peptidyl ketones and takes place in DMF or DMF/H(2)O at room temperature in air (see scheme). This aerobic reaction only occurs at a thiol ester group capable of coordinating to Cu through its appendage on the sulfur center and is not hampered by racemization of the reactants or products.

Copper-catalyzed transformation of carbonyl-ene-nitrile compounds: Vinylation, imino ene reaction, and alkynylation of 2-aza-2,4-cyclopentadienone intermediates generated via Ritter-type hydration and dehydrative cyclization reactions

1 H-pyrrolin-2(5 H)-one derivatives are easily obtained from carbonyl-ene-nitrile compounds and alkenes or alkynes by copper(II)-catalyzed tandem sequence involving vinylation or allylation as well as Ritter-type hydration and dehydrative cyclization.