C–H Functionalization
C–H Functionalization has the potential to become a paradigmshifting strategy for organic synthesis. Over the last decade, the field has experienced explosive growth and a large variety of new C–H functionalization methodologies have been developed. In particular, regioselective functionalization of sp2 C–H bonds has become a broadly flexible approach for the synthesis of complex aromatic carbocycles and heterocycles. The selective functionalization of sp3C–H bonds is a more challenging proposition, but in recent years significant advances have been made to suggest that even these types of transformations can become broadly applicable. This Thematic Series highlights some of the novel approaches that are applied to the field of C–H functionalization and it covers topics that range from novel catalyst design, new synthetic methods, and cascade sequences that incorporate C–H functionalization.
See also the Thematic Series:
C–H Functionalization/activation in organic synthesis
- Letter
- Published 14 Sep 2012
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Scheme 1: (a) Cobalt-catalyzed C2-alkenylation of N-pyrimidylindole, (b) ortho-alkylation of aryl imine, and ...
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Scheme 2: Addition of N-pyrimidylindoles to vinylsilanes.
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Scheme 3: Addition of N-pyrimidylindole to norbornene (a) and 1-octene (b).
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Scheme 4: Gram-scale reaction and deprotection of N-pyrimidyl group.
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- Review
- Published 18 Sep 2012
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Scheme 1: Heterolytic cleavage of H2 by a phosphine/borane FLP by H2 polarization in the P–B cavity [5,11].
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Scheme 2: Insertion of carbon dioxide into a phosphine/borane FLP [14].
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Figure 1: Simplified frontier-molecular-orbital diagrams for (a) Mδ+═Eδ− and (b) Mδ−═Eδ+ FLPs (n = 1 for line...
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Figure 2: Quenching of M═E FLPs by dimerization: (a) generic Mδ+═Eδ− case, and (b) Bergman's arylimido zircon...
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Scheme 3: Oxygen-atom extrusion from CO2 by a Ta(V) neopentylidene [27].
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Scheme 4: Oxygen-atom transfer from acetone at a Zr(IV) imide [28].
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Scheme 5: Alkyne cycloaddition at a Zr(IV) imide [38].
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Scheme 6: Nitrile-alkyne cross metathesis at a W(VI) nitride [40,41].
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Scheme 7: C–H and H–H addition across a zirconium(IV) imide [42].
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Scheme 8: Formal [2 + 2] cycloaddition of methyl isocyanate at a ruthenium silylene [58].
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Scheme 9: Oxygen-atom transfer from phenyl isocyanate to a cationic terminal borylene [60].
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Scheme 10: Coupling of a phosphorus ylide with an iridium methylene [62].
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Scheme 11: Reactions of (PNP)Ir═C(H)Ot-Bu with oxygen-containing heterocumulenes [71].
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Scheme 12: Reductive coupling of two CS2 units at (PNP)Ir═C(H)Ot-Bu [73].
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Figure 3: Single-crystal X-ray structure of a silver(I) triflate adduct of (PNP)Ir═C(H)Ot-Bu with most H atom...
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Scheme 13: Possible routes to C–H functionalization by 1,2-addition across a polarized metal–element multiple ...
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Scheme 14: Alkoxycarbene formation by double C–H activation at (PNP)Ir [88].
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Scheme 15: Catalytic oxidation of MTBE by multiple C–H activations and nitrene-group transfer to a Mδ−═Eδ+ FLP ...
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- Letter
- Published 18 Sep 2012
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Scheme 1: Synthesis of arylglycine derivatives.
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Scheme 2: Oxidative sp3 C–H functionalization of α-amino esters.
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Scheme 3: Proposed mechanism.
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- Full Research Paper
- Published 18 Sep 2012
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Scheme 1: Synthesis of methyl (1H)-isoindolin-1-one-3-carboxylates by carbonylation of phenylglycine derivati...
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Scheme 2: Synthesis and NMR characterization of orthometallated complex 3.
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Scheme 3: Carbonylation of 1 to afford glutamate and glutamine derivatives 2a–j.
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Figure 1: Scope of the carbonylation reaction.
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Scheme 4: Reaction of 1 and CO in CH2Cl2 [18].
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Scheme 5: Reactivity of 3 with CO in the presence (left) and absence (right) of nucleophiles.
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- Full Research Paper
- Published 27 Sep 2012
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Figure 1: [Pd(NHC)(cin)Cl] catalysts examined in direct arylation.
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Scheme 1: Synthesis of [Pd(IPr*Tol)(cin)Cl] (4).
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Figure 2: Molecular structure of 4. H atoms were omitted for clarity. Selected bond lengths (Å) and angles (°...
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Figure 3: Previously reported catalytic systems in the direct arylation of benzothiophene (6).
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- Review
- Published 11 Oct 2012
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Scheme 1: Typical catalytic cycle for Pd(II)-catalyzed alkenylation of indoles.
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Scheme 2: Application of Fujiwara’s reaction to electron-rich heterocycles.
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Scheme 3: Regioselective alkenylation of the unprotected indole.
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Scheme 4: Plausible mechanism of the selective indole alkenylation, adapted from [49].
