Direct Sp3 Research Articles

ChemInform Abstract: Bi(OTf)3‐Catalyzed C—H Bond Functionalization of Azaarenes for the Facile Access to Oxindoles Featuring Quaternary Carbon Centers.

The direct sp3 C–H bond functionalization of 2-alkyl azaarenes to isatylidene malononitriles has been achieved using Bi(OTf)3 as the catalyst, resulting in a series of oxindoles containing an all-carbon quaternary center in moderate to good yields. This protocol provided an efficient and convenient method for the construction of potentially useful azaarene substituted oxindoles.

Photochemically-induced C-C bond formation between tertiary amines and nitrones.

Photoexcited nitrones serve as excellent electron acceptors as well as radical acceptors in the presence of tertiary amines to give β-amino hydroxylamines via photochemically-induced direct sp(3) C-H functionalization of the tertiary amines. The combined use of an organophotosensitizer and photoirradiation was highly effective in accelerating addition reactions. Several nitrones and tertiary amines were successfully utilized to give β-amino hydroxylamines in good yield. Highly regioselective generation of primary α-aminoalkyl radicals based on Lewis's stereoelectronic rule and diastereoselective addition reactions of primary α-aminoalkyl radicals with nitrones were successfully achieved. Furthermore, a highly diastereoselective reaction of an α-aminoalkyl radical with a chiral (E)-geometry-fixed α-alkoxycarbonylnitrone was performed.

Palladium-Catalyzed Direct α-Aryation of Benzyl Thioethers with Aryl Bromides.

The arylation of sp3-hybridized C-H's bonds is a powerful strategy to build molecular complexity and diversity. A novel and efficient palladium-catalyzed direct sp3 C-H arylation of aryl and alkyl benzyl thioether derivatives with aryl bromides is reported. The reaction involves reversible deprotonation of the benzylic C-H's of the thioether with either LiN(SiMe3)2 or NaN(SiMe3)2 and subsequent cross-coupling to provide the functionalized products in up to 97% yield. A screen of 24 of the most successful ligands in cross-coupling chemistry led to the identification of NiXantPhos as the only viable ligand for this challenging coupling.

ChemInform Abstract: Metal‐ and Oxidant‐Free Direct sp3 C—H Arylation of Pyrrolidine.

AbstractThis is an operationally simple and highly atom economic three‐component reaction for the direct sp3 C—H arylation of pyrrolidine.

Direct sp3 C–H acroleination of N-aryl-tetrahydroisoquinolines by merging photoredox catalysis with nucleophilic catalysis

Sequence catalysis merging photoredox catalysis (PC) and nucleophilic catalysis (NC) has been realized for the direct sp(3) C-H acroleination of N-aryl-tetrahydroisoquinoline (THIQ). The reaction was performed under very mild conditions and afforded products in 50-91% yields. A catalytic asymmetric variant was proved to be successful with moderate enantioselectivities (up to 83 : 17 er).

Metal‐ and Oxidant‐Free Direct sp3 CH Arylation of Pyrrolidine

AbstractArylated aliphatic N‐heterocycles, and particularly arylated pyrrolidines, have a wide range of applications in medicine as well as in chemistry. Arylation of pyrrolidines mainly relies on metal‐mediated couplings, which produce unwanted toxic metal waste. In this Communication, we report an oxidant‐ and metal‐free method for direct sp3 CH arylation of pyrrolidine employing a highly atom economic three‐component reaction. The method, operating under very simple and mild conditions, is highly selective and very efficient in producing single regioisomer of the arylated product even on a multigram scale. As an alternative to the metal‐mediated reaction, this method has the potential to be used in production at an industrial scale. Moreover, a new approach for CH arylation based on a novel reactivity that differs from the reactivity in Mannich or Betti reactions of iminium ion is presented.

Mechanistic investigations and substrate scope evaluation of ruthenium-catalyzed direct sp3 arylation of benzylic positions directed by 3-substituted pyridines.

A highly efficient direct arylation process of benzylic amines with arylboronates was developed that employs Ru catalysis. The arylation takes place with greatest efficiency at the benzylic sp3 carbon. If the distance to the activating aryl ring is increased, arylation is still possible but the yield drops significantly. Efficiency of the CH activation was found to be significantly increased by use of 3-substituted pyridines as directing groups, which can be removed after the transformation in high yield. Calculation of the energy profile of different rotamers of the substrate revealed that presence of a substituent in the 3-position favors a conformation with the CH2 group adopting a position in closer proximity to the directing group and facilitating C–H insertion. This operationally simple reaction can be carried out in argon atmosphere as well as in air and under neutral reaction conditions, displaying a remarkable functional group tolerance. Mechanistic studies were carried out and critically compared to mechanistic reports of related transformations.

