Feng Group

Publications

Prior to UF:

7. Development of a deactivation-resistant dialkylbiarylphosphine ligand for Pd-catalyzed arylation of secondary amines
Feng, K.†; Raguram, E. R.†; Howard, J. R.; Peters, E.; Liu, C.; Sigman, M. S.; Buchwald, S. L.
J. Am. Chem. Soc. 2024, 146, 26609

A chemical reaction scheme showing a palladium-catalyzed C–N coupling between a heteroaryl halide (Het–X, where X = Cl, Br, or I) and a secondary amine (R–NH–R′). The reaction uses Pd/FPhos (0.5–3.0 mol%), NaOt-Bu (1.05 equiv), in 1,4-dioxane at 60–85 °C for 1–6 hours, yielding a heteroaryl amine (Het–NRR′). The figure notes ‘25 examples, average 88% yield.’ Below, a panel of various nitrogen-containing heterocycles indicates substrate scope, labeled ‘Accommodates coordinating N-heteroarenes.’ On the right, a mechanistic inset depicts an O-bound palladium oxidative addition complex with a bulky phosphine ligand (Pcyp₂) and aryl group, highlighting 3′,5′-disubstitution and CF₃ groups influencing the structure.

6. Pd-catalyzed amination of base-sensitive five-membered heteroaryl halides with aliphatic amines
Reichert, E. C.†; Feng, K.†; Sather, A. C.; Buchwald, S. L.
J. Am. Chem. Soc. 2023, 145, 3323

Scientific scheme depicting a palladium-catalyzed C–H amination of base-sensitive heteroaryl halides with aliphatic secondary amines. Top left (blue box): Three representative base-sensitive heteroaryl halide substrates are shown — a methylimidazole, a methylthiazole, and a triazole — each bearing a halide (X) and an acidic C–H bond (highlighted in red), illustrating the sensitivity challenge. Center (reaction scheme): The general reaction combines a heteroaryl halide (Het, X = Cl, Br, or I) with an aliphatic secondary amine (NHR R') under the following conditions: Pd-GPhos (1.5–5 mol%) as palladium catalyst NaOTMS (1.05 equiv) as base THF (0.4 M), 50–90 °C, 3 hours Bottom left: The amine scope is illustrated with several structural classes of aliphatic secondary amines, including pyrrolidines (n = 0–3), acyclic amines (NHR R'), and piperazines/morpholines (n = 0–1). Right side (green box): A complex drug-like molecule bearing a pyrazole, ethyl ester, spiro-oxazine, and lactam is shown as an example product, highlighting broad functional group compatibility. Results summary: 33 examples, average 86% yield.

5. The quest for magic: recent advances in C(sp3)–H methylation
Feng, K.
Pure Appl. Chem. 2022, 94, 547

4. Late-stage intermolecular allylic C–H amination
Ide, T.; Feng, K.†; Dixon, C. F.†; Teng, D.†; Clark, J. R.; Han, W.; Wendell, C. I.; Koch, V.; White, M. C.
J. Am. Chem. Soc. 2021, 143, 14969

Scientific figure showcasing a late-stage C–H amination of a complex natural product. Top left: The starting material is TBS-Brefeldin A (an antifungal and antimitotic natural product), with two allylic C–H bonds labeled Hₐ and H_b highlighted in red and blue respectively. Center (reaction arrow): Conditions shown are [Mn³(ClPc)SbF₆] as catalyst, PhI=NTces as the nitrogen source, 55% yield, with complete selectivity for 1 regioisomer and 1 stereoisomer. Top right: The amination product is shown, with the newly installed NHTces group (highlighted in yellow) installed selectively at the H_b position on the macrocyclic framework, with atom numbering and TBS protecting groups retained. Bottom left: A blue-bordered box highlights the [Mn³(ClPc)SbF₆] catalyst — a manganese chlorophthalocyanine complex — described as a "commercial, sustainable catalyst," with its structure drawn showing the phthalocyanine ligand bearing multiple chlorine substituents. Bottom right: An X-ray crystal structure of the amination product is shown as an ORTEP-style thermal ellipsoid plot, confirming the assigned regio- and stereochemistry. Key bullet points note: 32 examples, high selectivity, and high functional group tolerance.