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Scheme 5: Directing-group control in intermolecular indole alkenylation.
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Scheme 6: Direct C–H alkenylation of N-(2-pyridyl)sulfonylindole.
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Scheme 7: N-Prenylation of indoles with 2-methyl-2-butene.
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Scheme 8: Proposed mechanism of the N-indolyl prenylation.
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Scheme 9: Regioselective arylation of indoles by dual C–H functionalization.
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Scheme 10: Plausible mechanism of the selective indole arylation.
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Scheme 11: Chemoselective cyclization of N-allyl-1H-indole-2-carboxamide derivatives.
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Scheme 12: Intramolecular annulations of alkenylindoles.
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Scheme 13: A mechanistic probe for intramolecular annulations of alkenylindoles, adapted from Ferreira et al. [66]....
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Scheme 14: Asymmetric indole annulations catalyzed by chiral Pd(II) complexes.
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Scheme 15: Aerobic Pd(II)-catalyzed endo cyclization and subsequent amide cleavage/ester formation.
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Scheme 16: Synthesis of the pyrimido[3,4-a]indole skeleton by intramolecular C-2 alkenylation.
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Scheme 17: Synthesis of azepinoindoles by oxidative Heck cyclization.
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Scheme 18: Enantioselective synthesis of 4-vinyl-substituted tetrahydro-β-carbolines.
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Scheme 19: Pd-catalyzed endo-cyclization of 3-alkenylindoles for the construction of carbazoles.
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Scheme 20: Pd-catalyzed hydroamination of 2-indolyl allenamides.
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Scheme 21: Amidation reaction of 1-allyl-2-indolecarboxamides.
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Scheme 22: Intramolecular cyclization of N-benzoylindole.
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Scheme 23: Intramolecular alkenylation/carboxylation of alkenylindoles.
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Scheme 24: Intermolecular alkenylation/carboxylation of 2-substituted indoles.
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Scheme 25: Mechanistic investigation of the cyclization/carboxylation reaction.
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Scheme 26: Plausible catalytic cycle for the cyclization/carboxylation of alkenylindoles, adapted from Liu et ...
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Scheme 27: Intramolecular domino reactions of indolylallylamides through alkenylation/halogenation or alkenyla...
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Scheme 28: Proposed mechanism for the alkenylation/esterification process through iminium intermediates.
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Scheme 29: Cyclization of 3-indolylallylcarboxamides involving 1,2-migration of the acyl group from spiro-inte...
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Scheme 30: Domino reactions of 2-indolylallylcarboxamides involving N–H functionalization.
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Scheme 31: Cyclization/acyloxylation reaction of 3-alkenylindoles.
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Scheme 32: Doubly intramolecular C–H functionalization of a 2-indolylcarboxamide bearing two allylic groups.
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Copper-catalyzed CuAAC/intramolecular C–H arylation sequence: Synthesis of annulated 1,2,3-triazoles
- Full Research Paper
- Published 16 Oct 2012
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Scheme 1: Copper-catalyzed step-economical C–H arylation-based cascade reaction.
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Scheme 2: Copper-catalyzed sequential catalysis with alkyne 1a.
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Scheme 3: Copper-catalyzed reaction sequence using alkyl bromides 2. General reaction conditions: 1 (1.00 mmo...
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Scheme 4: Nonsequential cascade synthesis of fully substituted triazoles 4. General reaction conditions: 1 (1...
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Scheme 5: Copper-catalyzed one-pot twofold C–H/N–H arylation with azoles 5. aReaction performed at 120 °C.
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- Letter
- Published 29 Oct 2012
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Figure 1: The ORTEP drawing of 3c with 30% probability ellipsoids, and Flack absolute structure parameter of ...
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- Full Research Paper
- Published 05 Feb 2013
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Scheme 1: Hydroarylation of alkynes.
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Figure 1: Gold(I) and gold(III) NHC complexes employed as catalysts in this study.
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Scheme 2: Hydroarylation of ethyl propiolate with pentamethylbenzene.
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Figure 2: Yield in 3{1,1} versus time diagram for the reaction of pentamethylbenzene and ethyl propiolate cat...
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Scheme 3: Hydroarylation experiment with catalyst VI under neutral conditions.
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Scheme 4: Intramolecular cyclisation through hydroarylation investigated in this work.
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- Full Research Paper
- Published 20 Mar 2013
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Figure 1: Stationary points located along the reaction path of the aromatic hydroxylation mechanism (some H a...
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Figure 2: Computed structures of the potential equilibrium between the peroxo and bis-μ-oxo intermediates (so...
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Figure 3: Computed structures for a potential alternative pathway f→g of the σ* mechanism (some H atoms omitt...
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Figure 4: Computed structures for a potential alternative pathway e→g of the σ* mechanism (some H atoms omitt...
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Figure 5: Computed structures for a potential alternative pathway j→i of the σ* mechanism (Gibbs energies in ...
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Figure 6: Computed structures for a potential alternative pathway b→g of the σ* mechanism (some H atoms omitt...
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Figure 7: Computed structures for a potential alternative pathway c→g of the σ* mechanism (some H atoms omitt...
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