Metal-free oxidative hydroxyalkylarylation of activated alkenes by direct sp3 C–H functionalization of alcohols

A metal-free tandem radical addition/cyclization reaction of activated alkenes and alcohols has been developed. The process provides an efficient and atom economical access to various valuable hydroxyl-containing oxindoles through the direct sp(3) C-H functionalization of alcohols.

Palladium-Catalyzed Direct Benzylation of Azoles with Benzyl Carbonates

The direct aromatic sp(2) C-H benzylation of azole compounds with benzyl carbonates proceeds efficiently in the presence of a Pd(2)(dba)(3)/dppp catalyst system and NaOAc as a base to afford the corresponding diarylmethanes in good yields. In addition, the same palladium catalyst enables the direct benzylic sp(3) C-H benzylation with the second benzyl carbonates without employing any external base.

Oxidative Cyanation of Tertiary Amines

A novel Ru-catalyzed oxidative cyanation of tertiary amines with molecular oxygen or hydrogen peroxide is described. The reaction proceeds via a direct sp³ C-H bond activation α to the nitrogen mediated by the Ru complex. Oxidation leads to an iminium ion and Ru hydroperoxide. Reaction with HCN gives the desired α-aminonitriles.

Ruthenium-Catalyzed Oxidative Cyanation of Tertiary Amines with Molecular Oxygen or Hydrogen Peroxide and Sodium Cyanide: sp3 C−H Bond Activation and Carbon−Carbon Bond Formation

Ruthenium-catalyzed oxidative cyanation of tertiary amines with molecular oxygen in the presence of sodium cyanide and acetic acid gives the corresponding alpha-aminonitriles, which are highly useful intermediates for organic synthesis. The reaction is the first demonstration of direct sp(3) C-H bond activation alpha to nitrogen followed by carbon-carbon bond formation under aerobic oxidation conditions. The catalytic oxidation seems to proceed by (i) alpha-C-H activation of tertiary amines by the ruthenium catalyst to give an iminium ion/ruthenium hydride intermediate, (ii) reaction with molecular oxygen to give an iminium ion/ruthenium hydroperoxide, (iii) reaction with HCN to give the alpha-aminonitrile product, H2O2, and Ru species, (iv) generation of oxoruthenium species from the reaction of Ru species with H2O2, and (v) reaction of oxoruthenium species with tertiary amines to give alpha-aminonitriles. On the basis of the last two pathways, a new type of ruthenium-catalyzed oxidative cyanation of tertiary amines with H2O2 to give alpha-aminonitriles was established. The alpha-aminonitriles thus obtained can be readily converted to alpha-amino acids, diamines, and various nitrogen-containing heterocyclic compounds.

Sp3 C−H Bond Arylation Directed by Amidine Protecting Group: α-Arylation of Pyrrolidines and Piperidines

A new ruthenium-catalyzed direct sp3 C-H to C-C bond transformation is disclosed. Specifically, a method for the alpha-arylation of cyclic amines, containing either permanent (pyridine, pyrimidine) or removable (amidine) directing groups, is described. This cross-coupling reaction involves heating amine substrates with arylboronate ester at 150 degrees C in a ketone solvent with a catalytic amount of ruthenium carbonyl [Ru3(CO)12]. Arylboronate esters containing either electron-withdrawing or electron-donating substituents could be efficiently coupled. Heteroarene boronates were also effective donors.

Oxidative C-Arylation of Free (NH)-Heterocycles via Direct (sp3) C−H Bond Functionalization [J. Am. Chem. Soc. 2004, 126, 13244−13246

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTADDITION / CORRECTIONThis article has been corrected. View the notice.Oxidative C-Arylation of Free (NH)-Heterocycles via Direct (sp3) C−H Bond Functionalization [J. Am. Chem. Soc.2004, 126, 13244−13246].Bengü Sezen and Dalibor SamesCite this: J. Am. Chem. Soc. 2006, 128, 9, 3102Publication Date (Web):March 1, 2006Publication History Published online1 March 2006Published inissue 1 March 2006https://doi.org/10.1021/ja069957dCopyright © 2006 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views2348Altmetric-Citations1LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (12 KB) Get e-Alerts Get e-Alerts