Iron Catalyzed Asymmetric Oxyamination of Olefins

The regioselective and enantioselective oxyamination of alkenes with <i>N</i>-sulfonyl oxaziridines is catalyzed by a novel iron­(II) bis­(oxazoline) complex. This process affords oxazolidine products that can be easily manipulated to yield highly enantioenriched free amino alcohols. The regioselectivity of this process is complementary to that obtained from the analogous copper­(II)-catalyzed reaction. Thus, both regioisomers of enantioenriched 1,2-aminoalcohols can be obtained using oxaziridine-mediated oxyamination reactions, and the overall sense of regiochemistry can be controlled using the appropriate choice of inexpensive first-row transition metal catalyst

Photocatalytic Indole Diels–Alder Cycloadditions Mediated by Heterogeneous Platinum-Modified Titanium Dioxide

Indole alkaloids represent an important class of molecules, with many naturally occurring derivatives possessing significant biological activity. One area that requires further development in the synthesis of indole derivatives is the Diels–Alder reaction. In this work, we expand on our previously developed heterogeneous protocol for the [4 + 2] cycloaddition of indoles and electron-rich dienes mediated by platinum nanoparticles supported on titanium dioxide semiconductor particles (Pt(0.2%)@TiO₂) with visible-light irradiation. This reaction proceeds with broad scope and is more efficient per incident photon than the previous homogeneous method, and the catalyst can be easily recycled and reused

Transition Metal Photoredox Catalysis of Radical Thiol-Ene Reactions

We describe the anti-Markovnikov hydrothiolation of olefins using visible-light-absorbing transition metal photocatalysts. The key thiyl radical intermediates are generated upon quenching of photoexcited Ru*­(bpz)₃² with a variety of thiols. The adducts of a wide variety of olefins and thiols are formed in excellent yield (73–99%)

Enantioselective Photocatalytic [3 + 2] Cycloadditions of Aryl Cyclopropyl Ketones

Control of stereochemistry in photocycloaddition reactions remains a substantial challenge; almost all successful catalytic examples to date have involved [2 + 2] photocycloadditions of enones. We report a method for the asymmetric [3 + 2] photocycloaddition of aryl cyclopropyl ketones that enables the enantiocontrolled construction of densely substituted cyclopentane structures not synthetically accessible using other catalytic methods. These results show that the dual-catalyst strategy developed in our laboratory broadens synthetic chemists’ access to classes of photochemical cycloadditions that have not previously been feasible in enantioselective form

Redox Mediators in Visible Light Photocatalysis: Photocatalytic Radical Thiol–Ene Additions

Synthetically useful radical thiol–ene reactions can be initiated by visible light irradiation in the presence of transition metal polypyridyl photocatalysts. The success of this method relies upon the use of <i>p</i>-toluidine as an essential additive. Using these conditions, high-yielding thiol–ene reactions of cysteine-containing biomolecules can be accomplished using biocompatibile wavelengths of visible light, under aqueous conditions, and with the thiol component as the limiting reagent. We present evidence that <i>p</i>-toluidine serves as a redox mediator that is capable of catalyzing the otherwise inefficient photooxidation of thiols to the key thiyl radical intermediate. Thus, we show that co-catalytic oxidants can be important in the design of synthetic reactions involving visible light photoredox catalysis

Brønsted Acid Cocatalysts in Photocatalytic Radical Addition of α‑Amino C–H Bonds across Michael Acceptors

In marked contrast to the variety of strategies available for oxidation and nucleophilic functionalization of methylene groups adjacent to amines, relatively few approaches for modification of this position with electrophilic reaction partners have been reported. In the course of an investigation of the reactions of photogenerated α-amino radicals with electrophiles, we made the surprising observation that the efficiency of radical photoredox functionalization of <i>N</i>-aryl tetrahydroisoquinolines is dramatically increased in the presence of a Brønsted acid cocatalyst. Optimized conditions provide high yields and efficient conversion to radical addition products for a range of structurally modified tetrahydroisoquinolines and enones using convenient household light sources and commercially available Ru­(bpy)₃Cl₂ as a photocatalyst. Our investigations into the origins of this unexpected additive effect have demonstrated that the carbon–carbon bond-forming step is accelerated by TFA and is a rare example of Brønsted acid catalysis in radical addition reactions. Moreover, a significant conclusion arising from these studies is the finding that product formation is dominated by radical chain processes and not by photocatalyst turnover. Together, these findings have important implications for the future design and mechanistic evaluation of photocatalytic radical processses

Radical Cation Cycloadditions Using Cleavable Redox Auxiliaries

The incorporation of an easily oxidized arylsulfide moiety facilitates the photocatalytic generation of alkene radical cations that undergo a variety of cycloaddition reactions with electron-rich reaction partners. The sulfide moiety can subsequently be reductively cleaved in a traceless fashion, affording products that are not otherwise directly accessible using photoredox catalysis. This approach constitutes a novel oxidative “redox auxiliary” strategy that offers a practical means to circumvent a fundamental thermodynamic limitation facing photoredox reactions

Enantioselective Conjugate Additions of α‑Amino Radicals via Cooperative Photoredox and Lewis Acid Catalysis

We report the highly enantioselective addition of photogenerated α-amino radicals to Michael acceptors. This method features a dual-catalyst protocol that combines transition metal photoredox catalysis with chiral Lewis acid catalysis. The combination of these two powerful modes of catalysis provides an effective, general strategy to generate and control the reactivity of photogenerated reactive intermediates

Enantioselective Conjugate Additions of α‑Amino Radicals via Cooperative Photoredox and Lewis Acid Catalysis

We report the highly enantioselective addition of photogenerated α-amino radicals to Michael acceptors. This method features a dual-catalyst protocol that combines transition metal photoredox catalysis with chiral Lewis acid catalysis. The combination of these two powerful modes of catalysis provides an effective, general strategy to generate and control the reactivity of photogenerated reactive intermediates

Enantioselective Conjugate Additions of α‑Amino Radicals via Cooperative Photoredox and Lewis Acid Catalysis

We report the highly enantioselective addition of photogenerated α-amino radicals to Michael acceptors. This method features a dual-catalyst protocol that combines transition metal photoredox catalysis with chiral Lewis acid catalysis. The combination of these two powerful modes of catalysis provides an effective, general strategy to generate and control the reactivity of photogenerated reactive intermediates