3. Late-stage oxidative C(sp3)–H methylation
Feng, K.†; Quevedo, R. E.†; Kohrt, J. T.; Oderinde, M.; Reilly, U.; White, M. C.
Nature 2020, 580, 621

Scientific scheme illustrating a late-stage oxidative methylation reaction using Mn(CF₃PDP) oxidation followed by AlMe₃ methylation. A small ball-and-stick model in the upper right depicts a methyl group (Me) being installed. The main panel (shaded gray) displays 12 substrate structures demonstrating the broad scope of the transformation, with the newly installed methyl groups highlighted in yellow and labeled in blue. Substrates include a diverse array of nitrogen-containing heterocycles and carbocycles: pyrrolidinones (n=1,2), oxazolidinones, pyrrolidines (n=1–3), bridged bicyclic amines, piperidine sulfonamides, a benzofuran, an isoindolinone, a chromane, tetrahydroisoquinolines, a decalin, a cyclohexane, and a linear amine bearing an NHPh group. The caption reads: "Late-Stage Oxidative Methylation: 14 heterocycles, 1 carbocycle, 1 linear amine."

An artistic, tree-like visualization of chemical structures on a dark background. A bright central trunk branches into three glowing pathways (green, pink, and white), each leading to clusters of ball-and-stick molecular models. Additional molecular structures are scattered throughout the background like constellations. The image illustrates late-stage C(sp3)–H methylation.

2. Manganese-catalysed benzylic C(sp3)–H amination for late-stage functionalization
Clark, J. R.; Feng, K.†; Sookezian, A.†; White, M. C.
Nat. Chem. 2018, 10, 583

Scientific reaction scheme illustrating a C–H amination reaction catalyzed by a manganese porphyrin complex. On the left, a generic styrene substrate (ArCH=CH₂, with substituents R and R¹) is shown as the starting material. In the center, a large green sphere represents the catalyst — a manganese(III) porphyrin bearing eight chlorine substituents on the porphyrin ring, with SbF₆⁻ as the counterion. Arrows radiate outward to five product examples on the right, each bearing an NHTces (trichloroethylsulfonyl-protected amine) group highlighted in yellow, demonstrating the broad substrate scope: more hindered, less hindered, basic amine, electron-rich, and electron-poor substrates. A summary in the lower left notes 43 examples with 61% average yield.

Nature Chemistry Journal Cover — June 2018, Vol. 10 No. 6 Cover of Nature Chemistry magazine featuring a dark blue background with illustrated molecular structures. A glowing chemical reaction is depicted at the center, showing a transformation between molecules — a teal/cyan nitrogen-containing compound on the left reacting with a gold/orange aromatic molecule on the right, connected by a bright white energy flash above a green catalyst surface. The headline reads "Advancing amination." The Nature Chemistry masthead appears in white and green at the top. Three article teasers are listed at the bottom: "DNA Structures — I-motifs identified," "Molecular Machines — Shuttling through and through," and "Heterogeneous Catalysis — Cooperative communication.

1. Remote oxidation of aliphatic C–H bonds in nitrogen-containing molecules
Howell, J. M.†; Feng, K.†; Clark, J. R.; Trzepkowski, L. J.; White, M. C.
J. Am. Chem. Soc. 2015, 137, 14590

A chemical reaction scheme illustrating a remote C–H oxidation on a complex steroid-like molecule. The starting structure contains a fused polycyclic framework with methyl (Me) groups and an acetate (AcO) substituent, along with a heteroaromatic ring. A highlighted hydrogen atom (in red) marks the site of oxidation. The reaction uses Fe(PDP) or Fe(CF₃PDP) catalysts to achieve selective oxidation, depicted via an intermediate involving a protonated heterocycle (Het–H⁺, with BF₄⁻ counterion). The product shows conversion of the highlighted C–H bond into a C–OH group (highlighted in yellow). The figure notes substrate scope (‘Het = piperidine, pyridine; amine (1°, 2°, 3°), imide (direct oxidation)’) and reports ‘39 examples, avg. 53% yield.’

Patents

1. Manganese (III) catalyzed C–H aminations
White, M. C.; Clark, J. R.; Feng, K.; Sookezian, A.; Wendell, C.
U.S. Patent, 2020, US 10,611,786 B2